Pembrolizumab (Keytruda) may be considered medically necessary for ANY of the following conditions:
Anal Carcinoma, Squamous Cell Carcinoma (NCCN)
- Treatment of individuals with squamous cell anal carcinoma as second- line or subsequent, single agent therapy for metastatic disease; or
Bladder (Urothelial) Carcinoma (FDA)
- Treatment of individuals with locally advance or metastatic Urothelial Carcinoma who:
- Are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (combined Positive Score (CPS) greater than or equal to ten (10) as determined by an FDA-approved test; or
- Are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status; or
- Have disease progression during or following platinum-containing chemotherapy; or
- Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy; or
- Treatment of individuals with Bacillus Calmette-Guerin (BCG) unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy; or
Bladder (Urothelial) Carcinoma (NCCN)
- As first-line systemic therapy as a single agent in cisplatin ineligible individuals whose tumors express PD-L1 or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression for:
- Stage II (cT2, N0) disease if tumor is present following reassessment of tumor status two – three (2-3) months after primary treatment with concurrent chemoradiotherapy; or
- Stage IIIA (cT3, N0; cT4a, N0; cT1-T4a, N1) disease if tumor is present following reassessment of tumor status two – three (2-3) months after primary treatment with concurrent chemoradiotherapy; or
- Non-cystectomy candidates with stage IIIA (cT3, N0; cT1-4a, N1) disease if tumor is present upon reassessment of tumor status two-three (2-3) months after primary treatment; or
- Stage IIIB (cT1-T4a, N2,3) disease as downstaging systemic therapy; or
- Stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with concurrent chemoradiotherapy; or
- Stage IVA (cT4b, any N, M0; any T, any N, M1a) disease; or
- Stage IVB (any T, any N, M1b) disease; or
- Muscle invasive local recurrence or persistent disease in a preserved bladder; or
- Metastatic or local recurrence post cystectomy; or
- As second-line systemic therapy post-platinum as a single agent for:
- Stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with downstaging systemic therapy or concurrent chemoradiotherapy; or
- Stage IVA (cT4b, any N, M0) disease if tumor is present following reassessment of tumor status after primary treatment with first-line systemic therapy or concurrent chemoradiotherapy; or
- Stage IVA (any T, any N, M1a) disease if stable disease or progression following reassessment of tumor status after primary treatment with first-line systemic therapy; or
- Stage IVB (any T, any N, M1b) disease; or
- Muscle invasive local recurrence or persistent disease in a preserved bladder; or
- Metastatic or local recurrence post cystectomy; or
- Treatment of select individuals with BCG-unresponsive, high-risk, non-muscle invasive bladder cancer with Tis with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy; or
Bladder (Urothelial) Cancer, Urethra, Primary (NCCN)
- Used as a single agent for recurrent or metastatic disease as:
- First-line systemic therapy in cisplatin ineligible individuals whose tumors express PD-L1 or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression; or
- Second-line systemic therapy post-platinum; or
- Subsequent-line systemic therapy; or
- Therapy for metastatic disease as a single agent for:
- First-line systemic therapy in cisplatin ineligible individuals whose tumors express PD-L1 or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression; or
- Second-line systemic therapy post-platinum; or
- Subsequent-line systemic therapy; or
- Primary treatment as a single agent for clinical stage T3-4, cN1-2 disease or cN1-2 palpable inguinal lymph nodes as first-line systemic therapy in cisplatin ineligible individuals whose tumors express PD-L1 or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression; or
Bone Cancer – Chondrosarcoma (NCCN)
- Single-agent therapy for individuals with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options; or
Bone Cancer – Ewing Sarcoma, Mesenchymal Chondrosarcoma (NCCN)
- Single-agent therapy for individuals with unresectable or metastatic, MSI-H or dMMR tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options; or
Bone Cancer – Osteosarcoma (NCCN)
- Single-agent therapy for individuals with unresectable or metastatic, MSI-H or dMMR tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options; or
Breast Cancer – Invasive Breast Cancer (NCCN)
- Single agent therapy for recurrent or stage IV (M1) disease that is unresectable or metastatic and MSI-H or dMMR that has progressed following prior treatment and has no satisfactory alternative treatment options; or
Central Nervous System Cancers - Extensive Brain Metastases (NCCN)
- Single-agent treatment for extensive brain metastases in individuals with melanoma or PD-L1-positive non-small cell lung cancer (NSCLC); or
- Primary treatment in individuals with small asymptomatic brain metastases; or
- Treatment for recurrent disease with stable systemic disease or reasonable systemic treatment options; or
Central Nervous System Cancers - Limited Brain Metastases (NCCN)
