• For Oncologists
  • For Pathologists
 
Biomarker Testing
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INFORMATION ON PD-L1 EXPRESSION AND TESTING
FOR ONCOLOGISTS

TEST
Test All Patients at Diagnosis of Squamous and Nonsquamous NSCLC
Test all patients for PD-L1 expression at diagnosis of squamous and nonsquamous non–small cell lung cancer (NSCLC)
EVALUATE
To Select Appropriate Treatment for NSCLC, Evaluate PD-L1 Expression
Evaluate PD-L1 expression to select appropriate treatment
TREAT
Treat Appropriate Patients With KEYTRUDA® (pembrolizumab) for NSCLC
Treat appropriate patients with KEYTRUDA
NCCN Guidelines® Recommend PD-L1 Testing During Diagnostic Evaluation of Patients for mNSCLC Treatment
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend PD-L1 testing as a part of the diagnostic evaluation of patients for treatment of mNSCLC.1

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.


START INFORMED: TEST ALL PATIENTS FOR PD-L1 EXPRESSION AT DIAGNOSIS OF SQUAMOUS AND NONSQUAMOUS mNSCLC

  • PD-L1 is an immune-related biomarker that can be expressed on tumor cells.
  • Evaluating PD-L1 expression level at diagnosis of NSCLC contributes to a better understanding of your patient’s tumor and helps inform treatment decisions.
  • For patients not tested at diagnosis, recently obtained or archival formalin-fixed, paraffin-embedded tissue samples may be tested for PD-L1.2,3

PD-L1 EXPRESSION LEVEL AND/OR HISTOLOGY HELP INFORM TREATMENT DECISIONS WITH KEYTRUDA

KEYTRUDA + carboplatin/pemetrexed: First-line treatment for all appropriate nonsquamous patients with mNSCLC

Appropriate patients include:

  • Any level of PD-L1 expression
  • PD-L1 negative
  • PD-L1 result unavailable or pending
  • Untested for PD-L1 expression

Most patients diagnosed with mNSCLC have nonsquamous histology

PD-L1 Expression and/or Histology Help Inform Treatment Decisions
About 70% to 75% of all patients with NSCLC have nonsquamous histology.4

KEYTRUDA as monotherapy: First-line treatment for mNSCLC

  • Nonsquamous or squamous NSCLC
  • No EGFR or ALK genomic tumor aberrations
  • High PD-L1 expression: TPS ≥50%
ALTALT

KEYTRUDA as monotherapy: Second-line or greater treatment for mNSCLC

  • Nonsquamous or squamous NSCLC
  • Previously treated with platinum-containing chemotherapy and EGFR or ALK therapy, if appropriate
  • PD-L1 expression: TPS ≥1%
ALTALT
Request PD-L1 Testing for All Patients at Diagnosis of Squamous and Nonsquamous NSCLC
Request PD-L1 testing for all patients at diagnosis of squamous and nonsquamous NSCLC to help identify patients most likely to benefit from treatment with KEYTRUDA.

PREVALENCE OF PD-L1 EXPRESSION BASED ON PATIENTS WITH mNSCLC SCREENED FOR PD-L1 IN CLINICAL TRIALS FOR KEYTRUDA

HIGH PD-L1 EXPRESSION (TPS ≥50%) in KEYNOTE-024 study5
PD-L1≥50%

30% (n=500/1,653) of patients with mNSCLC had high PD-L1 expression.

PD-L1 EXPRESSION (TPS ≥1%) in KEYNOTE-010 study2
PD-L1≥1%

66% (n=1,475/2,222) of patients with mNSCLC had PD-L1 expression.


  • The prevalence of PD-L1 expression may be higher than that of other biomarkers tested in NSCLC, such as EGFR (~20%)6,7,a or ALK (~2% to 7%).7,8

aFrequency of EGFR mutations in NSCLC of adenocarcinoma histology.6

PD-L1 = programmed death ligand 1; EGFR = epidermal growth factor receptor; ALK = anaplastic lymphoma kinase; TPS = tumor proportion score.


PD-L1 TESTING IS AVAILABLE AT NATIONAL REFERENCE LABORATORIES

  • Order PD-L1 testing from your pathology laboratory as you would do for any other biomarker test.
  • Your pathologist may be able to test for PD-L1 in your hospital or facility laboratory or may request testing from a reference laboratory where PD-L1 testing is offered.
    • The reference laboratories below offer the PD-L1 IHC 22C3 pharmDx, the first FDA-approved companion diagnostic test for PD-L1 testing in NSCLC.9

PD-L1 expression testing is available at these national reference laboratories

  • The above national reference laboratories do not represent an exclusive network of accredited pathology laboratories offering PD-L1 testing. PD-L1 testing may be offered by accredited pathology laboratories other than the national reference laboratories identified above.
  • Regional reference laboratories that offer accredited PD-L1 testing include:
  • Merck does not endorse the use of any particular laboratory over another or guarantee the work performed by any laboratory.
  • The processing time for PD-L1 testing is consistent with that of other biomarkers analyzed using IHC.10

IHC = immunohistochemistry.

Contact Your Pathologist or a Merck Representative With Questions About PD-L1 Testing
Contact your pathologist or a Merck representative with questions about PD-L1 testing.

