Keytruda and Keytruda Qlex, Plus Paclitaxel ± Bevacizumab, Approved for Certain Adults with PD-L1+ (CPS ≥1) Platinum-Resistant Ovarian Carcinoma

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RAHWAY, N.J.--(BUSINESS WIRE) February 11, 2026 -- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the U.S. Food and Drug Administration (FDA) approved Keytruda (pembrolizumab) and Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) plus paclitaxel, with or without bevacizumab, for the treatment of adults with PD-L1+ (Combined Positive Score [CPS] ≥1), as determined by an FDA-authorized test, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal carcinoma, who have received one or two prior systemic treatment regimens.

  • Keytruda and Keytruda Qlex are the first and only PD-1 inhibitors approved for adults with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal carcinoma with PD-L1+ tumors
  • Approvals based on Phase 3 KEYNOTE-B96 trial that demonstrated the Keytruda regimen reduced the risk of disease progression or death by 28% and reduced the risk of death by 24% compared to placebo plus paclitaxel with or without bevacizumab

    • These approvals are based on data from the Phase 3 KEYNOTE-B96 trial (also known as ENGOT-ov65), which were presented at the 2025 European Society for Medical Oncology (ESMO) Congress. Results from the trial showed that Keytruda plus paclitaxel, with or without bevacizumab, demonstrated a statistically significant improvement in progression-free survival (PFS), reducing the risk of disease progression or death by 28% (HR=0.72 [95% CI, 0.58-0.89]; p=0.0014) in patients with platinum-resistant recurrent ovarian cancer whose tumors express PD-L1 (CPS ≥1) when compared to placebo plus paclitaxel with or without bevacizumab. In this same population, the Keytruda regimen also demonstrated a statistically significant improvement in overall survival (OS), reducing the risk of death by 24% (HR=0.76 [95% CI, 0.61-0.94]; p=0.0053) compared to placebo plus paclitaxel with or without bevacizumab. The effectiveness of Keytruda Qlex for its approved indications has been established based upon evidence from the adequate and well-controlled studies conducted with Keytruda and additional data from MK-3475A-D77 comparing the pharmacokinetic, efficacy, and safety profiles of Keytruda Qlex and Keytruda.

    “For many patients with ovarian cancer, the disease can become platinum-resistant, at which point recurrence is not just a setback — it’s when options can become limited, and the reality patients face can change very quickly,” said Dr. Bradley Monk, gynecologic oncologist and medical director of the Late-Stage Clinical Research Program at Florida Cancer Specialists and Research Institute. “For patients who have been previously treated with standard platinum-based therapies, the FDA approvals of these pembrolizumab-based regimens offer the possibility of more time.”

    Keytruda Qlex is contraindicated in patients with known hypersensitivity to berahyaluronidase alfa, hyaluronidase or to any of its excipients. Keytruda and Keytruda Qlex are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions in any or multiple organs, which can occur during or after treatment, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, other transplant (including corneal graft) rejection; severe and life-threatening infusion or injection-related reactions; fatal and other serious complications in patients who receive allogeneic hematopoietic stem cell transplantation before or after beginning treatment; embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Keytruda or Keytruda Qlex is added to a thalidomide analogue plus dexamethasone, which is not recommended outside of controlled trials. Immune-mediated adverse reactions listed here may not include all such possible severe or fatal reactions. For more information, see “Selected Important Safety Information” below.

    “Historically, the prognosis has been poor for patients living with platinum-resistant recurrent ovarian cancer who have limited treatment options that may reduce the risk of disease progression or death. These approvals mark an important moment for the ovarian cancer community, reflecting years of focused investment in Keytruda,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. “Introducing the first PD-1 inhibitors for platinum-resistant ovarian cancer means we’re expanding what’s possible for patients facing this disease. It also reinforces our commitment to advancing innovative therapies and improved outcomes across women’s cancers, where the need is greatest.”

    In patients whose tumors express PD-L1 (CPS ≥1), the median PFS was 8.3 months (95% CI, 7.0-9.4) for those receiving Keytruda plus paclitaxel, with or without bevacizumab, versus 7.2 months (95% CI, 6.2-8.1) for those receiving placebo plus paclitaxel with or without bevacizumab. The median OS for these patients receiving the Keytruda regimen was 18.2 months (95% CI, 15.3-21.0) versus 14.0 months (95% CI, 12.5-16.1) for those receiving the placebo regimen.

    Of the 643 enrolled patients, 72% of patients had tumors expressing PD-L1 (CPS ≥1), 73% received bevacizumab in the study, and 46% received prior bevacizumab. A total of 47% had a platinum-free interval of less than 3 months. Patients were enrolled regardless of PD-L1 tumor expression status.

    The safety of Keytruda in combination with paclitaxel with or without bevacizumab was evaluated in 463 patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 (CPS ≥1) enrolled in KEYNOTE-B96. The median duration of exposure to Keytruda was 7.4 months (range 1 day to 35.9 months).

    Serious adverse reactions occurred in 54% of patients receiving Keytruda and paclitaxel with or without bevacizumab. Serious adverse reactions in ≥2% of patients were pneumonia (4.3%), urinary tract infection (3.9%), adrenal insufficiency (3%), hyponatremia (3%), COVID-19 (2.6%), decreased neutrophil count (2.6%), pulmonary embolism (2.6%), abdominal pain (2.1%), anemia (2.1%), colitis (2.1%), diarrhea (2.1%), febrile neutropenia (2.1%), pyrexia (2.1%) and vomiting (2.1%).

    Fatal adverse reactions occurred in 3.9% of patients receiving Keytruda and paclitaxel with or without bevacizumab, including assisted suicide (0.9%), death (0.4%), intestinal perforation (0.4%), sepsis (0.4%), COVID-19 (0.4%), cardio-respiratory arrest (0.4%), colitis (0.4%), and embolic stroke (0.4%).