- Single-agent treatment for limited brain metastases in individuals with melanoma or PD-L1-positive non-small cell lung cancer, NSCLC:
- Initial treatment of individuals with small asymptomatic brain metastases; or
- For recurrent brain metastases; or
- Treatment for relapsed disease with either stable systemic disease or reasonable systemic treatment options; or
Cervical Cancer (FDA)
- Treatment of individuals with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 [Combined Positive Score (CPS) greater than or equal to one (1)]; or
Cervical Cancer – Squamous cell carcinoma, Adenocarcinoma (NCCN)
- Preferred second-line therapy as a single agent for recurrent or metastatic disease if:
- Instability-high, MSI-H, or mismatch repair deficient, dMMR tumors; or
- Disease progression on or after chemotherapy in individuals whose tumors express PDL1 (CPS ≥1); or
- Treatment of individuals with unresectable or metastatic tumor mutational burden-high (TMB-H) (greater than or equal to 10 mut/Mb) that have progressed following prior treatment and who have no satisfactory alternative treatment options; or
Colon Adenocarcinoma (NCCN)
- As single agent in individuals with dMMR/MSI-H only as:
- Adjuvant treatment following resection and/or local therapy for resectable metachronous metastases in individuals who have received previous chemotherapy for colon adenocarcinoma; or
- Adjuvant treatment for unresectable metachronous metastases that converted to resectable disease after primary treatment. Biologic therapy is only appropriate for continuation of favorable response from conversion therapy for colon adenocarcinoma; or
- Subsequent therapy as a single agent (if nivolumab or pembrolizumab not previously given) for advanced or metastatic disease dMMR/MSI-H only, if no previous treatment with a checkpoint inhibitor, following previous oxaliplatin- irinotecan- and/or fluoropyrimidine-based therapy; or
- Primary treatment as a single agent for unresectable metachronous metastases dMMR/MSI-H only and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months; or
- Therapy as a single agent in individuals dMMR/MSI-H only:
- As primary treatment for locally unresectable or medically inoperable disease; or
- For unresectable synchronous liver and/or lung metastases that remain unresectable after primary systemic therapy; or
- As primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for patients with existing or imminent obstruction; or
- For synchronous unresectable metastases of other sites; or
- As primary treatment for unresectable metachronous metastases in individuals who have not received previous adjuvant FOLFOX or CapeOX within the past 12 months, who have received previous fluorouracil/leucovorin (5-FU/LV) or capecitabine therapy, or who have not received any previous chemotherapy; or
- For unresectable metachronous metastases that remain unresectable after primary treatment; or
Cutaneous Squamous Cell Carcinoma (cSCC) (FDA)
- Treatment of individuals with recurrent or metastatic cSCC that is not curable by surgery or radiation; or
Endometrial Carcinoma (FDA)
- Treatment of individuals with advanced endometrial carcinoma that in not MSI-H or dMMR; and
- Individual has disease progression following prior systemic therapy; and
- Individual is not a candidate for curative surgery or radiation; and
- Pembrolizumab (Keytruda) is given in combination with lenvatinib; or
Esophageal Cancer (FDA)
- Treatment of individuals with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 [Combined Positive Score (CPS) greater than or equal to 10]; and
- Disease progression after one (1) or more prior lines of systemic therapy; or
Esophageal and Esophagogastric Junction Cancers – Squamous Cell Carcinoma, Adenocarcinoma and Gastric Cancer - Adenocarcinoma (NCCN)
- Treatment of individuals as palliative therapy in non-surgical candidates or unresectable locally advance, recurrent, or metastatic disease and Karnofsky performance score greater than or equal to 60% or Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to two (2) and if no previous treatment with a checkpoint inhibitor as:
- Second-line or subsequent therapy as a single agent for microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors; or
- Second-line therapy for esophageal squamous cell carcinoma (SCC) with PD-L1 expression by CPS of levels greater than or equal to 10; or
- Third-line or subsequent therapy as a single agent for esophageal and EGJ adenocarcinoma with PD-L1 expression levels by CPS of greater than or equal to one (1); or
Gastric Cancer (FDA)
- Treatment of individuals with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma:
- Whose tumors express PD-L1 [Combined Positive Score (CPS) greater than or equal to 1]; and
- With disease progression on or after two (2) or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy; or
Gastric Cancer, Adenocarcinoma (NCCN)
- Palliative therapy for locoregional disease in individuals who are not surgical candidates or have recurrent, or metastatic disease and Karnofsky performance score greater than or equal to 60% or ECOG performance score less than or equal to 2 as:
- Second-line or subsequent therapy as a single agent for microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors; or
