aIn 790 patients receiving single-agent KEYTRUDA first line for advanced NSCLC.
bGrades 3–4.
cIn 300 patients receiving single-agent KEYTRUDA for HNSCC.
dIn 276 patients receiving KEYTRUDA in combination with platinum and FU for HNSCC.
eIn 1,185 patients with HNSCC.
- Of 2,799 patients receiving KEYTRUDA, immune-mediated type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 6 (0.2%) patients, and thyroiditis occurred in 16 (0.6%) patients.
- Pneumonitis occurred in 17% of 790 patients with NSCLC and a history of prior thoracic radiation vs 7.7% of patients who did not receive prior thoracic radiation.
- Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy.
- KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. Grades 3 and 4 increased ALT and AST were seen in 20% and 13% of patients, respectively. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are used in monotherapy. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.
- Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.
- For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids.
- The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2,799 patients treated with KEYTRUDA: arthritis (1.5%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.
- Solid organ transplant rejection has been reported in the postmarketing setting in patients treated with KEYTRUDA.
- Severe or life-threatening infusion-related reactions have been reported in 6 (0.2%) of 2,799 patients receiving KEYTRUDA.
- Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD‑1 receptor–blocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions.
- In patients with a history of allogeneic HSCT, acute GVHD, including fatal GVHD, has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.
- In 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 a PD‑1 or PD‑L1 blocking antibody in this combination is not recommended outside of controlled trials.
ALT = alanine aminotransferase; AST = aspartate aminotransferase; cHL = classical Hodgkin lymphoma; FU = fluorouracil; HNSCC = head and neck squamous cell carcinoma; NSCLC = non–small cell lung cancer; PD‑1 = programmed death receptor-1; PD‑L1 = programmed death ligand 1; Q2W = every 2 weeks; Q3W = every 3 weeks.
aGraded per NCI CTCAE v4.0
bIncludes fatigue, asthenia
cIncludes diarrhea, colitis, hemorrhagic diarrhea, microscopic colitis
dIncludes dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis bullous, dermatitis contact, dermatitis exfoliative, drug eruption, erythema, erythema multiforme, rash, erythematous rash, generalized rash, macular rash, maculo-papular rash, pruritic rash, seborrheic dermatitis
eIncludes cough, productive cough
fIncludes dyspnea, exertional dyspnea
gIncludes pneumonia, atypical pneumonia, bacterial pneumonia, staphylococcal pneumonia, aspiration pneumonia, lower respiratory tract infection, lung infection, lung infection pseudomonal
hIncludes back pain, musculoskeletal chest pain, musculoskeletal pain, myalgia
iIncludes peripheral sensory neuropathy, peripheral neuropathy, hypoesthesia, dysesthesia
plat/FU = platinum + fluorouracil; EXTREME = cetuximab + platinum + fluorouracil.