For first-line use in patients with advanced melanoma

SUPERIOR OVERALL SURVIVAL (OS) VS IPILIMUMAB

55% 2-year OS rate with KEYTRUDA1,a

Kaplan-Meier Estimates of OS1,b

Kaplan-Meier Estimates of Overall Survival: KEYTRUDA® (pembrolizumab) vs Ipilimumab Kaplan-Meier Estimates of Overall Survival: KEYTRUDA® (pembrolizumab) vs Ipilimumab

a10 mg/kg Q3W.

bResults were similar in the 2 treatment arms for KEYTRUDA.

  • Median OS was not reached with KEYTRUDA 10 mg/kg Q3W (95% CI, 23.5 months–NR) or with KEYTRUDA 10 mg/kg Q2W (22.1 months–NR). Median OS was 16.0 months with ipilimumab (95% CI, 13.5–22.0).1
  • Significant improvement in OS (HR=0.68; P<0.001) with KEYTRUDA 10 mg/kg Q3W (95% CI, 0.53–0.86) and KEYTRUDA 10 mg/kg Q2W (95% CI, 0.53–0.87) vs ipilimumab.1
    • Number of deaths observed in each arm: 119/277 (43%) and 122/279 (44%) with KEYTRUDA 10 mg/kg Q3W and Q2W, respectively, and 142/278 (51%) with ipilimumab1

Q3W Dosing With KEYTRUDA® (pembrolizumab)
Over 12 months, patients may receive 9 fewer infusions with Q3W dosing with KEYTRUDA vs Q2W dosing with nivolumab (17 vs 26, respectively).2,c
cDoes not imply comparable efficacy or safety.
cDoes not imply comparable efficacy or safety.

SUPERIOR PROGRESSION-FREE SURVIVAL (PFS)

46% 6-month PFS rate with KEYTRUDA in KEYNOTE-006 vs ipilimumab (1-year analysis)3,d

Kaplan-Meier Estimates of PFS

Kaplan-Meier Estimates of Progression-free Survival: KEYTRUDA® (pembrolizumab) vs Ipilimumab Kaplan-Meier Estimates of Progression-free Survival: KEYTRUDA® (pembrolizumab) vs Ipilimumab

dKEYTRUDA 10 mg/kg Q3W.

From The New England Journal of Medicine, Robert C, Schachter J, Long GV, et al, for the KEYNOTE-006 investigators, Pembrolizumab versus ipilimumab in advanced melanoma, Vol 372, Pages 2521–2532. Copyright © 2015 Massachusetts Medical Society.3

  • 42% reduction in the risk of disease progression or death with KEYTRUDA 10 mg/kg Q3W vs ipilimumab (HR=0.58; 95% CI, 0.47–0.72; P<0.001) and with KEYTRUDA Q2W vs ipilimumab (HR=0.58; 95% CI, 0.46–0.72; P<0.001).
    • Results based on 502 events: 157/277 (57%) and 157/279 (56%) with KEYTRUDA 10 mg/kg Q3W and Q2W, respectively, and 188/278 (68%) with ipilimumab
  • Median PFS was 4.1 months (95% CI, 2.9–6.9), 5.5 months (95% CI, 3.4–6.9), and 2.8 months (95% CI, 2.8–2.9) with KEYTRUDA 10 mg/kg Q3W, KEYTRUDA 10 mg/kg Q2W, and ipilimumab, respectively.

SUPERIOR OVERALL RESPONSE RATE (ORR)

Nearly 3 times higher ORR with KEYTRUDA vs ipilimumab in KEYNOTE-006 (1-year analysis)e

Overall Response Rates With KEYTRUDA® (pembrolizumab) vs Ipilimumab Overall Response Rates With KEYTRUDA® (pembrolizumab) vs Ipilimumab

Percentages have been rounded to the nearest integer.

eKEYTRUDA 10 mg/kg Q3W.

  • Among the 91 patients randomized to KEYTRUDA 10 mg/kg Q3W with an objective response, response durations ranged from 1.4+ to 8.1+ months.
  • 34% (n=94/279; 95% CI, 28–40) of patients responded to KEYTRUDA 10 mg/kg Q2W.
    • 5% complete response rate and 29% partial response rate with KEYTRUDA 10 mg/kg Q2W.
  • Among the 94 patients randomized to KEYTRUDA 10 mg/kg Q2W with an objective response, response durations ranged from 1.4+ to 8.2 months.

Q3W = every 3 weeks; Q2W = every 2 weeks; CI = confidence interval; NR = not reached; HR = hazard ratio.