- Third-line or subsequent therapy as a single agent for gastric adenocarcinoma with PD-L1 expression levels by CPS of greater than or equal to 1; or
Genitourinary, Upper Tract Tumors or Urothelial Carcinoma of the Prostate (Bladder) (NCCN)
- Used as a single agent for metastatic disease as:
- First-line systemic therapy in cisplatin ineligible individuals whose tumors express PD-L1 or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression; or
- Second-line systemic therapy post-platinum; or
- Subsequent systemic therapy post-platinum; or
Gestational Trophoblastic Neoplasia (NCCN)
- Single agent therapy for multiagent chemotherapy resistant:
- High risk disease; or
- Recurrent or progressive intermediate trophoblastic tumor (placental site trophoblastic tumor or epithelioid trophoblastic tumor) following treatment with a platinum/etoposide-containing regimen; or
Head and Neck Squamous Cell Cancer, HNSCC (FDA)
- Combination treatment with platinum and FU for first-line treatment of individuals with metastatic or unresectable, recurrent HNSCC; or
- Single agent treatment for first line treatment of individuals with metastatic or unresectable, recurrent HNSCC whose tumors express PD-L1 (Combined Positive Score (CPS) greater than or equal to 1); or
- Single agent treatment of individuals with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy; or
Head and Neck Cancer, Very Advanced, Squamous Cell Carcinoma with Mixed Subtypes (NCCN)
- Therapy as single agent first-line therapy option for non-nasopharyngeal cancer tumors that express PD-L1 with CPS greater than or equal to one (1) in individuals with:
- PS 2 for newly diagnosed T4b, any N 0-3, M0 disease, unresectable nodal disease with no metastases, non-metastatic disease for individuals who are unfit for surgery or unresectable locoregional recurrence without prior radiation therapy (RT); or
- PS 0-2 for metastatic (M1) disease at initial presentation, recurrent/persistent disease with distant metastases, unresectable locoregional recurrence with prior RT or unresectable second primary with prior RT; or
- Unresectable locoregional recurrence without prior RT and PS 3; or
- Therapy as a single agent subsequent therapy option, if immunotherapy not previously used for non-nasopharyngeal cancer if disease progression on or after platinum-containing chemotherapy in individuals with:
- PS 0-1 and persistent or progressive metastatic disease (M1) at initial presentation after first-line therapy; or
- PS 0-2 and recurrent/persistent disease with distant metastases; or
- PS 0-2 and unresectable locoregional recurrence or second primary with prior RT; or
- PS 3 and unresectable locoregional recurrence without prior RT; or
- Systemic therapy as a first-line or subsequent therapy option for non-nasopharyngeal cancer and PS 0-1 for metastatic (M1) disease at initial presentation, recurrent/persistent disease with distant metastases, unresectable locoregional recurrent with prior RT, or unresectable second primary with prior RT in combination with fluorouracil and either carboplatin or cisplatin; or
- Used as combination systemic therapy in non-nasopharyngeal cancer for resectable locoregional recurrence without prior RT given with fluorouracil and either carboplatin or cisplatin; or
- Systemic therapy as a single agent subsequent-line option for nasopharyngeal cancer if previously treated, PD-L1-positive recurrent or metastatic disease in individuals with PS 0-2 for:
- Recurrent/persistent disease with distant metastases; or
- Unresectable locoregional recurrence or second primary with prior RT; or
Hepatobiliary Cancer, HCC (FDA)
- Treatment of individuals with HCC who have been previously treated with sorafenib; or
Hepatocellular Carcinoma, Adenocarcinoma (NCCN)
- Primary treatment as a single agent for unresectable or metastatic biliary tract cancers: gallbladder cancer (adenocarcinoma) that is MSI-H and/or dMMR; or
- Primary treatment as a single agent for unresectable or metastatic biliary tract cancers: extrahepatic cholangiocarcinoma (adenocarcinoma) that is MSI-H) and/or dMMR; or
- Subsequent treatment as a single agent for progression on or after systemic treatment for unresectable or metastatic biliary tract cancers: extrahepatic cholangiocarcinoma (adenocarcinoma) that is MSI-H and/or dMMR; or
- Primary treatment as a single agent for unresectable or metastatic biliary tract cancers: intrahepatic cholangiocarcinoma (adenocarcinoma) that is MSI-H and/or dMMR; or
- Subsequent treatment as a single agent for progression on or after systemic treatment for unresectable or metastatic biliary tract cancers: Intrahepatic Cholangiocarcinoma (adenocarcinoma) that is MSI-H and/or dMMR; or
- Subsequent treatment as a single agent for progression on or after systemic treatment for unresectable or metastatic biliary tract cancers: gallbladder cancer (adenocarcinoma) that is MSI-H and/or dMMR; or
- Subsequent treatment as a single agent for progressive disease in individuals (Child-Pugh Class A only) who have not been previously treated with a checkpoint inhibitor and:
- Have unresectable disease and are not a transplant candidate; or
- Are inoperable by performance status or comorbidity, or have local disease or local disease with minimal extrahepatic disease only; or
- Have metastatic disease or extensive liver tumor burden; or