    Keytruda was permanently discontinued for adverse reactions in 16% of patients. The most common adverse reactions resulting in permanent discontinuation of Keytruda (≥1%) were, colitis (1.3%), and increased alanine aminotransferase (1.3%). Adverse reactions leading to the interruption of Keytruda occurred in 44% of patients. The most common adverse events leading to interruption of Keytruda in ≥2% were urinary tract infection (3.9%), adrenal insufficiency (2.6%), pyrexia (2.6%), pneumonitis (2.6%), upper respiratory tract infection (2.6%), neutropenia (2.1%), diarrhea (2.1%) and COVID-19 (2.1%).

    The most common (≥20%) adverse reactions for patients treated with Keytruda in combination with paclitaxel with or without bevacizumab were: diarrhea (45%), fatigue (43%), nausea (41%), alopecia (38%), peripheral neuropathy (38%), epistaxis (31%), urinary tract infection (27%), constipation (25%), abdominal pain (24%), decreased appetite (24%), vomiting (24%), hypothyroidism (21%), cough (20%), hypertension (20%), and rash (20%). The most common (≥20%) laboratory abnormalities worsening from baseline were: anemia (85%), leukopenia (82%), decreased neutrophil count (71%), lymphopenia (60%), hypoalbuminemia (50%), hyponatremia (53%), hypomagnesemia (45%), increased aspartate aminotransferase (43%), increased alanine aminotransferase (40%), hypocalcemia (40%), increased alkaline phosphatase (31%), increased creatinine (29%), hypokalemia (27%) and neutropenia (21%).

    For patients treated with Keytruda in combination with paclitaxel and bevacizumab (N=169), decreased white blood cell count (27%), stomatitis (22%) and pyrexia (21%) were also reported as adverse reactions.

    About KEYNOTE-B96/ENGOT-ov65KEYNOTE-B96, also known as ENGOT-ov65, is a multicenter, randomized, double-blind placebo-controlled Phase 3 trial (ClinicalTrials.gov, NCT05116189) sponsored by Merck and conducted in collaboration with the European Network for Gynecologic Oncology Trial (ENGOT) groups investigating Keytruda, Merck’s anti-PD-1 therapy, in combination with chemotherapy (paclitaxel), with or without bevacizumab, compared to placebo plus paclitaxel, with or without bevacizumab, for the treatment of platinum-resistant recurrent ovarian cancer. The primary endpoint is PFS, as assessed by investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), and OS is a key secondary endpoint. The trial enrolled 643 patients with epithelial ovarian, fallopian tube or primary peritoneal carcinoma who received one or two prior lines of systemic therapy for ovarian carcinoma, including at least one line of platinum-based chemotherapy.

    All study medications were administered as an intravenous infusion. Keytruda 400 mg or placebo were administered on Day 1 of each 6-week treatment cycle and paclitaxel 80 mg/m2 was administered on Days 1, 8, and 15 of each 3-week treatment cycle. The option to use bevacizumab was by investigator choice prior to randomization. Bevacizumab 10 mg/kg was administered on Day 1 of a 2-week treatment cycle. Treatment with Keytruda continued until RECIST v1.1-defined progression of disease, unacceptable toxicity or a maximum of 24 months. Administration of Keytruda was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. Assessment of tumor status was performed every 9 weeks for the first year, followed by every 12 weeks thereafter.

    About platinum-resistant ovarian cancerOvarian cancer often begins in the fallopian tubes or the ovaries. As of 2022, it is the eighth most commonly diagnosed cancer and the eighth leading cause of cancer death among women worldwide. In the U.S., it is estimated there will be approximately 21,010 patients diagnosed with ovarian cancer and about 12,450 deaths from the disease in 2026. Over 80% of patients diagnosed with ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens. Approximately 25% of these patients develop resistance within six months of completing first-line platinum-based chemotherapy – defined as primary platinum-resistant ovarian cancer. Prognosis is particularly poor for these patients and approved treatment options are limited.

    About Keytruda® (pembrolizumab) injection for intravenous use, 100 mgKeytruda is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

    Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying Keytruda across a wide variety of cancers and treatment settings. The Keytruda clinical program seeks to understand the role of Keytruda across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with Keytruda, including exploring several different biomarkers.

    About Keytruda Qlex™ (pembrolizumab and berahyaluronidase alfa-pmph) injection for subcutaneous useKeytruda Qlex is a fixed-combination drug product of pembrolizumab and berahyaluronidase alfa. Pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody and berahyaluronidase alfa enhances dispersion and permeability to enable subcutaneous administration of pembrolizumab. Keytruda Qlex is administered as a subcutaneous injection into the thigh or abdomen, avoiding the 5 cm area around the navel, over one minute every three weeks (2.4 mL) or over two minutes every six weeks (4.8 mL).

    Selected Keytruda® (pembrolizumab) and Keytruda Qlex™ (pembrolizumab and berahyaluronidase alfa-pmph) Indications in the U.S.Ovarian CancerKeytruda and Keytruda Qlex are each indicated, in combination with paclitaxel, with or without bevacizumab, for the treatment of adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-authorized test, and who have received 1 or 2 prior systemic treatment regimens.

    See additional selected Keytruda and Keytruda Qlex indications in the U.S. after the Selected Important Safety Information.

    Selected Important Safety Information for Keytruda and Keytruda QlexContraindicationsKeytruda Qlex is contraindicated in patients with known hypersensitivity to berahyaluronidase alfa, hyaluronidase or to any of its excipients.

