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Durvalumab (Imfinzi®) and Tremelimumab-actl (Imjudo®)
MA08.123d

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.
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INDEX OF MEDICALLY NECESSARY INDICATIONS   

This policy addresses numerous medically necessary indications for the use of durvalumab (Imfinzi®) and tremelimumab-actl (Imjudo®) (listed in order of appearance within the Policy section). Please see below for the specific medical necessity criteria. (NOTE: Experimental/Investigational section below must also be reviewed.)

Type of Cancer
Subtype of Cancer
Ampullary Adenocarcinoma
Biliary Tract CancersGallbladder Cancer
Extrahepatic Cholangiocarcinoma
Intrahepatic Cholangiocarcinoma
Cervical Cancer

Esophageal and Esophagogastric Cancer

​Gastric Cancer
​
Hepatocellular Carcinoma 
Malignant Mesothelioma of Pleura 
Non-Small Cell Lung Carcinoma
Small Cell Lung Carcinoma
​​
MEDICALLY NECESSARY

AMPULLARY ADENOCARCINOMA
  • Durvalumab (Imfinzi), in combination with gemcitabine and cisplatin, is considered medically necessary and, therefore, covered as a first-line therapy for ampullary adenocarcinoma when the individual meets all of the following: 
    • Good Eastern Cooperative Oncology Group (ECOG) performance status (PS) (PS ​0-1)
    • Good biliary drainage
    • Adequate nutritional intake
    • Pancreatobiliary and mixed type disease with one of the following: 
      • Unresectable localized disease
      • Stage IV resected ampullary cancer
      • Metastatic disease at initial presentation​
    BILIARY TRACT CANCERS 
    Gallbladder Cancer​

    Durvalumab (Imfinzi), in combination with gemcitabine and cisplatin, is considered medically necessary and, therefore, covered for the treatment of gallbladder cancer for any of the following:  
    • As primary treatment for unresectable or resected gross residual (R2) disease, or metastatic disease (National Comprehensive Cancer Network [NCCN] preferred)
    • For individuals who developed recurrent disease more than 6 months after surgery with curative intent and more than 6 months after completion of adjuvant therapy (NCCN preferred) 
    • Subsequent treatment for progression on or after systemic treatment for unresectable or resected gross residual (R2) disease, or metastatic disease in those who have not been previously treated with a checkpoint inhibitor 
    • As neoadjuvant chemotherapy for resectable locally advanced disease that presents as ​one of the following:
      • ​Incidental finding of suspicious mass during surgery where hepatobiliary surgery expertise is unavailable
      • Incidental finding on pathologic review 
      • Mass on imaging ​​
    Intrahepatic and Extrahepatic Cholangiocarcinoma

    Durvalumab (Imfinzi), in combination with gemcitabine and cisplatin, is considered medically necessary and, therefore, covered for the treatment of intrahepatic and extrahepatic cholangiocarcinoma for any of the following:
    • As primary treatment for unresectable or resected gross residual (R2) disease, or metastatic disease (NCCN preferred) 
    • For individuals who developed recurrent disease more than 6 months after surgery with curative intent and more than 6 months after completion of adjuvant therapy (NCCN preferred) 
    • Subsequent treatment for progression on or after systemic treatment for unresectable or resected gross residual (R2) disease, or metastatic disease in those who have not been previously treated with a checkpoint inhibitor 
    CERVICAL CANCER

    Durvalumab (Imfinzi) is considered medically necessary and, therefore, covered for persistent, recurrent, or metastatic small cell neuroendocrine carcinoma of the cervix (NECC) when the individual meets both of the following: 

    • One of the following lines of therapy:
      • First-line
      • Second-line
      • Subsequent therapy (if not used previously as first line)
    • In combination with one of the following regimens, and continued as single agent for maintenance:
      • Cisplatin and etoposide
      • Carboplatin and etoposide
    ESOPHAGEAL AND ESOPHAGOGASTRIC JUNCTION CANCERS 
    Durvalumab (Imfinzi), in combination with tremelimumab-actl (Imjudo), is considered medically necessary and, therefore, covered as primary neoadjuvant immunotherapy for esophageal or esophagogastric junction adenocarcinoma if the tumor is microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) and the individual is medically fit for surgery with cT2, N0 (high-risk lesions: lymphovascular invasion, 3 cm or greater, poorly differentiated), cT1b-cT2, N+ or cT3-cT4a, any N disease