Kidney (Renal) Cell Carcinoma, RCC (FDA)
- Combination therapy with axitinib, for first line treatment of individuals with advanced RCC; or
Kidney Cancer, Clear Cell (NCCN)
- Used in combination with axitinib for relapsed or stage IV disease;
- As preferred first-line therapy for clear cell histology and favorable risk; or
- As preferred first-line therapy for clear cell histology and poor/intermediate risk; or
- As subsequent therapy for clear cell histology; or
Leukemia, Chronic Lymphocytic /Small Lymphocytic Lymphoma (NCCN)
- As a single agent; or
- in combination with ibrutinib for:
- Treatment of histologic (Richter's) transformation to diffuse large B-cell lymphoma (clonally related or unknown clonal status); and
- For individuals with del(17p)/TP53 mutation; or
- Individuals who are chemotherapy refractory and unable to receive chemoimmunotherapy; or
Lung Cancer, NSCLC (FDA)
- As first-line treatment in combination with pemetrexed and platinum chemotherapy for metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations; or
- As first-line treatment in combination with carboplatin and either paclitaxel or nab-paclitaxel (paclitaxel protein-bound) for metastatic squamous NSCLC; or
- As first-line, single agent for NSCLC expressing PD-L1 (Tumor Proportion Score (TPS) greater than or equal to 1%), with no EGFR or ALK genomic tumor aberrations, and is:
- Stage III in individuals who are not candidates for surgical resection or definitive chemoradiation; or
- Metastatic; or
- As a single agent for metastatic NSCLC for tumors with express PD-L1 (TPS greater than or equal to 1%) with disease progression on or after platinum-containing chemotherapy. Individuals with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab (Keytruda); or
Lung Cancer, NSCLC, Adenocarcinoma (with mixed subtypes), Large Cell Carcinoma, Squamous Cell Carcinoma (NCCN)
- Treatment for recurrent, advanced or metastatic disease as first-line therapy for PD-L1 expression-positive (≥1%) tumors that are EGFR, ALK, ROS1, BRAF, MET exon 14 skipping mutation, and RET negative*** and no contraindications to the addition of pembrolizumab (Keytruda) or atezolizumab (Tecentriq) and performance status 0-2:
- As a single agent** (preferred if PD-L1 ≥50%; useful in certain circumstances if PD-L1 1-49%); or
- In combination with pemetrexed and either carboplatin or cisplatin for nonsquamous cell histology; or
- In combination with either carboplatin and either paclitaxel or albumin-bound paclitaxel for squamous cell histology; or
**Pembrolizumab (Keytruda) monotherapy can be considered for PD-L1 1-49% in individuals with poor PS or other contraindications to combination chemotherapy.
- Continuation maintenance therapy for recurrent, advanced or metastatic disease for PD-L1 expression positive (≥1%) tumors that are EGFR, ALK, ROS1, BRAF, MET exon 14 skipping mutation and RET negative*** and no contraindications to PD-1 or PD-L1 inhibitors and performance status 0-2, who achieve tumor response or stable disease following systemic or first-line therapy:
- As a single agent if pembrolizumab (Keytruda) monotherapy given first-line for nonsquamous cell histology; or
- In combination with pemetrexed if given first-line as part of a pembrolizumab/pemetrexed and either cisplatin or carboplatin regimen for nonsquamous cell histology; or
- As a single agent if pembrolizumab (Keytruda) was given as monotherapy or as part of a pembrolizumab/carboplatin/paclitaxel or albumin-bound paclitaxel regimen for squamous cell histology; or
- Treatment for recurrent, advanced or metastatic disease in combination with pemetrexed and either carboplatin or cisplatin (as preferred regimens if no contraindications to PD-1 or PD-L1 inhibitors for nonsquamous cell histology), in combination with carboplatin and either paclitaxel or albumin-bound paclitaxel (as preferred regimens if no contraindications to PD-1 or PD-L1 inhibitors for squamous cell histology) for individuals with performance status 0-1 as:
- Initial systemic therapy for EGFR, ALK, ROS1, BRAF, MET exon 14 skipping mutation, and RET negative*** and PD-L1 <1%; or
- First-line or subsequent therapy for BRAF V600E-mutation positive tumors; or
- First-line or subsequent therapy for NTRK gene fusion positive tumors; or
- First-line or subsequent therapy for MET exon 14 skipping mutation positive tumors; or
- First-line or subsequent therapy for RET rearrangement positive tumors; or
- Subsequent therapy for sensitizing EGFR mutation-positive tumors and prior erlotinib (with or without ramucirumab or bevacizumab), afatinib, gefitinib, osimertinib, or dacomitinib therapy; or
- Subsequent therapy for ALK rearrangement-positive tumors and prior crizotinib, ceritinib, alectinib or brigatinib therapy; or
- Subsequent therapy for ROS1 rearrangement-positive tumors and prior crizotinib, entrectinib or ceritinib therapy; or
- Single agent as subsequent therapy for recurrent, advanced, or metastatic disease in individuals with PS 0-2 and tumors with PD-L1 expression levels greater than or equal to 1% and no prior progression on a PD-1/PD-L1 inhibitor; or
*** if there is insufficient tissue to allow testing for all of EGFR, ALK, ROS1, BRAF, MET and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes.
