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Durvalumab (Imfinzi®) and tremelimumab-act (Imjudo®)
MA08.123c

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.

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).

Types of Cancer
Subtype of Cancer
AmpullaryAadenocarcinoma
Pancreatobilliary and mixed type
Cervical CancerSmall cell neuroendocrine carcinoma of the cervix
Hepatobiliary Cancers- Biliary Tract CancersExtrahepatic Cholangiocarcinoma
 Gallbladder Cancer
 Intrahepatic Cholangiocarcinoma
Hepatocellular Carcinoma 
Malignant Mesothelioma of Pleura 
Non-Small Cell Lung CarcinomaAdenocarcinoma (with mixed subtypes)
 Large cell carcinoma
 Squamous cell carcinoma
Small Cell Lung CarcinomaExtensive-stage small cell lung cancer
​
MEDICALLY NECESSARY

AMPULLARY ADENOCARCINOMA

  • Durvalumab (Imfinzi) is considered medically necessary and, therefore, covered as a first-line therapy when the individual meets all of the following criteria: 
    • good performance status (ECOG  [Eastern Cooperative Oncology Group]  0-1 with good biliary drainage and adequate nutritional intake)
    • in combination with gemcitabine and cisplatin
    • pancreatobiliary and mixed type disease 
    • one of the following stages:
      • unresectable localized disease
      • stage IV resected ampullary cancer
      • metastatic disease at initial presentation​

CERVICAL CANCER

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

    • one of the following therapies:
      • first-line therapy
      • second-line therapy
      • subsequent therapy (if not used previously as a first line therapy)
    • In combination with one of the following regimens:
      • cisplatin and etoposide
      • carboplatin and etoposide

HEPATOBILIARY CANCERS

Biliary Tract Cancers: Gallbladder Cancer, Intrahepatic Cholangiocarcinoma, Extrahepatic Cholangiocarcinoma
Durvalumab (Imfinzi) is considered medically necessary and, therefore, covered for the treatment of the following biliary cancers: gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma in combination with cisplatin and gemcitabine as a treatment (National Comprehensive Cancer Network [NCCN]-preferred regimen) for any one of the following: 

  •  As the primary treatment for unresectable, or resected gross residual (R2) disease,  or metastatic disease 
  • For individuals​ who developed recurrent disease >6 months after surgery with curative intent and >6 months after completion of adjuvant therapy 
  • 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
  • In Gallbladder Cancer as neoadjuvant chemotherapy for resectable locally advanced disease that presents as any of the following:
    • ​incidental finding of suspicious mass during surgery where hepatobiliary surgery expertise unavailable
    • incidental finding on pathologic review
    • mass on imaging ​

HEPATOCELLULAR CARCINOMA 
Durvalumab (Imfinzi) is considered medically necessary and, therefore, covered for the treatment of adults with unresectable hepatocellular carcinoma (uHCC) in combination with tremelimumab-actl (Imjudo).


Durvalumab (Imfinzi) is considered medically necessary and, therefore, covered for the treatment of hepatocellular carcinoma as a first-line, single-agent treatment (NCCN-preferred regimen) for individuals with any one of the following:   

  • With metastatic disease or extensive liver tumor burden
  • With unresectable disease and are not a transplant candidate
  • With liver-confined disease, inoperable by performance status, comorbidity or minimal or uncertain extrahepatic disease​​
MALIGNANT MESOTHELIOMA OF PLEURA
Durvalumab (Imfinzi) is considered medically necessary and, therefore, covered as a first line treatment of adults with unresectable malignant mesothelioma of pleura in combination with pemetrexed and a platinum agent.​

NON-SMALL CELL LUNG CARCINOMA (NSCLC)
Durvalumab (Imfinzi) in combination with tremelimumab-actl (Imjudo) and platinum-based chemotherapy​ is considered medically necessary and, therefore, covered for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
​

Durvalumab (Imfinzi) is considered medically necessary and, therefore, covered for the treatment of individuals with NSCLC with any of the following histology: Adenocarcinoma (with mixed subtypes), Large cell carcinoma , Squamous cell carcinoma (not including locoregional recurrence or symptomatic local disease with no evidence of disseminated disease)   when one of the following criterion are met:

  • Consolidation immunotherapy for those with unresectable stage II-III disease, performance status (PS) 0-1, and no disease progression after definitive concurrent chemoradiation
  • Recurrent, advanced, or metastatic disease as first-line therapy for PD-L1 expression-positive (between 1 -and 49 percent nonsquamous cell or squamous cell histology) tumors when all of the following criteria are met:  
    • ​​​​Tumor is negative for actionable molecular biomarkers*
    • ​There are no contraindications** to PD-1 or PD-L1 inhibitors
    • ​Individual has a performance status of 0-2
    • In combination with one of the following:
      • tremelimumab-actl, albumin-bound paclitaxel, and carboplatin
      • tremelimumab-actl, pemetrexed, and either carboplatin or cisplatin for nonsquamous cell histology
      • ​​tremelimumab-actl, gemcitabine, and either carboplatin or cisplatin for squamous cell histology
  • ​Continuation maintenance therapy as a single agent for recurrent, advanced, or metastatic disease for PD-L1 expression positive (between 1 and 49 percent nonsquamous cell or squamous cell histology) tumors when all of the following criteria are met:
    • ​Tumor is negative for actionable molecular biomarkers*
    • There are no contraindications** to PD-1 or PD-L1 inhibitors 
    • Individual has a performance status 0-2
    • Individual has achieved a response or stable disease following first-line therapy with durvalumab/tremelimumab-actl plus chemotherapy
  • Treatment for recurrent, advanced, or metastatic disease for individuals with performance status 0-1 and no contraindications** to PD-1 or PD-L1 inhibitors symptomatic local disease with no evidence of disseminated disease)  in combination with one of the following:
    • tremelimumab-actl, albumin-bound paclitaxel, and carboplatin
    • tremelimumab-actl, pemetrexed, and either carboplatin or cisplatin for nonsquamous cell histology
    • tremelimumab-actl, gemcitabine, and either carboplatin or cisplatin for squamous cell histology
    • ​​​The above regimens are used as:
      • initial systemic therapy for PD-L1 <1% and negative for actionable molecular biomarkers*
      • first-line therapy for EGFR exon 20 mutation positive tumors
      • first-line therapy for KRAS G12C mutation positive tumors
      • first-line or subsequent therapy for BRAF V600E mutation positive tumors
      • first-line (useful in certain circumstances) or subsequent therapy for NTRK1/2/3 gene fusion positive tumors
      • first-line (useful in certain circumstances) 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 +/- (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
      • ​s​​​ubsequent therapy for ROS1 rearrangement positive tumors and prior crizotinib, entrectinib, or ceritinib therapy
  • Continuation maintenance therapy as a single agent for recurrent, advanced, or metastatic disease with PD-L1 expression <1% tumors when all of the following criteria are met: 
    • Tumor is negative for actionable molecular biomarkers*
    • There are no contraindications** to PD-1 or PD-L1 inhibitors 
    • Individual has a performance status 0-2
    • ​Individual has achieved a response or stable disease following initial systemic therapy with durvalumab/tremelimumab-actl plus chemotherapy​

Durvalumab (Imfinzi) is considered medically necessary and, therefore, covered for the treatment of individuals with NSCLC with any of the following histology: Adenocarcinoma (with mixed subtypes), Large cell carcinoma (not including locoregional recurrence or symptomatic local disease with no evidence of disseminated disease)  when one of the following criterion are met:

  • Continuation maintenance therapy in combination with pemetrexed for recurrent, advanced, or metastatic disease for PD-L1 expression positive (between 1 and 49percent) tumors when all of the following are met:  
    • Tumor is negative for actionable molecular biomarkers*
    • There are no contraindications** to PD-1 or PD-L1 inhibitors 
    • Individual has a performance status 0-2

    • Individual has achieved a response or stable disease following first-line therapy with durvalumab/tremelimumab-actl/pemetrexed with either carboplatin or cisplatin for nonsquamous cell histology​

  • Continuation maintenance therapy in combination with pemetrexed for recurrent, advanced, or metastatic disease with PD-L1 expression <1% tumors when all of the following are met: 
    • Tumor is negative for actionable molecular biomarkers*
    • There are no contraindications** to PD-1 or PD-L1 inhibitors 
    • Individual has a performance status 0-2

    • Individual has achieved a response or stable disease following first-line therapy with durvalumab/tremelimumab-actl/pemetrexed with either carboplatin or cisplatin for nonsquamous cell histology