    GASTRIC CANCER 
    Durvalumab (Imfinzi), in combination with tremelimumab-actl (Imjudo), is considered medically necessary and, therefore, covered as primary neoadjuvant immunotherapy for gastric adenocarcinoma if the tumor is MSI-H or dMMR for potentially resectable locoregional disease (cT2 or higher, any N) if medically fit for surgery

    HEPATOCELLULAR CARCINOMA  (HCC) 
    D​​urvalumab (Imfinzi), as a single agent or in combination with tremelimumab-actl (Imjudo; NCCN preferred), is considered medically necessary and, therefore, covered for the treatment of HCC as first-line treatment for individuals with any of the following:  
    • Metastatic disease or extensive liver tumor burden
    • Unresectable disease and are not a transplant candidate
    • ​Liver-confined disease, inoperable by PS, comorbidity, or with minimal or uncertain extrahepatic disease​
    MALIGNANT MESOTHELIOMA OF PLEURA 
    Durvalumab (Imfinzi), in combination with pemetrexed and a platinum agent​, is considered medically necessary and, therefore, covered as first-line treatment of individuals with unresectable malignant mesothelioma of the pleura 

    NON-SMALL CELL LUNG CARCINOMA (NSCLC) 
    Durvalumab (Imfinzi), as a single agent, is considered medically necessary and, therefore, covered for the treatment of individuals with unresectable stage II-III NSCLC as consolidation immunotherapy when all of the following are met:
    • PS 0-1
    • No disease progression after definitive concurrent chemoradiation (for individuals who have received sequential chemoradiation, durvalumab [Imfinzi] can be considered as consolidation immunotherapy)
    • Histology demonstrates squamous cell carcinoma, adenocarcinoma (with mixed subtypes), or large cell carcinoma
    ​Durvalumab (Imfinzi), in combination with tremelimumab-actl (Imjudo), is considered medically necessary and, therefore, covered for the treatment of individuals with NSCLC with adenocarcinoma (with mixed subtypes), large cell carcinoma, or squamous cell carcinoma histology in one of the following scenarios:
    • As treatment for recurrent (excluding locoregional recurrence or symptomatic local disease but including mediastinal lymph node recurrence with prior radiation therapy), advanced, or metastatic diease as first-line therapy for programmed death ligand 1 (PD-L1) expression-positive (1-49 percent) tumors that are negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive) and no contraindications** to programmed death 1 (PD-1) or PD-L1 inhibitors and PS 0-2 in one of the following regimens:
      • With albumin-bound paclitaxel and carboplatin
      • With pemetrexed and either carboplatin or cisplatin for nonsquamous cell histology
      • With gemcitabine and either carboplatin or cisplatin for squamous cell histology
    • As treatment for recurrent (excluding locoregional recurrence or symptomatic local disease but including mediastinal lymph node recurrence with prior radiation therapy), advanced, or metastatic disease for individuals with PS 0-1 and no contraindications** to PD-1 or PD-L1 inhibitors when both of the following are met:
      • In one of the following regimens:
        • With albumin-bound paclitaxel and carboplatin
        • With pemetrexed and either carboplatin or cisplatin for nonsquamous cell histology
        • With gemcitabine and either carboplatin or cisplatin for squamous cell histology
      • In one of the following lines of therapy:
        • Initial systemic therapy for PD-L1 less than 1 percent and negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)
        • First-line therapy for EGFR exon 20 insertion mutation positive tumors
        • First-line or subsequent therapy for BRAF V600E mutation positive tumors
        • First-line or subsequent therapy for NTRK1/2/3 gene fusion positive tumors
        • First-line or subsequent therapy for MET exon 14 skipping mutation positive tumors