Lung Cancer, NSCLC, Adenocarcinoma (with mixed subtypes), Large Cell Carcinoma (NCCN)
- Continuation maintenance therapy in combination with pemetrexed if given first line as part of a pembrolizumab/pemetrexed and either cisplatin or carboplatin regimen for recurrent, advanced, or metastatic disease and tumors of nonsquamous cell histology, in individuals with PS 0-2, who achieve tumor response or stable disease following initial systemic therapy; or
Lung Cancer, NSCLC, Squamous Cell Carcinoma (NCCN)
- Single-agent continuation maintenance therapy if given first line as part of a pembrolizumab/carboplatin/paclitaxel or albumin-bound paclitaxel regimen for recurrent, advanced, or metastatic disease and tumors of squamous cell histology, in individuals with PS 0-2 who achieve tumor response or stable disease following initial systemic therapy; or
Lung Cancer, Small Cell (FDA)
- Treatment of metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy; or
Lung Cancer, Small Cell, Small Cell Carcinoma (NCCN)
- Subsequent systemic therapy for individuals with PS 0-2 as a single agent for:
- Relapse within six (6) months following complete or partial response or stable disease with initial treatment; or
- Primary progressive disease; or
Lymphoma, B-Cell, Diffuse Large B-Cell Lymphoma (NCCN)
- Treatment as a single agent for individuals with relapsed or refractory primary mediastinal large B-cell lymphoma disease; or
Lymphoma, Extranodal Natural Killer T-Cell (NK/T-cell), Nasal Type (NCCN)
- For treatment of relapsed/refractory disease following additional therapy with an alternate combination chemotherapy regimen (asparaginase-based) not previously used, if a clinical trial is unavailable; or
Lymphoma, Hodgkin, Classic, cHL (FDA)
- Treatment of adult and pediatric individuals with:
- Refractory cHL; or
- Relapse after three (3) or more prior lines of therapy; or
Lymphoma, Hodgkin, Classic, cHL (NCCN)
- Treatment of individuals age 18 years or older as third-line or subsequent systemic therapy as a single agent for:
- Disease that has relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) with or without brentuximab vedotin; or
- Relapsed/refractory disease in individuals who are transplant-ineligible based on comorbidity or failure of second-line chemotherapy; or
- Post-allogeneic transplant; or
- Treatment of individuals greater than 60 years of age as palliative therapy as a single agent for:
- Disease that has relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) ± brentuximab vedotin; or
- Relapsed/refractory disease in individuals who are transplant-ineligible based on comorbidity or failure of second-line chemotherapy; or
- Post-allogeneic transplant; or
Lymphoma, Primary Mediastinal Large B-Cell (PMBCL) (FDA)
- Treatment of adult and pediatric individuals with:
- Refractory PMBCL; or
- Relapse after two (2) or more prior lines of therapy; or
Limitation of Use: pembrolizumab (Keytruda) is not recommended for treatment of individuals with PMBCL who require urgent cytoreductive therapy.
