• For Oncologists
  • For Pathologists
 
Biomarker Testing
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ORDERING MSI OR MMR TESTING ACROSS ADVANCED CANCERS MAY HELP TO IDENTIFY PATIENTS FOR TREATMENT WITH KEYTRUDA

TEST
Ordering MSI or MMR Testing Across Advanced Cancers
Request MSI or MMR testing in your patients with advanced cancers.
TREAT
Identify Patients for Treatment With KEYTRUDA® (pembrolizumab) Through MSI or MMR Testing
If MSI-H/dMMR, treat your appropriate patients with KEYTRUDA.

MSI = microsatellite instability; MMR = mismatch repair; MSI-H = microsatellite instability-high; dMMR = mismatch repair deficient.


MSI-H/dMMR Occurs in Different Tumor Types

Microsatellite Instability-High/Mismatch Repair Deficient Can Occur in Gastrointestinal Cancers

Gastrointestinal cancersBiliary, colorectal, esophageal, gastric or GEJ, pancreatic, small intestinal

Microsatellite Instability-High/Mismatch Repair Deficient Can Occur in Women's Cancers

Women’s cancersBreast, endometrial

Microsatellite Instability-High/Mismatch Repair Deficient Can Occur in Genitourinary Cancers

Genitourinary cancersBladder, prostate, renal cell

Microsatellite Instability-High/Mismatch Repair Deficient Can Occur in Different Tumor Types

Other cancersRetroperitoneal adenocarcinoma, sarcoma, small cell lung, thyroid

Microsatellite Instability-High/Mismatch Repair Deficient Can Be Sporadic or Hereditary
MSI-H/dMMR can be sporadic or hereditary. Of the estimated 15% of patients with colorectal cancer who have MSI-H, about 83% have sporadic disease and only about 17% have Lynch syndrome.1

GEJ = gastroesophageal junction.


REQUEST MSI OR MMR TESTING IN YOUR PATIENTS WITH ADVANCED CANCERS

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer, Rectal Cancer, and for Uterine Neoplasms recommend2–4:

  • Universal MMR or MSI testing for all patients with a personal history of colon or rectal cancer to identify individuals with Lynch syndrome, to inform use of immunotherapy in patients with metastatic disease, and to inform decisions for patients with stage II disease.2,3
  • Universal testing of endometrial carcinomas for MMR gene.4
  • Your pathologist may be able to perform MSI or MMR testing in your hospital or facility laboratory or may request testing from a reference laboratory where MSI or MMR testing is offered.

National Comprehensive Cancer Network® (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.

Requesting MSI or MMR Testing Across Advanced Cancers
Requesting MSI or MMR testing across advanced cancers
may help to identify patients for treatment with KEYTRUDA.

PCR for MSI or IHC for MMR can be requested to identify patients appropriate for treatment with KEYTRUDA

  • PCR for MSI and IHC for MMR are different assays measuring the same biological effect.2
  • In clinical trials for KEYTRUDA, patients were identified using local PCR or IHC, regardless of histology.

MSI or MMR Status Should Be Reported Clearly Across Advanced Cancers to Identify Patients Appropriate for Treatment With KEYTRUDA

MSI or MMR Status Should Be Reported Clearly Across Advanced CancersMSI or MMR Status Should Be Reported Clearly Across Advanced Cancers

PCR = polymerase chain reaction; IHC = immunohistochemistry; MSS = microsatellite stable; MSI-L = microsatellite instability-low.

  • IHC test results can use various terms to describe patients eligible for KEYTRUDA, including:
    • Loss of nuclear expression5
    • Negative7,8
    • Absent9,10
    • Aberrant10
    • Abnormal5
    • Loss of expression5
Treating Appropriate Patients With KEYTRUDA® (pembrolizumab) for MSI-H/dMMR
If MSI-H/dMMR, treat your appropriate patients with KEYTRUDA.

PERFORMING MSI OR MMR TESTING ACROSS ADVANCED CANCERS MAY HELP TO IDENTIFY PATIENTS ELIGIBLE FOR TREATMENT WITH KEYTRUDA

TEST
Ordering MSI or MMR Testing Across Advanced Cancers

Perform MSI or MMR testing in patients with advanced cancers.

PCR for MSI or IHC for MMR can be used to identify appropriate patients for therapy with KEYTRUDA.

INFORM
image

Include MSI or MMR test results in reports for advanced cancers.

Clearly designate “MSI-H” or “dMMR” on the report for any tissue samples that have abnormal MSI PCR or MMR IHC results.

dMMR = mismatch repair deficient; IHC = immunohistochemistry; MMR = mismatch repair; MSI = microsatellite instability; MSI-H = microsatellite instability-high; PCR = polymerase chain reaction.


MSI-H/dMMR Occurs in Different Tumor Types

Microsatellite Instability-High/Mismatch Repair Deficient Can Occur in Gastrointestinal Cancers

Gastrointestinal cancersBiliary, colorectal, esophageal, gastric or GEJ, pancreatic, small intestinal

Microsatellite Instability-High/Mismatch Repair Deficient Can Occur in Women's Cancers

Women’s cancersBreast, endometrial

Microsatellite Instability-High/Mismatch Repair Deficient Can Occur in Genitourinary Cancers

Genitourinary cancersBladder, prostate, renal cell

Microsatellite Instability-High/Mismatch Repair Deficient Can Occur in Different Tumor Types

Other cancersRetroperitoneal adenocarcinoma, sarcoma, small cell lung, thyroid

Microsatellite Instability-High/Mismatch Repair Deficient Can Be Sporadic or Hereditary
MSI-H/dMMR can be sporadic or hereditary. Of the estimated 15% of patients with colorectal cancer who have MSI-H, about 83% have sporadic disease and only about 17% have Lynch syndrome.1

GEJ = gastroesophageal junction.


NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer, Rectal Cancer, and for Uterine Neoplasms recommend2–4:

  • Universal MMR or MSI testing for all patients with a personal history of colon or rectal cancer to identify individuals with Lynch syndrome, to inform use of immunotherapy in patients with metastatic disease, and to inform decisions for patients with stage II disease.2,3
  • Universal testing of endometrial carcinomas for MMR gene.4

National Comprehensive Cancer Network® (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.


PCR for MSI or IHC for MMR can be performed to identify appropriate patients for KEYTRUDA

  • PCR for MSI and IHC for MMR are different assays measuring the same biological effect.2
  • In clinical trials for KEYTRUDA, patients were identified using local PCR or IHC, regardless of histology.
  • MSI or MMR testing can be conducted within your hospital or facility, or you may order testing from a reference laboratory.
  • As of yet, there is no FDA-approved MSI or MMR test. Consequently, MSI and MMR testing is considered laboratory developed, and the lab must conduct the appropriate analytic validation testing.5

MSI or MMR Status Should Be Reported Clearly Across Advanced Cancers to Identify Patients Appropriate for Treatment With KEYTRUDA

ALTALT

MSS = microsatellite stable; MSI-L = microsatellite instability-low.


EXAMPLES OF MMR AND MSI TEST RESULTS

IHC detects the presence or absence of MMR protein expression8,9

PCR compares the length of nucleotide repeats in tumor cells and normal cells10

MSI Results

  • MSI-H is detected by comparison of tumor tissue with normal tissue, showing differences in peak patterns.
    The arrows represent shifts in base pairs compared with normal tissue.
Help Identify Patients With Advanced Cancers Eligible for Treatment With KEYTRUDA® (pembrolizumab)
Help identify patients with advanced cancers who are eligible for treatment with KEYTRUDA.

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 (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.
  • REFRACTORY OR RELAPSED PMBCL:KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 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 confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
  • FIRST-LINE MONOTHERAPY—CISPLATIN INELIGIBLE:KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) 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 (mUC) 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.
  • ADVANCED CERVICAL CANCER:KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. 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.
  • Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA. While immune-mediated adverse reactions usually occur during treatment with PD-1/PD-L1 blocking antibodies, they may occur after discontinuation of treatment. 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, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma (cHL), 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 treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 developed graft-versus-host disease (GVHD) (one fatal case) and 2 developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (one 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.
  • 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%).
  • In KEYNOTE-021(G1), 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-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL, and treatment was interrupted due to adverse reactions in 15%. Twenty-five percent (25%) 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. The most common adverse reactions (occurring in ≥20% of patients) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).
  • 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.
  • In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients (in Cohort E) with recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA. The most frequent serious adverse reactions reported included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (occurring in ≥20% of patients) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).
  • 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 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; PD-1 = programmed death receptor-1; PD-L1 = programmed death ligand 1; NSCLC = non–small cell lung cancer. Before prescribing KEYTRUDA, please read the accompanying Prescribing Information. The Medication Guide also is available.

References:
  1. Dudley JC, Lin M-T, Le DT, et al. Microsatellite instability as a biomarker for PD-1 blockade. Clin Cancer Res. 2016;22(4):813–820.
  2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.2.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed March 15, 2017. To view the most recent and complete version of the guidelines, go online to NCCN.org.
  3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer V.3.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed July 31, 2017. To view the most recent and complete version of the guidelines, go online to NCCN.org.
  4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Uterine Neoplasms V.3.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed July 26, 2017. To view the most recent and complete version of the guidelines, go online to NCCN.org.
  5. Bartley AN, Hamilton SR, Alsabeh R, et al. Template for reporting results of biomarker testing of specimens from patients with carcinoma of the colon and rectum. Arch Pathol Lab Med. 2014;138(2):166–170.
  6. Vilar E, Gruber SB. Microsatellite instability in colorectal cancer—the stable evidence. Nat Rev Clin Oncol. 2010;7(3):153–162.
  7. Chen W, Swanson BJ, Frankel WL. Molecular genetics of microsatellite-unstable colorectal cancer for pathologists. Diagn Pathol. 2017;12:24. doi:10.1186/s13000-017-0613-8.
  8. Long Q, Peng Y, Tang Z, et al. Role of endometrial cancer abnormal MMR protein in screening Lynch-syndrome families. Int J Clin Exp Pathol. 2014;7(10):7297–7303.
  9. College of American Pathologists. POET report: perspectives on emerging technology. Prognostic uses of MSI testing. Northfield, IL. 2011.
  10. McConechy MK, Talhouk A, Li-Chang HH, et al. Detection of DNA mismatch repair (MMR) deficiencies by immunohistochemistry can effectively diagnose the microsatellite instability (MSI) phenotype in endometrial carcinomas. Gynecol Oncol. 2015;137(2):306–310.
References:
  1. Dudley JC, Lin M-T, Le DT, et al. Microsatellite instability as a biomarker for PD-1 blockade. Clin Cancer Res. 2016;22(4):813–820.
  2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.2.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed March 15, 2017. To view the most recent and complete version of the guidelines, go online to NCCN.org.
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