        • First-line or subsequent therapy for RET rearrangement positive tumors
        • First-line therapy for ERBB2 (HER2) mutation positive tumors
        • Subsequent therapy for EGFR exon 19 deletion or exon 21 L858R tumors and prior erlotinib with or without (ramucirumab or bevacizumab), afatinib, gefitinib, osimertinib, or dacomitinib therapy
        • Subsequent therapy for EGFR S768I, L861Q, and/or G719X mutation positive tumors and prior afatinib, osimertinib, erlotinib, gefitinib, or dacomitinib therapy
        • Subsequent therapy for ALK rearrangement positive tumors and prior crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib therapy
        • Subsequent therapy for ROS1 rearrangement positive tumors and prior crizotinib, entrectinib, repotrectinib, ceritinib, or lorlatinib therapy
    ​Durvalumab (Imfinzi), as a single agent, as continuation maintenance therapy for recurrent (excluding locoregional recurrence or symptomatic local disease but including mediastinal lymph node recurrence with prior radiation therapy), advanced, or metastatic disease, is considered medically necessary and, therefore, covered for the treatment of individuals with NSCLC with adenocarcinoma (with mixed subtypes), large cell carcinoma, or squamous cell carcinoma histology in one of the following scenarios:
    • As treatment for individuals with all of the following:​​
      • PD-L1 expression 1-49 percent tumors that are negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)
      • ​​​No contraindications** to PD-1 or PD-L1 inhibitors
      • PS 0-2
      • Have achieved a response or stable disease following first-line therapy with durvalumab (Imfinzi) and tremelimumab-actl (Imjudo) plus chemotherapy
    • As treatment for individuals with all of the following:
      • PD-L1 expression less than 1 percent tumors that are negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)
      • No contraindications** to PD-1 or PD-L1 inhibitors
      • PS 0-2
      • Have achieved a tumor response or stable disease following initial systemic therapy with durvalumab (Imfinzi) and tremelimumab-actl (Imjudo) plus chemotherapy
    Durvalumab (Imfinzi), in combination with pemetrexed, as continuation maintenance therapy for recurrent (excluding locoregional recurrence or symptomatic local disease but including mediastinal lymph node recurrence with prior radiation therapy), advanced, or metastatic disease, is considered medically necessary and, therefore, covered for the treatment of individuals with NSCLC with adenocarcinoma (with mixed subtypes) or large cell carcinoma histology in one of the following scenarios:
    • ​​As treatment for individuals with all of the following:
      • PD-L1 expression 1-49 percent tumors that are negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)
      • No contraindications** to PD-1 or PD-L1 inhibitors
      • PS 0-2
      • Have achieved a response or stable disease following first-line therapy with durvalumab (Imfinzi), tremelimumab-actl (Imjudo), and pemetrexed plus either carboplatin or cisplatin for nonsquamous cell histology
    • As treatment for individuals with all of the following:
      • PD-L1 expression less than 1 percent tumors that are negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)
      • No contraindications** to PD-1 or PD-L1 inhibitors
      • PS 0-2
      • Have achieved a tumor response or stable disease following initial systemic therapy with durvalumab (Imfinzi), tremelimumab-actl (Imjudo), and pemetrexed plus either carboplatin or cisplatin for nonsquamous cell histology 
    ​*Complete genotyping for EGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET, RET, and ERBB2 (HER2) via biopsy and/or plasma testing. If a clinically actionable marker is found, it is reasonable to start therapy based on the identified marker. Treatment is guided by available results and, if unknown, these individuals are treated as though they do not have driver oncogenes.

