Highmark’s Medicare Advantage products have revised criteria for Programmed Death Receptor (PD-1)/ Programmed Death-Ligand (PD-L1) Blocking Antibodies as follows: Atezolizumab (Tecentriq)
Add the following indications: • Hepatocellular carcinoma • Melanoma
• Prostate Cancer
Update the following indications: • Bladder cancer
o Used 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
▪ For non-cystectomy candidates with stage IIIA (cT3, N0; cT4a, N0; cT1-4a, N1) disease if tumor is present upon reassessment of tumor status 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
o Used 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 down staging 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 • Non-small cell lung cancer
o Single agent as subsequent therapy for recurrent, advanced or metastatic disease in individuals with PS 0-2 and no prior progression on a PD-1/PD-L1 inhibitor; or
o Continuation maintenance therapy for recurrent, advanced or metastatic disease for PD-L1 expression positive (greater than or equal to 50%) 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 in individuals with performance status 0-2 who achieve a response or stable disease following first-line therapy with single agent atezolizumab (Tecentriq); or
o Treatment for recurrent, advanced, or metastatic disease as first-line therapy for PD-L1 expression positive (greater than or equal to 50%) 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; or
o Treatment for recurrent, advanced, or metastatic disease as first-line therapy for PD-L1 expression positive (greater than or equal to 1%) tumors that are EGFR, ALK negative or unknown and no contraindicaionts to the addition of pembrolizumab (Keytruda) or atezolizumab (Tecentriq) and performance status 0-2 in combination with carboplatin, paclitaxel, and bevacizumab for nonsquamous cell histology; or
o Continuation maintenance therapy as a single agent or in combination with bevacizumab for recurrent, advanced or metastatic disease for PD-L1 expression positive (greater than or equal to 1%) tumors that are EGFR ALK negative or unknown and no contraindications to the addition of
performance status 0-2 who achieve tumor response or stable disease following first-line therapy with
atezolizumab/carboplatin/paclitaxel/bevacizumab for nonsquamous cell histology; or
o Treatment for recurrent, advanced, or metastatic disease in combination with carboplatin, paclitaxel, and bevacizumab or in combination with carboplatin and albumin-bound paclitaxel for individuals with performance status (PS) 0- 1, no contraindications to PD-1 or PD-L1, and tumors of nonsquamous cell histology as:
▪ Initial systemic therapy for EGFR, ALK, ROS1, BRAF, MET exon 14 skipping mutation and RET negative and PDL1 less than 1%; 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
▪ First-line or subsequent therapy for BRAF V600E-mutation 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 or ceritinib therapy; or
o Continuation maintenance therapy in combination with bevacizumab for recurrent, advanced or metastatic disease and PD-L1 expression positive (greater than or equal to 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 in individuals with performance status 0-2 who achieve a response or stable disease following first-line therapy with atezolizumab/carboplatin/paclitaxel/bevacizumab for nonsquamous cell histology; or
o Continuation maintenance therapy for recurrent, advanced or metastatic disease for PD-L1 expression positive (greater than or equal to 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 in individuals with performance status 0-2 who achieve a response or stable disease following first-line therapy with atezolizumab/carboplatin/albumin- bound paclitaxel for nonsquamous cell histology; or
o Continuation maintenance therapy (if previously received first-line
atezolizumab/carboplatin/albumin-bound paclitaxel) for recurrent, advanced or metastatic disease, performance status 0-2, and tumors of nonsquamous cell histology in individuals who achieve tumor response or stable disease following initial systemic therapy; or
o Treatment for recurrent, advanced, or metastatic disease as first-line therapy for PD-L1 expression positive (greater than or equal to 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 for nonsquamous cell histology:
▪ in combination with bevacizumab, carboplatin and paclitaxel; or ▪ in combination with carboplatin and albumin-bound paclitaxel; or
o Continuation maintenance therapy as a single agent or in combination with bevacizumab (if previously received first-line
atezolizumab/carboplatin/paclitaxel/bevacizumab regimen) for recurrent, advanced or metastatic disease, performance status 0-2, and tumors of nonsquamous cell histology in individuals who achieve tumor response or stable disease following initial systemic therapy
Avelumab (Bavencio) Update bladder cancer