FOR FIRST-LINE USE IN PATIENTS WITH ADVANCED MELANOMA REGARDLESS OF BRAF STATUS

APPROVED FIRST LINE based on a head-to-head trial

Pivotal Phase 3 Trial vs Ipilimumab Evaluating OS and PFS4

  • An open-label, multicenter, active-controlled trial that included patients with unresectable or metastatic melanoma with progression of disease, no prior ipilimumab, and no more than 1 prior systemic treatment for metastatic melanoma.
    • Patients with BRAF V600E mutation–positive melanoma were not required to have received prior BRAF inhibitor therapy.
KEYNOTE-006 Trial Study DesignKEYNOTE-006 Trial Study Design

fPatients were treated with ipilimumab for 4 doses unless discontinued earlier for disease progression or unacceptable toxicity.

gAs assessed by blinded independent central review using Response Evaluation Criteria In Solid Tumors 1.1.

  • Patients with disease progression could receive additional doses of KEYTRUDA unless disease progression was symptomatic, was rapidly progressive, required urgent intervention, occurred with a decline in performance status, or was confirmed at 4 to 6 weeks with repeat imaging.
  • Assessment of tumor status was performed at 12 weeks, then every 6 weeks through week 48, followed by every 12 weeks thereafter.

BRAF = B-Raf proto-oncogene, serine/threonine kinase.


STUDIED ACROSS A RANGE OF PATIENTS

Patient Characteristics in the Phase 3 Trial4,h

No prior systemic therapy
66%
BRAF mutation
36%
Normal LDH
at baseline
68%
Stage M1c
disease
65%
  • Among patients with BRAF mutation–positive melanoma:
    • 139 (46%) were previously treated with a BRAF inhibitor.
    • 161 (54%) were BRAF inhibitor–naïve.
  • The study included patients with both PD‑L1–positive and –negative melanoma, using a 1% cutoff for PD-L1 statusi:
    • 80% of patients had PD-L1–positive melanoma.
    • 18% of patients had PD-L1–negative melanoma.
    • 2% had unknown PD-L1 status.
KEYTRUDA® (pembrolizumab) for First-line Therapy or Second- or Subsequent-line Therapy for Metastatic or Unresectable Melanoma
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend pembrolizumab (KEYTRUDA) for first-line therapy (category 1) or second- or subsequent-line therapy for metastatic or unresectable melanoma (category 2A).5

hOf the 834 patients in KEYNOTE-006, 60% were male, the median age was 62 years (range: 18–89), 98% were white, 69% had an Eastern Cooperative Oncology Group performance status of 0, 68% had normal LDH, and 9% had a history of brain metastases.

iPD-L1 expression (≥1% of tumor cells [positive] vs <1% of tumor cells [negative]) according to an investigational use–only assay.

Category 1 = Based upon high-level evidence, there is uniform National Comprehensive Cancer Network® (NCCN®) consensus that the intervention is appropriate.5

Category 2A = Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.5

NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

LDH = lactate dehydrogenase; PD-L1 = programmed death ligand 1.