    **Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, and some oncogenic drivers (i.e., EGFR exon 19 deletion or exon 21 L858R, ALK rearrangements), have been shown to be associated with less benefit from PD-1/PD-L1 inhibitors​.
    ​
    SMALL CELL LUNG CARCINOMA (SCLC)
    Durvalumab (Imfinzi), ​in combination with etoposide and either carboplatin or cisplatin followed by single-agent maintenacne, is considered medically necessary and, therefore, covered for primary treatment (NCCN preferred) of extensive-stage small cell lung cancer (ES-SCLC) in individuals with any of the following:
    • ​​​Without localized symptomatic sites or brain metastases and good PS (PS 0-2)
    • Without localized symptomatic sites or brain metastases and poor PS (PS 3-4) due to SCLC
    • With localized symptomatic sites (used with radiation therapy [typically sequential] if spinal cord compression)
    • With brain metastases
    EXPERIMENTAL/INVESTIGATIONAL

    All other uses for durvalumab (Imfinzi) and tremelimumab-actl (Imjudo) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

    REQUIRED DOCUMENTATION

    The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

    The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

    Guidelines

    BENEFIT APPLICATION

    Subject to the terms and conditions of the applicable Evidence of Coverage, durvalumab (Imfinzi) and tremelimumab-actl (Imjudo) are covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

    THE EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS (PS)

    The Eastern Cooperative Oncology Group (ECOG), established in 1955, was one of the first groups to coordinate multicenter cancer clinical trials. The National Cancer Institute (NCI) is the primary funding source, and ECOG has evolved from a small consortium of institutions in the eastern United States to one of the largest clinical cancer research organizations in the country. As part of their work in the treatment of cancer, ECOG has developed the ECOG Performance Status (EPS), originally published in 1982 in the American Journal of Clinical Oncology. The use of the scales and the criteria in the EPS allows clinicians and researchers to determine an individual’s disease progression in terms of how the activities of daily living (ADL) are affected.
    ECOG Performance Status (PS)
    Grade
    ECOG
    0
    Fully active, able to carry on all pre-disease performance without restriction
    1
    Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (eg, light housework, office work)
    2
    Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50 percent of waking hours
    3
    Capable of only limited self-care, confined to bed or chair more than 50 percent of waking hours
    4
    Completely disabled. Cannot carry on any self-care: totally confined to bed or chair
    5
    Dead
    Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655.

    US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

    Durvalumab (Imfinzi) was approved by the FDA on May 1, 2017, for the treatment of individuals with locally advanced or metastatic urothelial carcinoma who either 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. Supplemental approvals for durvalumab (Imfinzi) have since been issued by the FDA. Durvalumab (Imfinzi) is administered as an intravenous infusion over 60 minutes. The FDA removed the indication for urothelial carcinoma from the drug labeling on July 15, 2021.

    Tremelimumab-actl (Imjudo), in combination with durvalumab (Imfinzi), was approved by the FDA on October 21, 2022, for the treatment of adult ​individuals with unresectable hepatocellular carcinoma (uHCC). On November 10, 2022, the FDA approved tremelimumab​​-actl (Imjudo), in combination with durvalumab (Imfinzi) and platinum-based chemotherapy, for adult individuals with metastatic non-small cell lung cancer (NSCLC) with no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

    PEDIATRIC USE
    The safety and effectiveness of durvalumab (Imfinzi) and tremelimumab-actl (Imjudo) have not been established in pediatric individuals.

    Description

    In a normal immune response, the body can recognize the presence of tumors and mount a response to eradicate them. The process of eradicating a tumor begins with antigen-presenting cells that gather and process the antigens released by tumors. This activates the T cells, which proliferate and attack the tumor.​

    Tumors have learned to evade the normal immune response by exploiting the immune checkpoint pathway. The programmed death receptor-1 (PD-1) is a checkpoint protein expressed on the membrane of activated T cells. The programmed death ligand-1 (PD-L1) and the programmed death ligand-2 (PD-L2) are checkpoint proteins expressed on tumor cells and tumor-infiltrating immune cells. When PD-L1 and PD-L2 attach to PD-1 receptors on the T cells, the T cells become inhibited and will not attack the tumor; thus, the tumor can continue to proliferate.

    Durvalumab (Imfinzi) is a human monoclonal antibody and immune checkpoint inhibitor that binds to PD-L1 on tumor cells and tumor-infiltrating immune cells and blocks the interaction with PD-1 and B7.1 receptors on T cells and antigen-presenting cells. Consequently, the tumor is no longer able to inactivate the T cells and the antitumor response continues.