    Severe and Fatal Immune-Mediated Adverse ReactionsKeytruda and Keytruda Qlex are monoclonal antibodies that belong to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

    Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with Keytruda or Keytruda Qlex in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

    Withhold or permanently discontinue Keytruda and Keytruda Qlex depending on severity of the immune-mediated adverse reaction. In general, if Keytruda and Keytruda Qlex require interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

    Immune-Mediated PneumonitisKeytruda and Keytruda Qlex can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving Keytruda, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of Keytruda in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated Keytruda after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients. Immune-mediated pneumonitis occurred in 5% (13/251) of patients receiving Keytruda Qlex in combination with chemotherapy, including fatal (0.4%), Grade 3 (2%), and Grade 2 (1.2%) adverse reactions.

    Pneumonitis occurred in 7% (41/580) of adult patients with resected NSCLC who received Keytruda as a single agent for adjuvant treatment of NSCLC, including fatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions. Patients received high-dose corticosteroids for a median duration of 10 days (range: 1 day to 2.3 months). Pneumonitis led to discontinuation of Keytruda in 26 (4.5%) of patients. Of the patients who developed pneumonitis, 54% interrupted Keytruda, 63% discontinued Keytruda, and 71% had resolution.

    Immune-Mediated ColitisKeytruda and Keytruda Qlex can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.

    Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving Keytruda, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of Keytruda in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated Keytruda after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients. Immune-mediated colitis occurred in 1.2% (3/251) of patients receiving Keytruda Qlex in combination with chemotherapy, including Grade 3 (0.8%) and Grade 2 (0.4%) adverse reactions.

    Hepatotoxicity and Immune-Mediated HepatitisKeytruda and Keytruda Qlex can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving Keytruda, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of Keytruda in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated Keytruda after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients. Immune-mediated hepatitis occurred in 0.4% (1/251) of patients receiving Keytruda Qlex in combination with chemotherapy, including Grade 2 (0.4%) adverse reactions.

    Keytruda With Axitinib or Keytruda Qlex With AxitinibKeytruda and Keytruda Qlex, when either is used in combination with axitinib, can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt Keytruda and axitinib or Keytruda Qlex and axitinib, and consider administering corticosteroids as needed.

    With the combination of Keytruda and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to Keytruda alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT ≥3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either Keytruda (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT ≥3 times ULN was observed in 1 patient receiving Keytruda, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT ≥3 ULN subsequently recovered from the event.

    Immune-Mediated EndocrinopathiesAdrenal InsufficiencyKeytruda and Keytruda Qlex can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold Keytruda and Keytruda Qlex depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving Keytruda, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of Keytruda in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated Keytruda after symptom improvement. Adrenal insufficiency occurred in 2% (5/251) of patients receiving Keytruda Qlex in combination with chemotherapy, including Grade 3 (0.4%) and Grade 2 (0.8%) adverse reactions.

    HypophysitisKeytruda and Keytruda Qlex can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue Keytruda and Keytruda Qlex depending on severity.

    Hypophysitis occurred in 0.6% (17/2799) of patients receiving Keytruda, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of Keytruda in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated Keytruda after symptom improvement.

    Thyroid DisordersKeytruda and Keytruda Qlex can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue Keytruda and Keytruda Qlex depending on severity.

    Thyroiditis occurred in 0.6% (16/2799) of patients receiving Keytruda, including Grade 2 (0.3%). None discontinued, but Keytruda was withheld in <0.1% (1) of patients.

    Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving Keytruda, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of Keytruda in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated Keytruda after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving Keytruda, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of Keytruda in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated Keytruda after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving Keytruda as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hyperthyroidism was higher in 580 patients with resected NSCLC, occurring in 11% of patients receiving Keytruda as a single agent as adjuvant treatment, including Grade 3 (0.2%) hyperthyroidism. The incidence of new or worsening hypothyroidism was higher in 580 patients with resected NSCLC, occurring in 22% of patients receiving Keytruda as a single agent as adjuvant treatment (KEYNOTE-091), including Grade 3 (0.3%) hypothyroidism.

    Thyroiditis occurred in 0.4% (1/251) of patients receiving Keytruda Qlex in combination with chemotherapy, including Grade 2 (0.4%). Hyperthyroidism occurred in 8% (20/251) of patients receiving Keytruda Qlex in combination with chemotherapy, including Grade 2 (3.2%). Hypothyroidism occurred in 14% (35/251) of patients receiving Keytruda Qlex in combination with chemotherapy, including Grade 2 (11%).

    Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic KetoacidosisMonitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold Keytruda and Keytruda Qlex depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving Keytruda. It led to permanent discontinuation in <0.1% (1) and withholding of Keytruda in <0.1% (1) of patients. All patients who were withheld reinitiated Keytruda after symptom improvement. Type 1 DM occurred in 0.4% (1/251) of patients receiving Keytruda Qlex in combination with chemotherapy.

    Immune-Mediated Nephritis With Renal DysfunctionKeytruda and Keytruda Qlex can cause immune-mediated nephritis.

    Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving Keytruda, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of Keytruda in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated Keytruda after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

    Immune-Mediated Dermatologic Adverse ReactionsKeytruda and Keytruda Qlex can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with anti–PD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue Keytruda and Keytruda Qlex depending on severity.

    Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving Keytruda, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of Keytruda in 0.6% (16) of patients. All patients who were withheld reinitiated Keytruda after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients. Immune-mediated dermatologic adverse reactions occurred in 1.6% (4/251) of patients receiving Keytruda Qlex in combination with chemotherapy, including Grade 4 (0.8%) and Grade 3 (0.8%) adverse reactions.

    Other Immune-Mediated Adverse ReactionsThe following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received Keytruda, Keytruda Qlex, or were reported with the use of other anti–PD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis (2.8%), duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection.