Lymphoproliferative Disorders, Primary Cutaneous CD30+ T-Cell (NCCN)
- Therapy for primary cutaneous anaplastic large cell lymphoma (ALCL) with multifocal lesions, or cutaneous ALCL with regional nodes (N1) (excludes systemic ALCL), as a single agent for relapsed/refractory disease; or
Melanoma (FDA)
- Treatment of individuals with unresectable or metastatic disease; or
- Adjuvant treatment of individuals with melanoma with involvement of lymph node(s) following complete resection; or
Melanoma – Cutaneous Melanoma (NCCN)
- Adjuvant treatment as a single agent:
- For resected stage III sentinel lymph node, SLN, positive disease during active nodal basin ultrasound surveillance or after CLND; or
- For stage III disease with clinically positive node(s) following wide excision of primary tumor and a complete therapeutic lymph node dissection; or
- For stage III disease with clinical satellite/in-transit metastases if no evidence of disease after initial treatment with local or regional therapy; or
- For local satellite/in-transit recurrence if no evidence of disease after complete excision to clear margins; or
- For local satellite in-transit recurrence if no evidence of disease after initial treatment with local or regional therapy; or
- Following total lymph node dissection and/or complete resection of nodal recurrence; or
- Following complete resection of distant metastatic disease; or
- First-line Single-agent therapy for metastatic or unresectable disease; or
- Second-line or subsequent therapy as a single agent for metastatic or unresectable disease after disease progression or maximum clinical benefit from BRAF targeted therapy:
- If anti-PD-1 checkpoint inhibitor immunotherapy was not previously used; or
- May be considered as re-induction therapy if prior checkpoint inhibitor immunotherapy resulted in disease control (complete response, partial response, or stable disease) and no residual toxicity, and disease progression/relapse occurred greater than three (3) months after treatment discontinuation; or
Melanoma, Uveal (NCCN)
- Consider as single agent therapy for distant metastatic disease; or
Merkel Cell Carcinoma, MCC (FDA)
- Treatment of adult and pediatric individuals with recurrent locally advanced or metastatic MCC; or
Merkel Cell Carcinoma, MCC (NCCN)
- Treatment if curative surgery and curative rational therapy are not feasible for:
- Individuals with recurrent locally advanced disease; or
- Individuals with recurrent regional disease; or
- Treatment for disseminated, clinical M1 disease with or without surgery and/or radiation therapy; or
Mesothelioma, Malignant Pleural, Epithelial, Sarcomatoid, Mixed (NCCN)
- Subsequent systemic therapy as a single agent; or
Microsatellite Instability-High, MSI-H, Cancer (FDA)
- Treatment of adult and pediatric individuals with unresectable or metastatic, MSI-H or mismatch repair deficient:
- 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 a fluoropyrimidine, oxaliplatin, and irinotecan; or
- First-line treatment of individuals with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC); or
Limitation of use: The safety and effectiveness of pembrolizumab (Keytruda) in pediatric individuals with MSI-H central nervous system cancers have not been established.
Mycosis Fungoides (MF)/Sezary Syndrome (SS) (NCCN)
- Primary systemic therapy for:
- Stage III MF; or
- Stage IV Sezary syndrome; or
- Systemic therapy as treatment for:
- Relapsed or persistent stage IA MF with B1 blood involvement, with or without skin-directed therapy; or
- Relapsed or persistent stage IB-IIA MFwith B1 blood involvement, with or without skin-directed therapy; or
- Stage IIB MF with limited tumor lesions refractory to multiple previous therapies, with or without skin-directed therapies; or
- Relapsed or refractory stage IIB MF with generalized tumor lesions, with or without skin-directed therapies; or
- Stage IIB MF with generalized tumor lesions that is refractory to multiple previous therapies or progression; or
- Relapsed or persistent stage III MF, with or without skin-directed therapies; or
- Stage III MF that is refractory to multiple previous therapies; or
- Relapsed or persistent stage IV SS; or
- Relapsed or persistent stage IV non Sezary or visceral disease (solid organ), with or without radiation therapy for local control; or
- Large cell transformation (LCT) with limited cutaneous lesions that is refractory to multiple previous therapies; or
- Relapsed or persistent LCT with generalized cutaneous or extracutaneous lesions, with or without skin-directed therapy; or
Neuroendocrine and Adrenal Tumors (NCCN)
- Treatment of metastatic adrenocortical carcinoma with or without mitotane; or
- Treatment for individuals with dMMR, MSI-H or advanced tumor mutational burden-high (TMB-H) poorly differentiated (high grade/large or small cell neuroendocrine and adrenal tumors that have progressed following prior treatment with no satisfactory alternative treatment options; or
Occult Primary – Adenocarcinoma or Carcinoma Not Otherwise Specified (NCCN)
- Used as a single agent (in individuals with MSI-H/dMMR tumors) in symptomatic individuals with PS 1-2 or asymptomatic individuals with PS 0 and aggressive disease for:
- Axillary involvement in men if clinically indicated; or
- Lung nodules or breast marker-negative pleural effusion; or
- Resectable liver disease; or
- Peritoneal mass or ascites with non-ovarian histology; or
- Retroperitoneal mass of non-germ cell histology in selected patients; or
- Unresectable liver disease or disseminated metastases; or
Ovarian, Epithelial/Fallopian Tube/Primary Peritoneal Cancers – Carcinosarcoma, Clear Cell, Endometrioid, Mucinous, Serous (NCCN)
- Single-agent therapy for persistent disease or recurrence, if MSI-H or dMMR:
- As immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy; or
- For progression on primary, maintenance, or recurrence therapy; or
- For stable or persistent disease (if not on maintenance therapy); or
- For complete remission and relapse less than six (6) months after completing chemotherapy; or
- For radiographic and/or clinical relapse in individuals with previous complete remission and relapse after greater than or equal to six (6) months after completing prior chemotherapy; or
Pancreatic Adenocarcinoma (NCCN)
- Treatment of individuals with MSI-H or dMMR tumors:
- As second-line therapy as a single agent for locally advanced or metastatic disease and disease progression; or
- First line therapy as a single agent for metastatic disease for individuals with poor PS; or
- Single agent for:
- Local recurrence in the pancreatic operative bed after resection; or
- Metastatic disease with or without local recurrence after resection if greater than or equal to six (6) months from completion of primary therapy; or
- Metastatic disease with or without local recurrence after resection if less than six (6) months from completion of primary therapy; or
Penile Cancer (NCCN)
- Single agent as subsequent-line systemic therapy if unresectable or metastatic, MSI-H or dMMR tumor that has progressed following prior treatment and no satisfactory alternative treatment options; or
Prostate Cancer – Adenocarcinoma (NCCN)
- Single-agent second-line or subsequent treatment (continue androgen deprivation therapy to maintain castrate levels of serum testosterone less than 50 ng/dL) for individuals who have progressed through at least one line of systemic therapy for castration-resistant distant metastatic (M1) disease that is MSI-H or dMMR, if pembrolizumab (Keytruda) not previously received; or
Prostate, Urothelial (Bladder) Carcinoma (NCCN)
- Therapy for metastatic disease as a single agent as:
- First-line systemic therapy in cisplatin ineligible individuals whose tumors express PD-L1 or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression; or
- Second line systemic therapy post-platinum; or
- Subsequent systemic therapy; or
Rectal Cancer – Adenocarcinoma (NCCN)
- Primary treatment as a single agent for unresectable metachronous metastases (deficient mismatch repair/microsatellite instability-high [dMMR/MSI-H] only) and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months; or
- Therapy as a single agent for individuals (dMMR/MSI-H only):
- For synchronous liver only and/or lung only metastases that are unresectable or medically inoperable and remain unresectable (with no progression of primary tumor) after primary systemic therapy; or
- Following palliative radiation therapy (RT) or chemo/RT for synchronous liver only and/or lung only metastases that are unresectable or medically inoperable and remain unresectable (with progression of primary tumor) after primary systemic therapy; or
- As primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for individuals with existing or imminent obstruction; or
- As primary treatment for synchronous unresectable metastases of other sites; or
- As primary treatment for unresectable metachronous metastases in individuals who have not received previous adjuvant FOLFOX or CapeOX within the past 12 months, who have received previous fluorouracil/leucovorin (5-FU/LV) or capecitabine therapy, or who have not received any previous chemotherapy; or
- For unresectable metachronous metastases that remain unresectable after primary treatment; or
- Therapy as a single agent for individuals (dMMR/MSI-H only)
- For synchronous liver only and/or lung only metastases that are unresectable or medically inoperable and remain unresectable (with no progression of primary tumor) after primary systemic therapy; or
- Following palliative RT or chemo/RT for synchronous liver only and/or lung only metastases that are unresectable or medically inoperable and remain unresectable (with progression of primary tumor) after primary systemic therapy; or
- As primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for individuals with existing or imminent obstruction; or
- As primary treatment for synchronous unresectable metastases of other sites; or
- As primary treatment for unresectable metachronous metastases in individuals who have not received previous adjuvant FOLFOX or CapeOX within the past 12 months, who have received previous fluorouracil/leucovorin (5-FU/LV) or capecitabine therapy, or who have not received any previous chemotherapy; or
- For unresectable metachronous metastases that remain unresectable after primary treatment; or
- Therapy as a single agent for individuals with advanced or metastatic disease (MMR/MSI-H only):
- As adjuvant treatment (following resection and/or local therapy) for resectable metachronous metastases in individuals who have received previous chemotherapy; or
- As adjuvant treatment for unresectable metachronous metastases that converted to resectable disease after primary treatment. Biologic therapy is only appropriate for continuation of favorable response from conversion therapy; or
- Subsequent therapy as a single agent (if no previous treatment with a checkpoint inhibitor) for advanced or metastatic disease (dMMR/MSI-H only), following previous oxaliplatin- irinotecan- and/or fluoropyrimidine-based therapy; or
Sarcoma, Soft Tissue (NCCN)
- Single-agent therapy for Alveolar Soft Part Sarcoma (ASPS); or
- Single agent for the treatment of metastatic undifferentiated pleomorphic sarcoma; or
Skin Cancer – Squamous Cell (NCCN)
- Treatment as a single agent for regional recurrent or distant metastases if curative surgery and curative radiation therapy are not feasible; or
Small Bowel Adenocarcinoma (NCCN)
- Subsequent therapy as a single agent for advanced or metastatic disease (dMMR/MSI-H only); or
- Initial therapy as a single agent for advanced or metastatic disease (dMMR/MSI-H only) in individuals with prior oxaliplatin exposure in the adjuvant setting or contraindication; or
Testicular Cancer – Nonseminoma, Pure Seminoma (NCCN)
- As single-agent third-line therapy in individuals with MSI-H/dMMR tumors; or
Thymic Carcinoma (NCCN)
- Second-line therapy for thymic carcinoma as a single agent for unresectable disease following first-line chemotherapy for potentially resectable locally advanced disease, solitary metastasis, or ipsilateral pleural metastasis; or
- Second-line therapy for thymic carcinoma as a single agent for extrathoracic metastatic disease; or
Tumor Mutational Burden-High (TMB-H) Cancer (FDA)
- Treatment of adult and pediatric individuals with unresectable or metastatic TMB-H [greater than or equal to 10 mutations/megabase (mut/Mb)] solid tumors, that have progressed following prior treatment and who have no satisfactory alternative treatment options; or
Limitations of Use: The safety and effectiveness of pembrolizumab (Keytruda) in pediatric individuals with TMB-H central nervous system cancers have not been established.