    Cancers develop multiple strategies to evade immune detection and destruction by T cells. Cytotoxic T-lymphocytic-associated protein 4 (CTLA-4​) ​is a co-inhibitory molecule that functions to inhibit T cell activation. Antibodies that block the interaction of CTLA-4 with its ligands B7.1 and B7.2 can enhance immune responses, including antitumor immunity. Tremelimumab-actl (Imjudo) is a CTLA-4 blocking antibody allowing T cells to proliferate and attack the tumor. ​

    DURVALUMAB (IMFINZI) AND TREMELIMUMAB-ACTL (IMJUDO) INDICATIONS

    BILIARY TRACT CANCERS
    On September 2, 2022, the US Food and Drug Administration (FDA) approved durvalumab (Imfinzi), in combination with gemcitabine and cisplatin, as treatment for adults with locally advanced or metastatic biliary tract cancers.

    TOPAZ-1 (NCT03875235) was a multicenter, quadruple-blind, placebo-controlled, phase III study in which treatment-naïve individuals with unresectable or metastatic biliary tract cancers, or individuals with recurrent disease, were randomly assigned, in a 1:1 ratio, to receive either durvalumab (Imfinzi) or placebo, in combination with gemcitabine and cisplatin, followed by durvalumab (Imfinzi) or placebo as monotherapy, until there was either disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR).

    A total of 685 individuals were randomlized to either durvalumab (Imfinzi) (n=341) or placebo (n=344) in combination with gemcitabine and cisplatin. At the time of data cutoff, 198 participants (58.1 percent) in the durvalumab (Imfinzi) cohort and 226 participants (65.7 percent) in the placebo cohort had died. The median OS was 12.8 months in the durvalumab (Imfinzi) cohort and 11.5 months in the placebo cohort (p=0.021). Median PFS was 7.2 months in the durvalumab (Imfinzi) cohort and 5.7 months in the placebo cohort (​p=0.001). The ORR was 26.7 percent in the durvalumab (Imfinzi) cohort and 18.7 percent in the placebo cohort. The median DOR at 12 months was 26.1 percent in the durvalumab (Imfinzi) cohort and 15.percent in the placebo cohort. The incidence of grade 3 or 4 adverse events was 75.7 percent in the durvalumab (Imfinzi) cohort and 77.8 percent in the placebo cohort.

    HEPATOCELLULAR CARCINOMA (HCC)
    On October 24, 2022, the FDA approved durvalumab (Imfinzi​), in combination with tremelimumab-actl (Imjudo), for the treatment of adults with unresectable HCC. The Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen consists of a single dose of tremelimumab-actl (Imjudo), plus durvalumab (Imfinzi), followed by durvalumab (Imfinzi) every four weeks.

    Approval of the combination regimen was based on the results from the phase III, multicenter, open-label HIMALAYA trial (NCT03298451), in which a total of 1171 participants were randomized to durvalumab (Imfinzi; arm 1; n=389),  STRIDE (arm 2; n=393), or the standard of care treatment, sorafenib (Nexavar; arm 3; n=389). The primary endpoint was OS in arm 2 versus arm 3. Secondary endpoints included OS in arm 1 versus arm 3, PFS, time to progression (TTP), ORR, and DOR.

    The median OS was 16.56 months in arm 1, 16.43 months in arm 2, and 13.77 months in arm 3. PFS was 3.65 months in arm 1, 3.78 months in arm 2, and 4.07 months in arm 3. The median TTP was 3..8 months in arm 1, 5.4 months in arm 2, and 5.6 months in arm 3. The ORR was 17 percent in arm 1, 20.1 percent in arm 2, and 3.1 percent in arm 3. The median DOR was 16.8 months in arm 1, 22.3 months in arm 2, and 18.4 months in arm 3.