    Hypersensitivity and Infusion- or Administration-Related ReactionsKeytruda and Keytruda Qlex can cause severe or life-threatening administration-related reactions, including hypersensitivity and anaphylaxis. With Keytruda and Keytruda Qlex, monitor for signs and symptoms of infusion- and administration-related systemic reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. Infusion-related reactions have been reported in 0.2% of 2799 patients receiving Keytruda. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue Keytruda. Hypersensitivity and administration related systemic reactions occurred in 3.2% (8/251) of patients receiving Keytruda Qlex in combination with platinum doublet chemotherapy, including Grade 2 (2.8%). Interrupt injection (if not already fully administered) and resume if symptoms resolve for mild or moderate systemic reactions. For severe or life-threatening systemic reactions, stop injection and permanently discontinue Keytruda Qlex.

    Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after anti–PD-1/PD-L1 treatments. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between anti–PD-1/PD-L1 treatments and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using anti–PD-1/PD-L1 treatments prior to or after an allogeneic HSCT.

    Increased Mortality in Patients With Multiple MyelomaIn trials in patients with multiple myeloma, the addition of Keytruda to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an anti–PD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.

    Embryofetal ToxicityBased on their mechanism of action, Keytruda and Keytruda Qlex can each cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating Keytruda or Keytruda Qlex and advise them to use effective contraception during treatment and for 4 months after the last dose.

    Adverse ReactionsIn study MK-3475A-D77, when Keytruda Qlex was administered with chemotherapy in metastatic non–small cell lung cancer (NSCLC), serious adverse reactions occurred in 39% of patients. Serious adverse reactions in ≥1% of patients who received Keytruda Qlex were pneumonia (10%), thrombocytopenia (4%), febrile neutropenia (4%), neutropenia (2.8%), musculoskeletal pain (2%), pneumonitis (2%), diarrhea (1.6%), rash (1.2%), respiratory failure (1.2%), and anemia (1.2%). Fatal adverse reactions occurred in 10% of patients including pneumonia (3.2%), neutropenic sepsis (2%), death not otherwise specified (1.6%), respiratory failure (1.2%), parotitis (0.4%), pneumonitis (0.4%), pneumothorax (0.4%), pulmonary embolism (0.4%), neutropenic colitis (0.4%), and seizure (0.4%). Keytruda Qlex was permanently discontinued due to an adverse reaction in 16% of 251 patients. Adverse reactions which resulted in permanent discontinuation of Keytruda Qlex in ≥2% of patients included pneumonia and pneumonitis. Dosage interruptions of Keytruda Qlex due to an adverse reaction occurred in 45% of patients. Adverse reactions which required dosage interruption in ≥2% of patients included neutropenia, anemia, thrombocytopenia, pneumonia, rash, and increased aspartate aminotransferase. The most common adverse reactions (≥20%) were nausea (25%), fatigue (25%), and musculoskeletal pain (21%).

    In KEYNOTE-006, Keytruda was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (≥20%) with Keytruda were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

    In KEYNOTE-054, when Keytruda was administered as a single agent to patients with stage III melanoma, Keytruda was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (≥1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving Keytruda. The most common adverse reaction (≥20%) with Keytruda was diarrhea (28%). In KEYNOTE-716, when Keytruda was administered as a single agent to patients with stage IIB or IIC melanoma, adverse reactions occurring in patients with stage IIB or IIC melanoma were similar to those occurring in 1011 patients with stage III melanoma from KEYNOTE-054.

    In KEYNOTE-189, when Keytruda was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, Keytruda was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of Keytruda were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (≥20%) with Keytruda were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

    In KEYNOTE-407, when Keytruda was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, Keytruda was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the Keytruda and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

    In KEYNOTE-042, Keytruda was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (≥20%) was fatigue (25%).

    In KEYNOTE-010, Keytruda monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

    In KEYNOTE-671, adverse reactions occurring in patients with resectable NSCLC receiving Keytruda in combination with platinum-containing chemotherapy, given as neoadjuvant treatment and continued as single-agent adjuvant treatment, were generally similar to those occurring in patients in other clinical trials across tumor types receiving Keytruda in combination with chemotherapy.

    The most common adverse reactions (reported in ≥20%) in patients receiving Keytruda in combination with chemotherapy or chemoradiotherapy were fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia, myalgia, insomnia, palmar-plantar erythrodysesthesia, urinary tract infection, hypothyroidism, radiation skin injury, dysphagia, dry mouth, and musculoskeletal pain.

    In the neoadjuvant phase of KEYNOTE-671, when Keytruda was administered in combination with platinum-containing chemotherapy as neoadjuvant treatment, serious adverse reactions occurred in 34% of 396 patients. The most frequent (≥2%) serious adverse reactions were pneumonia (4.8%), venous thromboembolism (3.3%), and anemia (2%). Fatal adverse reactions occurred in 1.3% of patients, including death due to unknown cause (0.8%), sepsis (0.3%), and immune-mediated lung disease (0.3%). Permanent discontinuation of any study drug due to an adverse reaction occurred in 18% of patients who received Keytruda in combination with platinum-containing chemotherapy; the most frequent adverse reactions (≥1%) that led to permanent discontinuation of any study drug were acute kidney injury (1.8%), interstitial lung disease (1.8%), anemia (1.5%), neutropenia (1.5%), and pneumonia (1.3%).

    Of the Keytruda-treated patients who received neoadjuvant treatment, 6% of 396 patients did not receive surgery due to adverse reactions. The most frequent (≥1%) adverse reaction that led to cancellation of surgery in the Keytruda arm was interstitial lung disease (1%).

    In the adjuvant phase of KEYNOTE-671, when Keytruda was administered as a single agent as adjuvant treatment, serious adverse reactions occurred in 14% of 290 patients. The most frequent serious adverse reaction was pneumonia (3.4%). One fatal adverse reaction of pulmonary hemorrhage occurred. Permanent discontinuation of Keytruda due to an adverse reaction occurred in 12% of patients who received Keytruda as a single agent, given as adjuvant treatment; the most frequent adverse reactions (≥1%) that led to permanent discontinuation of Keytruda were diarrhea (1.7%), interstitial lung disease (1.4%), increased aspartate aminotransferase (1%), and musculoskeletal pain (1%).