ALL INDICATIONS
  • ADVANCED MELANOMA:KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
  • FIRST-LINE MONOTHERAPY:KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic non–small cell lung cancer (NSCLC)NSCLC whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
  • SECOND-LINE OR GREATER MONOTHERAPY:KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
  • FIRST-LINE COMBINATION THERAPY:KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC)NSCLC. This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
  • RECURRENT OR METASTATIC HEAD AND NECK SQUAMOUS CELL CARCINOMA ON OR AFTER PLATINUM-CONTAINING CHEMOTHERAPY:KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
  • REFRACTORY OR RELAPSED cHL:KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
  • FIRST-LINE MONOTHERAPY—CISPLATIN INELIGIBLE:KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
  • SECOND-LINE MONOTHERAPY—POST–PLATINUM FAILURE:KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
  • ADVANCED MSI-H/dMMR CANCERS:KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)
    • solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
    • colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
    This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.
  • ADVANCED OR METASTATIC GASTRIC OR GEJ CANCER:KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
PD-L1 = programmed death ligand 1;
EGFR = epidermal growth factor receptor;
ALK = anaplastic lymphoma kinase;
HER2/neu = human epidermal growth factor receptor 2.
mNSCLC = metastatic NSCLC; 
PD-L1 = programmed death ligand 1;
EGFR = epidermal growth factor receptor;
ALK = anaplastic lymphoma kinase.
PD-L1 = programmed death ligand 1;
HER2/neu = human epidermal growth factor receptor 2.
SELECTED SAFETY INFORMATION for KEYTRUDA® (pembrolizumab)
  • KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.
  • KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.
  • KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.
  • KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.
  • KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. 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. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.
  • KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.
  • KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.
  • 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.
  • KEYTRUDA can cause other clinically important immune-mediated adverse reactions. These immune-mediated reactions may occur in any organ system. 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 KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.
  • The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. 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 postmarketing use of KEYTRUDA. Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment with KEYTRUDA vs the risk of possible organ rejection in these patients.
  • KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.
  • Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after being treated with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after treatment with KEYTRUDA on any trial, 6 patients (26%) developed graft-versus-host disease (GVHD), one of which was fatal, and 2 patients (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning, one of which was fatal. 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. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT. Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene promptly.
  • Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.
  • In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to 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%). Adverse reactions leading to interruption of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.
  • In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).
  • When KEYTRUDA was administered in combination with carboplatin and pemetrexed (carbo/pem) in advanced nonsquamous NSCLC, KEYTRUDA was discontinued in 10% of 59 patients. The most common adverse reaction resulting in discontinuation of KEYTRUDA (≥2%) was acute kidney injury (3.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 39% of patients; the most common (≥2%) were fatigue (8%), neutrophil count decreased (8%), anemia (5%), dyspnea (3.4%), and pneumonitis (3.4%). The most common adverse reactions (≥20%) with KEYTRUDA compared to carbo/pem alone were fatigue (71% vs 50%), nausea (68% vs 56%), constipation (51% vs 37%), rash (42% vs 21%), vomiting (39% vs 27%), dyspnea (39% vs 21%), diarrhea (37% vs 23%), decreased appetite (31% vs 23%), headache (31% vs 16%), cough (24% vs 18%), dizziness (24% vs 16%), insomnia (24% vs 15%), pruritus (24% vs 4.8%), peripheral edema (22% vs 18%), dysgeusia (20% vs 11%), alopecia (20% vs 3.2%), upper respiratory tract infection (20% vs 3.2%), and arthralgia (15% vs 24%). This study was not designed to demonstrate a statistically significant difference in adverse reaction rates for KEYTRUDA as compared to carbo/pem alone for any specified adverse reaction.
  • 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 (reported in at least 20% of patients) 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, with the exception of increased incidences of facial edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening hypothyroidism.
  • In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL, and treatment was interrupted due to adverse reactions in 26% of patients. Fifteen percent (15%) of patients had an adverse reaction requiring systemic corticosteroid therapy. Serious adverse reactions occurred in 16% of patients. The most frequent serious adverse reactions (≥1%) included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; one from GVHD after subsequent allogeneic HSCT and one from septic shock. The most common adverse reactions (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).
  • In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reactions (in ≥20% of patients) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%). Eighteen patients (5%) died from causes other than disease progression. Five patients (1.4%) who were treated with KEYTRUDA experienced sepsis which led to death, and 3 patients (0.8%) experienced pneumonia which led to death. Adverse reactions leading to interruption of KEYTRUDA occurred in 22% of patients; the most common (≥1%) were liver enzyme increase, diarrhea, urinary tract infection, acute kidney injury, fatigue, joint pain, and pneumonia. Serious adverse reactions occurred in 42% of patients, the most frequent (≥2%) of which were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis.
  • 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%). Adverse reactions leading to interruption of KEYTRUDA occurred in 20% of patients; the most common (≥1%) were urinary tract infection (1.5%), diarrhea (1.5%), and colitis (1.1%). The most common adverse reactions (≥20%) in patients who received KEYTRUDA vs those who received chemotherapy were fatigue (38% vs 56%), musculoskeletal pain (32% vs 27%), pruritus (23% vs 6%), decreased appetite (21% vs 21%), nausea (21% vs 29%), and rash (20% vs 13%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients, the most frequent (≥2%) of which were urinary tract infection, pneumonia, anemia, and pneumonitis.
  • It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.
  • 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 every 3 weeks. Patients received KEYTRUDA for a median of 3 doses (range 1–17 doses), with 34 patients (85%) receiving KEYTRUDA 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%).
HNSCC = head and neck squamous cell carcinoma; cHL = classical Hodgkin lymphoma; PD-1 = programmed death receptor-1; NSCLC = non–small cell lung cancer; PD-L1 = programmed death ligand 1. Before prescribing KEYTRUDA, please read the accompanying Prescribing Information. The Medication Guide also is available.

References:
  1. Data available on request from Merck, Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package ONCO-1208197-0005.
  2. Opdivo [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2017.
  3. Robert C, Schachter J, Long GV, et al, for the KEYNOTE-006 investigators. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–2532.
  4. U.S. National Institutes of Health. Study to Evaluate the Safety and Efficacy of Two Different Dosing Schedules of Pembrolizumab (MK-3475) Compared to Ipilimumab in Participants With Advanced Melanoma (MK-3475-006/KEYNOTE-006). https://clinicaltrials.gov/ct2/show/NCT01866319. Accessed March 23, 2017.
  5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Melanoma V.1.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed March 1, 2017. To view the most recent and complete version of the guidelines, go online to NCCN.org.


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