    NON-SMALL CELL LUNG CANCER ​(NSCLC)
    On February 16, 2018, the FDA approved durvalumab (Imfinzi) for individuals with unresectable stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

    The efficacy and safety of durvalumab (Imfinzi) was evaluated in the PACIFIC study (NCT02125461), a multicenter, randomized, double-blind, placebo-controlled phase III study in individuals with unresectable stage III NSCLC who completed at least two cycles of concurrent platinum-based chemotherapy and definitive radiation within 42 days prior to initiation of the study drug and had an ​Eastern Cooperative Oncology Group (ECOG) performance status​ (PS) of 0 or 1. Individuals were randomizedin a 2:1 ratio to receive durvalumab (Imfinzi) or placebo every two weeks for up to a year or until unacceptable toxicity or confirmed progression. The primary efficacy endpoints were PFS and OS. Secondary endpoints included ​ORR and DOR.

    A total of 713 individuals underwent randomization. A total of 473 individuals received durvalumab (Imfinzi) and a total of 236 individuals received placebo. As of the interim analysis, the median follow-up was 25.2 months. The 24-month OS rate was 66.3 versus 55.6 percent in the durvalumab (Imfinzi) group versus the placebo group (p=0.005). The median PFS was 17.2 versus 5.6 months in the durvalumab (Imfinzi) group versus the placebo group. The ORR was 30 versus 17.8 percent of individuals who attained a complete or partial response in the durvalumab (Imfinzi) group versus the placebo group. The total number of individuals who sustained a grade 3 or 4 adverse event was 30.5 versus 26.1 percent in the durvalumab (Imfinzi) group versus the placebo group.​

    On November 10, 2022, the FDA approved tremelimumab-actl (Imjudo), in combination with durvalumab (Imfinzi) and platinum-based chemotherapy, for the treatment of adults with metastatic non-small cell lung cancer (mNSCLC) without epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

    The efficacy and safety of tremelimumab-actl (Imjudo), in combination with durvalumab (Imfinzi) and platinum-based chemotherapy, was evaluated in the phase III POSEIDON study (NCT03164616), a randomized, multicenter, open-label comparative study for first-line treatment in individuals with mNSCLC. The POSEIDON study evaluated tremelimumab-actl (Imjudo) plus durvalumab (Imfinzi) and chemotherapy (arm 1) versus durvalumab (Imfinzi) plus chemotherapy (arm 2) versus chemotherapy alone (arm 3) as first-line treatment for mNSCLC. Participants (n=1013) with EGFR/ALK wild-type mNSCLC were randomized (1:1:1) to the three arms. The primary endpoints were PFS and OS in arm 2 versus arm 3. Secondary endpoints included PFS and OS for arm 1 versus arm 3, ORR, and DOR.

     The median PFS was significantly improved in arm 2 versus arm 3 (hazard ration [HR], 0.74; 95 percent confidence interval [CI], 0.62–0.89; p=0.0009; 5.5 versus 4.8 months). Although median OS in arm 2 was better than in arm 3, it did not reach statistical significance (HR, 0.86; 95 percent CI, 0.72–1.02; p=0.0758; 13.3 vs. 11.7 months). The median 24-month OS for arm 2 versus arm 3 was 29.6 versus 22.1 percent. The median PFS for arm 1 versus arm 3 was 6.2 versus 4.8 months (HR, 0.72; 95 percent CI, 0.60–0.86; p=0.0003). The median OS for arm 1 versus arm 3 was 14.0 versus 11.7 months (HR, 0.77; 95 percent CI, 0.65–0.92; p=0.0030). The 24-month OS was significantly improved in arm 1 versus arm 3, (32.9 vs. 22.1 percent). Treatment-related adverse events (TRAE) were maximum grade 3 or 4 in 51.8, 44.6, and 44.4 percent of participants in arm 1, arm 2, and arm 3 respectively. The percentage of participants that discontinued treatment due to TRAEs was 15.5, 14.1, and 9.9 percent, in arm 1, arm 2, and arm 3, respectively.

    SMALL CELL LUNG CANCER ​(SCLC)
    On March 27, 2020, the FDA granted approval for durvalumab (Imfinzi), in combination with etoposide and either carboplatin or cisplatin, as first-line treatment of individuals with extensive-stage small cell lung cancer (ES-SCLC).