• Used as single-agent maintenance therapy if there is no progression on first-line platinum-containing chemotherapy with gemcitabine and either cisplatin or
carboplatin, or with DDMVAC (dose-dense methotrexate, vinblastine, doxorubicin, cisplatin); or
• Used as a single agent for recurrent or metastatic disease as second-line systemic therapy post-platinum
Nivolumab (Opdivo)
Add the following indications:
• Esophageal and esophagogastric junction cancers • Diffuse large B-cell lymphoma
• Neuroendocrine and adrenal tumors • Rectal cancer
Update the following indications:
• Central nervous system cancers – brain metastases
o Central Nervous System Cancers - Brain Metastases – Extensive
▪ Used as a single agent or in combination with ipilimumab for extensive
brain metastases in individuals with melanoma:
▪ As primary treatment in select individuals (eg, patients with small asymptomatic brain metastases); or
▪ As treatment for recurrent brain metastases in individuals with stable systemic disease or reasonable systemic treatment options; or ▪ Single-agent treatment for extensive brain metastases in individuals
with PD-L1 positive non-small cell lung cancer:
▪ May be considered as primary treatment in select individuals (eg, patients with small asymptomatic brain metastases); or
▪ As treatment for recurrent disease with stable systemic disease or reasonable systemic treatment options; or
o Central Nervous System Cancers - Brain Metastases – Limited
▪ Treatment of individuals with melanoma with limited brain metastases as single agent or in combination with ipilimumab:
• For initial treatment for brain metastases in select individuals (eg, individuals with small asymptomatic brain metastases); or • For recurrent brain metastases; or
• Treatment of relapsed disease with either stable systemic disease or reasonable systemic treatment options; or ▪ Used as single agent treatment for limited brain metastases in
• As initial treatment in select individuals (eg, patients with small asymptomatic brain metastases); or
• As treatment for recurrent brain metastases; or
• Treatment of relapsed disease with either stable systemic disease or reasonable systemic treatment options
• Colon cancer
o As primary treatment as a single agent or in combination with ipilimumab 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
o Therapy as a single agent or in combination with ipilimumab in individuals (dMMR/MSI-H only) who are not appropriate for intensive therapy:
▪ 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
o As therapy as a single agent or in combination with ipilimumab (dMMR/MSI-H only) who are not appropriate for intensive therapy:
▪ 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 individuals 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
o As subsequent therapy as a single agent or in combination with ipilimumab (if no previous treatment with a checkpoint inhibitor) (dMMR/MSI-H only)
following previous oxaliplatin- irinotecan- and/or fluoropyrimidine-based therapy
• Gestational Trophoblastic Neoplasia
o Single agent 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
• Head and neck cancer
o Treatment of individuals with recurrent or metastatic squamous cell
carcinoma of the head and neck with disease progression on or after a
platinum-based therapy; or
o As single agent subsequent therapy for nasopharyngeal cancer if previously
treated, recurrent or metastatic non-keratinizing disease in individuals with performance state 0-2 for:
▪ Recurrent/persistent disease with distant metastases; or
▪ Unresectable loco regional recurrence or second primary with prior radiation therapy (RT); or
o Systemic therapy as a single agent subsequent-line option, if immunotherapy not previously used, for non-nasopharyngeal cancer if disease progression on or after platinum therapy in:
▪ Performance status (PS) 0-1 and persistent or progressive metastatic disease at initial presentation following 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 radiation therapy (RT); or
▪ PS 3 and unresectable locoregional recurrence without prior RT • Hepatocellular carcinoma
o Treatment of individuals with HCC who have been previously treated with sorafenib, as a single agent or in combination with ipilimumab; or
o First-line treatment as a single agent for individuals ineligible for tyrosine kinase inhibitors [TKIs] or other anti-angiogenic agents who:
▪ 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
o Subsequent treatment as a single agent (Child-Pugh Class A or B only) or in combination with ipilmumab (Child-Pugh Class A only) for progressive
disease in individuals who have not been previously treated with a checkpoint inhibitor and:
▪ Are non-transplant candidates with unresectable disease; or ▪ Are inoperable by performance status or comorbidity, or have local