    Adverse reactions observed in KEYNOTE-091 were generally similar to those occurring in other patients with NSCLC receiving Keytruda as a single agent, with the exception of hypothyroidism (22%), hyperthyroidism (11%), and pneumonitis (7%). Two fatal adverse reactions of myocarditis occurred.

    Adverse reactions observed in KEYNOTE-483 were generally similar to those occurring in other patients receiving Keytruda in combination with pemetrexed and platinum chemotherapy.

    In KEYNOTE-689, the most common adverse reactions (≥20%) in patients receiving Keytruda were stomatitis (48%), radiation skin injury (40%), weight loss (36%), fatigue (33%), dysphagia (29%), constipation (27%), hypothyroidism (26%), nausea (24%), rash (22%), dry mouth (22%), diarrhea (22%), and musculoskeletal pain (22%).

    In the neoadjuvant phase of KEYNOTE-689, of the 361 patients who received at least one dose of single agent Keytruda, 11% experienced serious adverse reactions. Serious adverse reactions that occurred in more than one patient were pneumonia (1.4%), tumor hemorrhage (0.8%), dysphagia (0.6%), immune-mediated hepatitis (0.6%), cellulitis (0.6%), and dyspnea (0.6%). Fatal adverse reactions occurred in 1.1% of patients, including respiratory failure, clostridium infection, septic shock, and myocardial infarction (one patient each). Permanent discontinuation of Keytruda due to an adverse reaction occurred in 2.8% of patients who received Keytruda as neoadjuvant treatment. The most frequent adverse reaction which resulted in permanent discontinuation of neoadjuvant Keytruda in more than one patient was arthralgia (0.6%).

    Of the 361 patients who received Keytruda as neoadjuvant treatment, 11% did not receive surgery. Surgical cancellation on the Keytruda arm was due to disease progression in 4%, patient decision in 3%, adverse reactions in 1.4%, physician’s decision in 1.1%, unresectable tumor in 0.6%, loss of follow-up in 0.3%, and use of non-study anti-cancer therapy in 0.3%.

    Of the 323 Keytruda-treated patients who received surgery following the neoadjuvant phase, 1.2% experienced delay of surgery (defined as on-study surgery occurring ≥9 weeks after initiation of neoadjuvant Keytruda) due to adverse reactions, and 2.8% did not receive adjuvant treatment due to adverse reactions.

    In the adjuvant phase of KEYNOTE-689, of the 255 patients who received at least one dose of Keytruda, 38% experienced serious adverse reactions. The most frequent serious adverse reactions reported in ≥1% of Keytruda-treated patients were pneumonia (2.7%), pyrexia (2.4%), stomatitis (2.4%), acute kidney injury (2.0%), pneumonitis (1.6%), COVID-19 (1.2%), death not otherwise specified (1.2%), diarrhea (1.2%), dysphagia (1.2%), gastrostomy tube site complication (1.2%), and immune-mediated hepatitis (1.2%). Fatal adverse reactions occurred in 5% of patients, including death not otherwise specified (1.2%), acute renal failure (0.4%), hypercalcemia (0.4%), pulmonary hemorrhage (0.4%), dysphagia/malnutrition (0.4%), mesenteric thrombosis (0.4%), sepsis (0.4%), pneumonia (0.4%), COVID-19 (0.4%), respiratory failure (0.4%), cardiovascular disorder (0.4%), and gastrointestinal hemorrhage (0.4%). Permanent discontinuation of adjuvant Keytruda due to an adverse reaction occurred in 17% of patients. The most frequent (≥1%) adverse reactions that led to permanent discontinuation of adjuvant Keytruda were pneumonitis, colitis, immune-mediated hepatitis, and death not otherwise specified.

    In KEYNOTE-048, Keytruda monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (≥20%) were fatigue (33%), constipation (20%), and rash (20%).

    In KEYNOTE-048, when Keytruda was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, Keytruda was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of Keytruda were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (≥20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

    In KEYNOTE-012, Keytruda was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (≥20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received Keytruda as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

    In KEYNOTE-A39, when Keytruda was administered in combination with enfortumab vedotin to patients with locally advanced or metastatic urothelial cancer (n=440), fatal adverse reactions occurred in 3.9% of patients, including acute respiratory failure (0.7%), pneumonia (0.5%), and pneumonitis/ILD (0.2%). Serious adverse reactions occurred in 50% of patients receiving Keytruda in combination with enfortumab vedotin; the serious adverse reactions in ≥2% of patients were rash (6%), acute kidney injury (5%), pneumonitis/ILD (4.5%), urinary tract infection (3.6%), diarrhea (3.2%), pneumonia (2.3%), pyrexia (2%), and hyperglycemia (2%). Permanent discontinuation of Keytruda occurred in 27% of patients. The most common adverse reactions (≥2%) resulting in permanent discontinuation of Keytruda were pneumonitis/ILD (4.8%) and rash (3.4%). The most common adverse reactions (≥20%) occurring in patients treated with Keytruda in combination with enfortumab vedotin were rash (68%), peripheral neuropathy (67%), fatigue (51%), pruritus (41%), diarrhea (38%), alopecia (35%), weight loss (33%), decreased appetite (33%), nausea (26%), constipation (26%), dry eye (24%), dysgeusia (21%), and urinary tract infection (21%).

    In KEYNOTE-052, Keytruda was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. Serious adverse reactions occurred in 42% of patients; those ≥2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (≥20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).