    The efficacy and safety of durvalumab (Imfinzi), in combination with etoposide and either carboplatin or cisplatin, in previously untreated ES-SCLC was investigated in the CASPIAN study (NCT03043872)​, a randomized, multicenter, active-controlled, phase III, open-label trial. Participants were randomly assigned to one of three arms. Individuals in arm 1 received durvalumab (Imfinzi), tremelimumab-actl (Imjudo), a platinum-containing chemotherapy (either carboplatin or cisplatin), and etoposide. Individuals in arm 2 received durvalumab (Imfinzi) plus a platinum-containing chemotherapy (either carboplatin or cisplatin), and etoposide. Individuals in arm 3 received a platinum-containing chemotherapy (either carboplatin or cisplatin) and etoposide. The primary endpoint was OS in arm 1 versus arm 3 and arm 2 versus arm 3. Secondary endpoints were PFS and ORR.

    A total of 805 individuals underwent randomization; 268 individuals in arm 1, 268 individuals in arm 2, and 269 individuals in arm 3. The OS was 10.4 months in arm 1 versus 12.9 months in arm 2 versus 10.5 months in arm 3. Median PFS was 4.9 months in arm 1 versus 5.1 months in arm 2 versus 5.4 months in arm 3. The ORR was 74.2 percent in arm 1 versus 79.5 percent in arm 2 versus 70.6 percent in arm 3.​

    There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company's off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.​​​

    References

    Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022;1(8):EVIDoa2100070.

    American Hospital Formulary Service (AHFS). Durvalumab (Imfinzi®). AHFS Drug Information 2024. [UpToDate Lexidrug Web site]. 12/12/2023. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed March 13, 2024.

    American Hospital Formulary Service (AHFS). Tremelimumab-actl (Imjudo®). AHFS Drug Information 2024. [UpToDate Lexidrug Web site]. 01/31/2024. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed March 13, 2024.

    Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379(24):2342-2350.

    ClinicalTrials.gov. A global study to assess the effects of MEDI4736 following concurrent chemoradiation in patients with stage III unresectable non-small cell lung cancer (PACIFIC). ClinicalTrials.gov Identifier: NCT02125461. First Posted: April 29, 2014. Last Update Posted: October 10, 2023. Available at: https://clinicaltrials.gov/. Accessed March 13, 2024.

    ClinicalTrials.gov. Durvalumab +/- tremelimumab in combination with platinum based chemotherapy in untreated extensive-stage small cell lung cancer (CASPIAN). ClinicalTrials.gov Identifier: NCT03043872. First Posted: February 6, 2017. Last Update Posted: December 21, 2023. Available at: https://clinicaltrials.gov/. Accessed March 13, 2024.

    ClinicalTrials.gov. Durvalumab or placebo in combination with gemcitabine/cisplatin in patients with 1st line advanced biliary tract cancer (TOPAZ-1). ClinicalTrials.gov Identifier: NCT03875235. First Posted: March 14, 2019. Last Update: February 26, 2024. Available at: https://clinicaltrials.gov/. Accessed March 13, 2024.

    ClinicalTrials.gov. Study of durvalumab and tremelimumab as first-line treatment in patients with advanced hepatocellular carcinoma (HIMALAYA). ClinicalTrials.gov Identifier: NCT03298451. First Posted: October 2, 2017. Last Update Posted: January 12, 2024. Available at: https://clinicaltrials.gov/. Accessed March 13, 2024.

    ClinicalTrials.gov. Study of durvalumab and tremelimumab with chemotherapy or durvalumab with chemotherapy or chemotherapy alone for patients with lung cancer (POSEIDON). ClinicalTrials.gov Identifier: NCT03164616. First Posted: May 23, 2017. Last Update: March 5, 2024. Available at: https://clinicaltrials.gov/. Accessed March 13, 2024.

    ClinicalTrials.gov. Study of durvalumab with chemoradiotherapy for women with locally advanced cervical cancer (CALLA). ClinicalTrials.gov Identifier: NCT03830866. First Posted February 5, 2019. Last Update Posted: August 1, 2023. Available at: https://clinicaltrials.gov/. Accessed March 13, 2024.