WATCH A VIDEO ON THE ROLE OF BIOMARKERS IN NSCLC

INFORMATION ON PD-L1 EXPRESSION AND TESTING
FOR PATHOLOGISTS

TEST
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Test all patients for PD-L1 expression at diagnosis of squamous and nonsquamous non–small cell lung cancer (NSCLC)
IDENTIFY
image
Identify tumor proportion score (TPS) and PD-L1 expression level in NSCLC1
INFORM
image
Inform treatment decisions with a report that includes TPS and expression level

Test for PD-L1 expression at diagnosis of squamous and nonsquamous mNSCLC to help inform treatment decisions across all lines of therapy

  • PD-L1 expression helps to identify patients most likely to benefit from treatment with KEYTRUDA.
  • Recently obtained or archival formalin-fixed, paraffin-embedded tissue samples may be tested for PD-L1 expression.2,3

mNSCLC = metastatic NSCLC; PD-L1 = programmed death ligand 1.

NCCN Guidelines® Recommend PD-L1 Testing During Diagnostic Evaluation of Patients for mNSCLC Treatment
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend PD-L1 testing as a part of the diagnostic evaluation of patients for treatment of mNSCLC.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.


IDENTIFY TPS AND PD-L1 EXPRESSION LEVEL IN NSCLC

  • Evaluate the percentage of tumor cells with PD-L1 staining to assess the patient’s TPS between 0% and 100%.1
  • TPS is the percentage of viable tumor cells showing partial or complete membrane staining relative to all viable tumor cells present in the sample (positive and negative).5

PD-L1 expression level of the specimen can be interpreted as1,5:

No PD-L1 Expression: TPS <1%No PD-L1 Expression: TPS <1%

INFORM TREATMENT DECISIONS WITH A REPORT FOR
PD-L1 EXPRESSION

  • The reporting elements in this sample report provide important information to help oncologists make treatment decisions for patients with mNSCLC.5
  • Note: Report TPS ≥50% as high PD-L1 expression.1
Sample Diagnostic Lab Report With PD-L1 IHC AnalysisSample Diagnostic Lab Report With PD-L1 IHC Analysis
Include the TPS and an Assessment of PD-L1 Expression Level in Your Pathology Report
Be sure to include both the TPS and an assessment of PD-L1 expression level in your pathology report to best inform the oncologist’s treatment decisions.

WHERE TO TEST

  • PD-L1 testing can be conducted within your hospital or facility, or you may order testing from a reference laboratory.
    • The reference laboratories below offer the PD-L1 IHC 22C3 pharmDx, the first FDA-approved companion diagnostic test for PD-L1 testing in NSCLC.6

PD-L1 expression testing is available at these national reference laboratories

  • The above national reference laboratories do not represent an exclusive network of accredited pathology laboratories offering PD-L1 testing. PD-L1 testing may be offered by accredited pathology laboratories other than the national reference laboratories identified above.
  • Regional reference laboratories that offer accredited PD-L1 testing include:
  • Merck does not endorse the use of any particular laboratory over another or guarantee the work performed by any laboratory.

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.

  • 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-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. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.8.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed July 19, 2017. To view the most recent and complete version of the guidelines, go online to NCCN.org.
  2. Herbst RS, Baas P, Kim D-W, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–1550.
  3. Supplementary Appendix to: Herbst RS, Baas P, Kim D-W, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 2015; published online Dec 19. http://dx.doi.org/10.1016/S0140-6736(15)01281-7. Accessed April 6, 2017.
  4. American Cancer Society. What is non-small cell lung cancer? https://www.cancer.org/cancer/non-small-cell-lungcancer/about/what-is-non-small-cell-lung-cancer.html. Updated May 16, 2016. Accessed August 8, 2017.
  5. Reck M, Rodríguez-Abreu D, Robinson AG, et al, for the KEYNOTE-024 investigators. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N Engl J Med. 2016;375(19):1823–1833.
  6. Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res. 2015;5(9):2892–2911.
  7. Gainor JF, Varghese AM, Ou SHI, et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non–small cell lung cancer. Clin Cancer Res. 2013;19(15):4273–4281.
  8. Kwak EL, Bang Y-J, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non–small-cell lung cancer. N Engl J Med. 2010;363(18):1693–1703.
  9. FDA approves Keytruda for advanced non-small cell lung cancer [news release]. Silver Spring, MD: U.S. Food and Drug Administration; October 2, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm465444.htm. Accessed July 8, 2016.
  10. NeoGenomics Laboratories. Test Menu: favorites. http://neogenomics.com/Test-Menu/immunohistochemistryihc. Accessed August 8, 2016.
References:
  1. Dako Denmark A/S. Instructions for Use: PD-L1 IHC 22C3 pharmDx.
  2. Herbst RS, Baas P, Kim D-W, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–1550.
  3. Supplementary Appendix to: Herbst RS, Baas P, Kim D-W, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 2015; published online Dec 19. http://dx.doi.org/10.1016/S0140-6736(15)01281-7. Accessed April 6, 2017.
  4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.8.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed July 19, 2017. To view the most recent and complete version of the guidelines, go online to NCCN.org.
  5. Dako Denmark A/S. PD-L1 IHC 22C3 pharmDx Interpretation Manual.
  6. FDA approves Keytruda for advanced non-small cell lung cancer [news release]. Silver Spring, MD: U.S. Food and Drug Administration; October 2, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm465444.htm. Accessed July 8, 2016.


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