    In KEYNOTE-045, Keytruda was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of Keytruda was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of Keytruda-treated patients; those ≥2% were urinary tract infection, pneumonia, anemia, and pneumonitis. The most common adverse reactions (≥20%) in patients who received Keytruda were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

    In KEYNOTE-905, the most common adverse reactions (≥20%) occurring in cisplatin-ineligible patients with MIBC treated with Keytruda in combination with enfortumab vedotin (n=167) were rash (54%), pruritus (47%), fatigue (47%), peripheral neuropathy (39%), alopecia (35%), dysgeusia (35%), diarrhea (34%), constipation (28%), decreased appetite (28%), nausea (26%), urinary tract infection (24%), dry eye (21%), and weight loss (20%).

    In the neoadjuvant phase of KEYNOTE-905, serious adverse reactions occurred in 27% (n=167) of patients; the most frequent (≥2%) were urinary tract infection (3.6%) and hematuria (2.4%). Fatal adverse reactions occurred in 1.2% of patients, including myasthenia gravis and toxic epidermal necrolysis (0.6% each). Additional fatal adverse reactions were reported in 2.7% of patients in the post-surgery phase before adjuvant treatment started, including sepsis and intestinal obstruction (1.4% each). Permanent discontinuation of Keytruda due to an adverse reaction occurred in 15% of patients; the most frequent (>1%) were rash (2.4%, including generalized exfoliative dermatitis), increased alanine aminotransferase, increased aspartate aminotransferase, diarrhea, dysgeusia, and toxic epidermal necrolysis (1.2% each). Of the 167 patients in the Keytruda in combination with enfortumab vedotin arm who received neoadjuvant treatment, 7 (4.2%) patients did not receive surgery due to adverse reactions. The adverse reactions that led to cancellation of surgery were acute myocardial infarction, bile duct cancer, colon cancer, respiratory distress, urinary tract infection, and two deaths due to myasthenia gravis and toxic epidermal necrolysis (0.6% each).

    Of the 146 patients who received neoadjuvant treatment with Keytruda in combination with enfortumab vedotin and underwent radical cystectomy, 6 (4.1%) patients experienced delay of surgery (defined as time from last neoadjuvant treatment to surgery exceeding 8 weeks) due to adverse reactions.

    In the adjuvant phase of KEYNOTE-905, serious adverse reactions occurred in 43% (n=100) of patients; the most frequent (≥2%) were urinary tract infection (8%); acute kidney injury and pyelonephritis (5% each); urosepsis (4%); and hypokalemia, intestinal obstruction, and sepsis (2% each). Fatal adverse reactions occurred in 7% of patients, including urosepsis, intracranial hemorrhage, death, myocardial infarction, multiple organ dysfunction syndrome, and pseudomonal pneumonia (1% each). Permanent discontinuation of Keytruda due to an adverse reaction occurred in 28% of patients; the most frequent (>1%) were diarrhea (5%), peripheral neuropathy, acute kidney injury, and pneumonitis (2% each).

    In KEYNOTE-057, Keytruda was discontinued due to adverse reactions in 11% of 148 patients with high-risk NMIBC. The most common adverse reaction resulting in permanent discontinuation of Keytruda was pneumonitis (1.4%). Serious adverse reactions occurred in 28% of patients; those ≥2% were pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract infection (2%). The most common adverse reactions (≥20%) were fatigue (29%), diarrhea (24%), and rash (24%).

    Adverse reactions occurring in patients with MSI-H or dMMR CRC were similar to those occurring in patients with melanoma or NSCLC who received Keytruda as a monotherapy.

    In KEYNOTE-158 and KEYNOTE-164, adverse reactions occurring in patients with MSI-H or dMMR cancer were similar to those occurring in patients with other solid tumors who received Keytruda as a single agent.

    In KEYNOTE-811, fatal adverse reactions occurred in 3 patients who received Keytruda in combination with trastuzumab and CAPOX (capecitabine plus oxaliplatin) or FP (5-FU plus cisplatin) and included pneumonitis in 2 patients and hepatitis in 1 patient. Keytruda was discontinued due to adverse reactions in 13% of 350 patients with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma. Adverse reactions resulting in permanent discontinuation of Keytruda in ≥1% of patients were pneumonitis (2.0%) and pneumonia (1.1%). In the Keytruda arm vs placebo, there was a difference of ≥5% incidence between patients treated with Keytruda vs standard of care for diarrhea (53% vs 47%), rash (35% vs 28%), hypothyroidism (11% vs 5%), and pneumonia (11% vs 5%).

    In KEYNOTE-859, when Keytruda was administered in combination with fluoropyrimidine- and platinum-containing chemotherapy, serious adverse reactions occurred in 45% of 785 patients. Serious adverse reactions in >2% of patients included pneumonia (4.1%), diarrhea (3.9%), hemorrhage (3.9%), and vomiting (2.4%). Fatal adverse reactions occurred in 8% of patients who received Keytruda, including infection (2.3%) and thromboembolism (1.3%). Keytruda was permanently discontinued due to adverse reactions in 15% of patients. The most common adverse reactions resulting in permanent discontinuation of Keytruda (≥1%) were infections (1.8%) and diarrhea (1.0%). The most common adverse reactions (reported in ≥20%) in patients receiving Keytruda in combination with chemotherapy were peripheral neuropathy (47%), nausea (46%), fatigue (40%), diarrhea (36%), vomiting (34%), decreased appetite (29%), abdominal pain (26%), palmar-plantar erythrodysesthesia syndrome (25%), constipation (22%), and weight loss (20%).

    In KEYNOTE-590, when Keytruda was administered with cisplatin and fluorouracil to patients with metastatic or locally advanced esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma who were not candidates for surgical resection or definitive chemoradiation, Keytruda was discontinued due to adverse reactions in 15% of 370 patients. The most common adverse reactions resulting in permanent discontinuation of Keytruda (≥1%) were pneumonitis (1.6%), acute kidney injury (1.1%), and pneumonia (1.1%). The most common adverse reactions (≥20%) with Keytruda in combination with chemotherapy were nausea (67%), fatigue (57%), decreased appetite (44%), constipation (40%), diarrhea (36%), vomiting (34%), stomatitis (27%), and weight loss (24%).

