- Safety was evaluated in 2,799 patients in 3 randomized, open-label, active-controlled clinical trials, which enrolled 912 patients with unresectable or metastatic melanoma and 682 patients with mNSCLC, and 1 single-arm trial, which enrolled 655 patients with unresectable or metastatic melanoma and 550 patients with mNSCLC.
- 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 more frequently in patients with a history of thoracic radiation (6.9%) compared to those without (2.9%).
- The incidence of new or worsening hypothyroidism was higher in patients with HNSCC, occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3 (0.5%) hypothyroidism.
- Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy.
- 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 cHL, 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 developed graft-versus-host disease (GVHD) (1 fatal case), and 2 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, and intervene promptly.
- 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 clinical 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 clinical trials.
cHL = classical Hodgkin lymphoma; HNSCC = head and neck squamous cell carcinoma; mNSCLC = metastatic NSCLC; NSCLC = non–small lung cancer; PD-1 = programmed death receptor-1; PD-L1 = programmed death ligand 1; Q2W = every 2 weeks; Q3W = every 3 weeks.
- KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL, and treatment was interrupted due to adverse reactions in 15% of patients. Twenty-five percent of patients had an adverse reaction requiring systemic corticosteroid therapy. Serious adverse reactions occurred in 26% of patients, and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment.
Musculoskeletal painb |
30 |
0 |
Upper respiratory tract infectionc |
28 |
0 |
Pyrexia |
28 |
0 |
Fatigued |
23 |
2 |
Coughe |
26 |
2 |
Dyspnea |
21 |
11 |
aGraded per NCI-CTCAE v4.0.
bIncludes arthralgia, back pain, myalgia, musculoskeletal pain, pain in extremity, musculoskeletal chest pain, bone pain, neck pain, non-cardiac chest pain.
cIncludes nasopharyngitis, pharyngitis, rhinorrhea, rhinitis, sinusitis, upper respiratory tract infection.
dIncludes fatigue, asthenia.
eIncludes allergic cough, cough, productive cough.
NCI-CTCAE = National Cancer Institute-Common Terminology Criteria for Adverse Events.
fEach test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: KEYTRUDA (range: 44 to 48 patients).
gGraded per NCI-CTCAE v4.0.
hIncludes elevation of AST or ALT.
- Pediatric patients: There is limited experience in pediatric patients. In a study, 40 pediatric patients (16 children aged 2 years to younger than 12 years and 24 adolescents aged 12 years to 18 years) with advanced melanoma, lymphoma, or PD-L1–positive advanced, relapsed, or refractory solid tumors were administered KEYTRUDA 2 mg/kg Q3W. Patients received KEYTRUDA for a median of 3 doses (range: 1–17 doses), with 34 patients (85%) for 2 doses or more. The safety profile in these pediatric patients was similar to that seen in adults treated with KEYTRUDA. Toxicities that occurred at a higher rate (≥15% difference) in these patients when compared to adults under 65 years of age were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).
AST = aspartate aminotransferase; ALT = alanine aminotransferase.