disease or local disease with minimal extrahepatic disease only; or ▪ Have extensive liver tumor burden; or
▪ Have metastatic disease • Non-small cell lung cancer
o Treatment of individuals 18 years of age or older with metastatic non-small cell lung cancer expressing PD-L1(greater than or equal to 1%), with no EGFR or ALK genomic tumor aberrations, as first-line treatment in combination with ipilimumab
o Individual 18 years of age or older with metastatic or recurrent non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations as first-line treatment, in combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy; or
o Metastatic NSCLC and progression on or after platinum-based
chemotherapy. Individuals with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab (Opdivo); or
o Treatment for recurrent, advanced or metastatic disease in combination with ipilimumab, in combination with ipilimumab, pemetrexed, and either
carboplatin or cisplatin for nonsquamous cell histology, or in combination with ipilimumab, paclitaxel and carboplatin for squamous cell histology for
individuals with performance status (PS) 0-1 and no contraindications to PD-1 or PD-L1 inhibitors as:
▪ Initial systemic therapy for EGFR, ALK, ROS1, BRAF, MET exon 14 skipping mutation, and RET negative* and PD-L1 less than 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
o Treatment of individuals with recurrent, advanced or metastatic NSCLC as single agent subsequent therapy in individuals with PS 0-2 and no prior progression on a PD-1/PD-L1 inhibitor; or
o Treatment for recurrent, advanced, or metastatic disease as first-line therapy for PD-L1 expression positive (greater than or equal to 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:
▪ In combination with ipilimumab; or
▪ In combination with ipilimumab, pemetrexed and either carboplatin or cisplatin for nonsquamous cell histology; or
▪ In combination with ipilimumab, paclitaxel and carboplatin for squamous cell histology; 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
o Activity against tumor mutational burden (TMB) as a single agent or in combination with ipilimumab
• Cutaneous melanoma
o As adjuvant therapy as a single agent:
▪ For resected stage III sentinel node positive disease during active nodal basin ultrasound surveillance or after complete lymph node dissection (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 /in-transit metastases if no evidence of disease after complete excision to clear margins or 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 if no evidence of disease after initial treatment with local or regional therapy; or
▪ Following therapeutic lymph node dissection and/or complete resection of nodal recurrence; or
▪ Following complete resection of distant metastatic disease; or o As First-line therapy as a single agent or in combination with ipilimumab for
o Preferred second-line or subsequent therapy for metastatic or unresectable disease after disease progression or maximum clinical benefit from BRAF targeted therapy:
▪ As a single agent or in combination with ipilmumab if checkpoint inhibitor immunotherapy was not previously used; or
▪ In combination with ipilimumab for individuals who progress on single- agent anti-PD-1 checkpoint inhibitor immunotherapy; or
▪ As re-induction therapy (as a single agent or in combination with ipilimumb) if prior anti-PD-1 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
• Small bowel adenocarcinoma
o Initial therapy as a single agent or in combination with ipilimumab for
advanced or metastatic disease (dMMR/MSI-H only) in individuals with prior oxaliplatin exposure in the adjuvant setting or contraindication; or
o Subsequent therapy as a single agent or in combination with ipilimumab for advanced or metastatic disease (dMMR/MSI-H only)
• Urothelial carcinoma
o Urothelial Carcinoma, Bladder Cancer
▪ Used 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 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 o Urothelial Carcinoma, Upper GU Tract Tumors
▪ Therapy for metastatic disease as a single agent for second-line systemic therapy post-platinum; or
o Urothelial Carcinoma, Locally Advanced or Metastatic
▪ Individuals with disease progression during or following platinum- containing chemotherapy; or
▪ Individuals with disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy; or o Urothelial Cancer, Urethra, Primary (Bladder)
▪ Single agent for recurrent or metastatic disease as second-line systemic therapy post-platinum (Note: Chemotherapy regimen based on histology)
Pembrolizumab (Keytruda) Add the following indications:
• Breast cancer
• Cutaneous squamous cell carcinoma • Squamous cell skin cancer
• Tumor mutational burden-high cancer Update the following indications:
• Urothelial carcinoma
o 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 o 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