    Adverse reactions occurring in patients with esophageal cancer who received Keytruda as a monotherapy were similar to those occurring in patients with melanoma or NSCLC who received Keytruda as a monotherapy.

    In KEYNOTE-A18, when Keytruda was administered with CRT (cisplatin plus external beam radiation therapy [EBRT] followed by brachytherapy [BT]) to patients with FIGO 2014 Stage III-IVA cervical cancer, fatal adverse reactions occurred in 1.4% of 294 patients, including 1 case each (0.3%) of large intestinal perforation, urosepsis, sepsis, and vaginal hemorrhage. Serious adverse reactions occurred in 34% of patients; those ≥1% included urinary tract infection (3.1%), urosepsis (1.4%), and sepsis (1%). Keytruda was discontinued for adverse reactions in 9% of patients. The most common adverse reaction (≥1%) resulting in permanent discontinuation was diarrhea (1%). For patients treated with Keytruda in combination with CRT, the most common adverse reactions (≥10%) were nausea (56%), diarrhea (51%), urinary tract infection (35%), vomiting (34%), fatigue (28%), hypothyroidism (23%), constipation (20%), weight loss (19%), decreased appetite (18%), pyrexia (14%), abdominal pain and hyperthyroidism (13% each), dysuria and rash (12% each), back and pelvic pain (11% each), and COVID-19 (10%).

    In KEYNOTE-826, when Keytruda was administered in combination with paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab (n=307), to patients with persistent, recurrent, or first-line metastatic cervical cancer regardless of tumor PD-L1 expression who had not been treated with chemotherapy except when used concurrently as a radio-sensitizing agent, fatal adverse reactions occurred in 4.6% of patients, including 3 cases of hemorrhage, 2 cases each of sepsis and due to unknown causes, and 1 case each of acute myocardial infarction, autoimmune encephalitis, cardiac arrest, cerebrovascular accident, femur fracture with perioperative pulmonary embolus, intestinal perforation, and pelvic infection. Serious adverse reactions occurred in 50% of patients receiving Keytruda in combination with chemotherapy with or without bevacizumab; those ≥3% were febrile neutropenia (6.8%), urinary tract infection (5.2%), anemia (4.6%), and acute kidney injury and sepsis (3.3% each).

    Keytruda was discontinued in 15% of patients due to adverse reactions. The most common adverse reaction resulting in permanent discontinuation (≥1%) was colitis (1%).

    For patients treated with Keytruda, chemotherapy, and bevacizumab (n=196), the most common adverse reactions (≥20%) were peripheral neuropathy (62%), alopecia (58%), anemia (55%), fatigue/asthenia (53%), nausea and neutropenia (41% each), diarrhea (39%), hypertension and thrombocytopenia (35% each), constipation and arthralgia (31% each), vomiting (30%), urinary tract infection (27%), rash (26%), leukopenia (24%), hypothyroidism (22%), and decreased appetite (21%).

    For patients treated with Keytruda in combination with chemotherapy with or without bevacizumab, the most common adverse reactions (≥20%) were peripheral neuropathy (58%), alopecia (56%), fatigue (47%), nausea (40%), diarrhea (36%), constipation (28%), arthralgia (27%), vomiting (26%), hypertension and urinary tract infection (24% each), and rash (22%).

    In KEYNOTE-158, Keytruda was discontinued due to adverse reactions in 8% of 98 patients with previously treated recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving Keytruda; the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (≥20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

    In KEYNOTE-394, Keytruda was discontinued due to adverse reactions in 13% of 299 patients with previously treated hepatocellular carcinoma. The most common adverse reaction resulting in permanent discontinuation of Keytruda was ascites (2.3%). The most common adverse reactions in patients receiving Keytruda (≥10%) were pyrexia (18%), rash (18%), diarrhea (16%), decreased appetite (15%), pruritus (12%), upper respiratory tract infection (11%), cough (11%), and hypothyroidism (10%).

    In KEYNOTE-966, when Keytruda was administered in combination with gemcitabine and cisplatin, Keytruda was discontinued for adverse reactions in 15% of 529 patients with locally advanced unresectable or metastatic biliary tract cancer. The most common adverse reaction resulting in permanent discontinuation of Keytruda (≥1%) was pneumonitis (1.3%). Adverse reactions leading to the interruption of Keytruda occurred in 55% of patients. The most common adverse reactions or laboratory abnormalities leading to interruption of Keytruda (≥2%) were decreased neutrophil count (18%), decreased platelet count (10%), anemia (6%), decreased white blood cell count (4%), pyrexia (3.8%), fatigue (3.0%), cholangitis (2.8%), increased ALT (2.6%), increased AST (2.5%), and biliary obstruction (2.3%).

    In KEYNOTE-017 and KEYNOTE-913, adverse reactions occurring in patients with MCC (n=105) were generally similar to those occurring in patients with melanoma or NSCLC who received Keytruda as a single agent.

    In KEYNOTE-426, when Keytruda was administered in combination with axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse reactions occurred in 40% of patients, the most frequent (≥1%) were hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse reaction occurred in 31% of patients; Keytruda only (13%), axitinib only (13%), and the combination (8%); the most common were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common adverse reactions (≥20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

    In KEYNOTE-564, when Keytruda was administered as a single agent for the adjuvant treatment of renal cell carcinoma, serious adverse reactions occurred in 20% of patients receiving Keytruda; the serious adverse reactions (≥1%) were acute kidney injury, adrenal insufficiency, pneumonia, colitis, and diabetic ketoacidosis (1% each). Fatal adverse reactions occurred in 0.2% including 1 case of pneumonia. Discontinuation of Keytruda due to adverse reactions occurred in 21% of 488 patients; the most common (≥1%) were increased ALT (1.6%), colitis (1%), and adrenal insufficiency (1%). The most common adverse reactions (≥20%) were musculoskeletal pain (41%), fatigue (40%), rash (30%), diarrhea (27%), pruritus (23%), and hypothyroidism (21%).