Thyroid Carcinoma – Anaplastic Carcinoma (NCCN)
- For tumor mutational burden-high (TMB-H) (≥10 mutations/megabase [mut/Mb]) tumors, used as single agent therapy:
- As aggressive first-line therapy for metastatic disease; or
- As second-line therapy for metastatic disease; or
Thyroid Carcinoma - Hürthle Cell Carcinoma (NCCN)
- For TMB-H (≥10 mutations/megabase [mut/Mb]) tumors, for treatment of:
- Unresectable locoregional recurrent or persistent disease not amenable to radioactive iodine (RAI) therapy; or
- Distant metastatic disease not amenable to RAI therapy; or
Thyroid Carcinoma – Medullary Carcinoma (NCCN)
- Treatment for TMB-H (≥10 mutations/megabase [mut/Mb]) tumors in:
- Unresectable locoregional disease that is symptomatic or progressing by RECIST criteria; or
- Asymptomatic recurrent or persistent distant metastases if unresectable and progressing by RECIST criteria; or
- Recurrent or persistent distant metastases if symptomatic disease or progression; or
Thyroid Carcinoma – Follicular Carcinoma (NCCN)
- For TMB-H (≥10 mutations/megabase [mut/Mb]) tumors, for treatment of:
- Unresectable locoregional recurrent or persistent disease not amenable to radioactive iodine (RAI) therapy; or
- Distant metastatic disease not amenable to RAI therapy; or
Thyroid Carcinoma – Papillary Carcinoma (NCCN)
- For TMB-H (≥10 mutations/megabase [mut/Mb]) tumors, consider for treatment of:
- Unresectable locoregional recurrent or persistent disease not amenable to radioactive iodine (RAI) therapy; or
- Distant metastatic disease not amenable to RAI therapy; or
Uterine Neoplasms – Uterine Sarcoma (NCCN)
- As single-agent therapy for individuals with unresectable or metastatic TMB-H [≥10 mutations/megabase (mut/Mb)] tumors, that have progressed following prior treatment and who have no satisfactory alternative treatment options; or
Uterine Neoplasms - Endometrial Carcinoma, Carcinosarcoma, Clear Cell Carcinoma, Endometrioid adenocarcinoma, Serous Carcinoma, Undifferentiated/dedifferentiated carcinoma
- Treatment of individuals with:
- Recurrent, metastatic, or high-risk MSI-H or dMMR tumors that have progressed following prior systemic therapy; or
- Unresectable or metastatic TMB-H (≥10 mutations/megabase [mut/Mb]) tumors, that have progressed following prior treatment and who have no satisfactory alternative treatment options; or
- Used in combination with lenvatinib for advanced or recurrent disease that is not MSI-H or dMMR in individuals who are not candidates for curative surgery or radiation and have progressed on prior systemic therapy; or
Vulvar Cancer, Squamous Cell Carcinoma (NCCN)
- As a single agent for advanced, recurrent, or metastatic disease:
- As second-line therapy for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors; or
- If disease progression on or after chemotherapy in individuals whose tumors express PD-L1 (Combined Positive Score ≥1); or
- In individuals with TMB-H (≥10 mutations/megabase [mut/Mb]) tumors, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
The use of pembrolizumab (Keytruda) is considered experimental/investigational and, therefore, non-covered for any other indication. Scientific evidence does not support the use for any other indication.
Procedure Codes