    Durvalumab (Imfinzi®) Package Insert. Wilmington, DE : AstraZeneca Pharmaceuticals LP. 06/2023. Available at: https://www.imfinzi.com/. Accessed March 13, 2024.

    Elsevier's Clinical Pharmacology Compendium. Durvalumab (Imfinzi®). [Clinical Key Web site]. 09/28/2023. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed March 13, 2024.

    Elsevier's Clinical Pharmacology Compendium. Tremelimumab-actl (Imjudo®). [Clinical Key Web site]. 09/28/2023. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed March 13, 2024.

    Goldman JW, Dvorkin M, Chen Y, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomized, controlled, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):51-65.

    Johnson ML, Cho BC, Luft A, et al. Durvalumab with or without tremelimumab in combination with chemotherapy as first-line therapy for metastatic non-small-cell lung cancer: the phase III POSEIDON study. J Clin Oncol. 2023;41(6):1213-1227.

    Merative Micromedex® DRUGDEX® (electronic version). Durvalumab (Imfinzi®). [Micromedex Web site]. 02/28/2024. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 13, 2024.

    Merative Micromedex® DRUGDEX® (electronic version). Tremelimumab-actl (Imjudo®). [Micromedex Web site]. 02/28/2024. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 13, 2024.

    National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® -  Ampullary Adenocarcinoma. V1.2024. [NCCN Web site]. 12/13/2024. Available from: https://www.nccn.org/professionals/physician_gls/pdf/ampullary.pdf. Accessed March 13, 2024.

    National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® -  Biliary Tract Cancers. V3.2023. [NCCN Web site]. 11/08/2023. Available from: https://www.nccn.org/professionals/physician_gls/pdf/btc.pdf. Accessed March 13, 2024.

    National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Cervical Cancer. V2.2024. [NCCN Web site]. 02/23/2024. Available from: https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf. Accessed March 13, 2024.
      
    National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Esophageal and Esophagogastric Junction Cancers. V4.2023. [NCCN Web site]. 01/26/2024. Available from: https://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf. [via subscription only]. Accessed March 13, 2024.

    National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Gastric Cancer. V3.2023. [NCCN Web site]. 01/26/2024. Available from: https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf. [via subscription only]. Accessed March 13, 2024.

    National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® –Hepatocellular Carcinoma. V2.2023. [NCCN Web site]. 09/14/2023. Available from: https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf. [via subscription only].  Accessed March 13, 2024.

    National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® – Non-Small Cell Lung Cancer. V2.2024. [NCCN Web site]. 02/09/2024. Available from: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. [via subscription only]. Accessed March 13, 2024.

    National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® – Small Cell Lung Cancer. V2.2024 [NCCN Web site]. 11/21/2023. Available from: https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. [via subscription only].  Accessed March 13, 2024.

    National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium®. [NCCN Web site]. Durvalumab (Imfinzi®). Available at: https://www.nccn.org/professionals/drug_compendium/content/ [via subscription only]. Accessed March 13, 2024.

    National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium®. [NCCN Web site]. Tremelimumab-actl (Imjudo®). Available at: https://www.nccn.org/professionals/drug_compendium/content/ [via subscription only].  Accessed March 13, 2024.

    National Institute for Health and Care Excellence (NICE). TA944: Durvalumab with gemcitabine and cisplatin for treating unresectable or advanced biliary tract cancer. [NICE Web site]. Available at: https://www.nice.org.uk/guidance/ta944. Accessed March 13, 2024.

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    Coding

    CPT Procedure Code Number(s)
    N/A
    ICD - 10 Procedure Code Number(s)
    N/A
    ICD - 10 Diagnosis Code Number(s)
    See Attachment A.
    HCPCS Level II Code Number(s)
    J9173 Injection, durvalumab, 10 mg

    J9347 Injection, tremelimumab-actl, 1 mg​​
    Revenue Code Number(s)
    N/A


    Coding and Billing Requirements

    Policy History

    5/6/2024
    5/6/2024
    MA08.123
    Medical Policy Bulletin
    Medicare Advantage
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    No