    In KEYNOTE-868, when Keytruda was administered in combination with chemotherapy (paclitaxel and carboplatin) to patients with advanced or recurrent endometrial carcinoma (n=382), serious adverse reactions occurred in 35% of patients receiving Keytruda in combination with chemotherapy, compared to 19% of patients receiving placebo in combination with chemotherapy (n=377). Fatal adverse reactions occurred in 1.6% of patients receiving Keytruda in combination with chemotherapy, including COVID-19 (0.5%) and cardiac arrest (0.3%). Keytruda was discontinued for an adverse reaction in 14% of patients. Adverse reactions occurring in patients treated with Keytruda and chemotherapy were generally similar to those observed with Keytruda alone or chemotherapy alone, with the exception of rash (33% all Grades; 2.9% Grades 3-4).

    Adverse reactions occurring in patients with MSI-H or dMMR endometrial carcinoma who received Keytruda as a single agent were similar to those occurring in patients with melanoma or NSCLC who received Keytruda as a single agent.

    Adverse reactions occurring in patients with TMB-H cancer were similar to those occurring in patients with other solid tumors who received Keytruda as a single agent.

    Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC were similar to those occurring in patients with melanoma or NSCLC who received Keytruda as a monotherapy.

    In KEYNOTE-522, when Keytruda was administered with neoadjuvant chemotherapy (carboplatin and paclitaxel followed by doxorubicin or epirubicin and cyclophosphamide) followed by surgery and continued adjuvant treatment with Keytruda as a single agent (n=778) to patients with newly diagnosed, previously untreated, high-risk early-stage TNBC, fatal adverse reactions occurred in 0.9% of patients, including 1 each of adrenal crisis, autoimmune encephalitis, hepatitis, pneumonia, pneumonitis, pulmonary embolism, and sepsis in association with multiple organ dysfunction syndrome and myocardial infarction. Serious adverse reactions occurred in 44% of patients receiving Keytruda; those ≥2% were febrile neutropenia (15%), pyrexia (3.7%), anemia (2.6%), and neutropenia (2.2%). Keytruda was discontinued in 20% of patients due to adverse reactions. The most common reactions (≥1%) resulting in permanent discontinuation were increased ALT (2.7%), increased AST (1.5%), and rash (1%). The most common adverse reactions (≥20%) in patients receiving Keytruda were fatigue (70%), nausea (67%), alopecia (61%), rash (52%), constipation (42%), diarrhea and peripheral neuropathy (41% each), stomatitis (34%), vomiting (31%), headache (30%), arthralgia (29%), pyrexia (28%), cough (26%), abdominal pain (24%), decreased appetite (23%), insomnia (21%), and myalgia (20%).

    In KEYNOTE-355, when Keytruda and chemotherapy (paclitaxel, paclitaxel protein-bound, or gemcitabine and carboplatin) were administered to patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting (n=596), fatal adverse reactions occurred in 2.5% of patients, including cardio-respiratory arrest (0.7%) and septic shock (0.3%). Serious adverse reactions occurred in 30% of patients receiving Keytruda in combination with chemotherapy; the serious reactions in ≥2% were pneumonia (2.9%), anemia (2.2%), and thrombocytopenia (2%). Keytruda was discontinued in 11% of patients due to adverse reactions. The most common reactions resulting in permanent discontinuation (≥1%) were increased ALT (2.2%), increased AST (1.5%), and pneumonitis (1.2%). The most common adverse reactions (≥20%) in patients receiving Keytruda in combination with chemotherapy were fatigue (48%), nausea (44%), alopecia (34%), diarrhea and constipation (28% each), vomiting and rash (26% each), cough (23%), decreased appetite (21%), and headache (20%).

    In KEYNOTE-B96, when Keytruda in combination with paclitaxel with or without bevacizumab was administered to patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors expressed PD-L1 (CPS ≥1), serious adverse reactions occurred in 54% of patients receiving Keytruda and paclitaxel with or without bevacizumab. Serious adverse reactions in ≥2% of patients were pneumonia (4.3%), urinary tract infection (3.9%), adrenal insufficiency, hyponatremia (3% each), COVID-19, decreased neutrophil count, pulmonary embolism (2.6% each), abdominal pain, anemia, colitis, diarrhea, febrile neutropenia, pyrexia, and vomiting (2.1% each).

    Fatal adverse reactions occurred in 3.9% of patients receiving Keytruda and paclitaxel with or without bevacizumab, including assisted suicide (0.9%), death, intestinal perforation, sepsis, COVID-19, cardiorespiratory arrest, colitis, and embolic stroke (0.4% each).

    Keytruda was permanently discontinued for adverse reactions in 16% of patients. The most common adverse reactions resulting in permanent discontinuation of Keytruda (≥1%) were colitis and increased alanine aminotransferase (1.3% each). Adverse reactions leading to the interruption of Keytruda occurred in 44% of patients. The most common adverse reactions leading to interruption of Keytruda in ≥2% were urinary tract infection (3.9% each), adrenal insufficiency, pyrexia, pneumonitis, upper respiratory tract infection (2.6% each), neutropenia, diarrhea, and COVID-19 (2.1% each).

    The most common adverse reactions (≥20%) for patients treated with Keytruda in combination with paclitaxel with or without bevacizumab were diarrhea (45%), fatigue (43%), nausea (41%), alopecia, peripheral neuropathy (38% each), epistaxis (31%), urina

    Posted : 2026-02-18 13:38

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