*if there is insufficient tissue to allow testing for all of EGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET, RET, and ERBB2 (HER2), repeat biopsy and/or plasma testing should be done. If these are not feasible, 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 (ie, 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) is considered medically necessary and, therefore, covered for the treatment of extensive-stage small cell lung cancer (ES-SCLC) in combination with etoposide and either carboplatin or cisplatin, as first-line treatment (​NCCN-preferred regimen) followed by single-agent maintenance in individuals with any one of the following:
  • With localized symptomatic sites
  • Without localized symptomatic sites or brain metastases and the individual has an ECOG performance status (PS) 0-2
  • With brain metastases
  • Without localized symptomatic sites or brain metastases and the individual has an ECOG PS 3-4 due to the cancer​​
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) is 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

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
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 house work, 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):649-55.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Durvalumab (Imfinzi) was approved by the FDA on May 1, 2017, for the treatment 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 treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). On November 10, 2022, the FDA approved tremelimumab (Imjudo) in combination with durvalumab (Imfinzi) and platinum-based chemotherapy for adult patients 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 block 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. CTLA-4 (cytotoxic T-lymphocytic-associated protein 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 anti-tumor 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 CANCER


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


TOPAZ-1( NCT03875235) was a double-blind, placebo-controlled, phase 3 study in which participants with previously unresectable or metastatic biliary tract cancer or with recurrent disease were randomly assigned in a 1:1 ratio to receive durvalumab or placebo in combination with gemcitabine plus cisplatin for up to eight cycles, followed by durvalumab or placebo monotherapy until disease progression or unacceptable toxicity. Randomization was stratified by disease status (initially unresectable vs. recurrent) and primary tumor location (intrahepatic cholangiocarcinoma vs. extrahepatic cholangiocarcinoma vs. gallbladder cancer).


Overall, 685 participants were randomly assigned to durvalumab (n=341) or placebo (n=344) with chemotherapy. As of data cutoff, 198 participants (58.1%) in the durvalumab group and 226 participants (65.7%) in the placebo group had died. The hazard ratio for overall survival was 0.80 (95% confidence interval [CI], 0.66–0.97; P=0.021). The estimated 24-month overall survival rate was 24.9% (95% CI, 17.9–32.5) for durvalumab and 10.4% (95% CI, 4.7–18.8) for placebo. The hazard ratio for progression-free survival was 0.75 (95% CI, 0.63–0.89; P=0.001). Objective response rates were 26.7% with durvalumab and 18.7% with placebo. The incidences of grade 3 or 4 adverse events were 75.7% and 77.8% with durvalumab and placebo, respectively.


HEPATOCELLULAR CARCINOMA (HCC)


On October 24, 2022, the FDA approved durvalumab (Imfinizi) in combination with tremelimumab (Imjudo) for the treatment of adults with unresectable hepatocellular carcinoma. The Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen consists of a single dose of Imjudo 300 mg plus Imfinzi 1500 mg, followed by Imfinzi every 4 weeks.


Approval of the combination regimen was based on the results from the phase 3 open-label HIMALAYA trial, in which a total of 1171 participants were randomly assigned to STRIDE (n=393), Imfinzi (n=389), or the standard of care, sorafenib (Nexavar) (n=389).


The median overall survival was 16.43 months (95% CI, 14.16–19.58) with STRIDE, 16.56 months (95% CI, 14.06–19.12) with Imfinzi, and 13.77 months (95% CI, 12.25–16.13) with sorafenib. Overall survival at 3 years was 30.7%, 24.7%, and 20.2%, respectively. Participants receiving the STRIDE regimen experienced a 22% reduction in the risk of death versus sorafenib monotherapy (hazard ratio, 0.78; P=0.0035).


NON-SMALL CELL LUNG CARCINOMA ​(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 of durvalumab (Imfinzi) was evaluated in the PACIFIC study (NCT02125461), a multicenter, randomized, double-blind, placebo-controlled phase 3 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. The study excluded individuals who had progressed following concurrent chemoradiation, individuals with active or prior documented autoimmune disease within 2 years of initiation of the study or individuals with medical conditions that required systemic immunosuppression. Randomization was stratified by sex, age (<65 years vs 65 years ​or older), and smoking history (smoker vs nonsmoker). Individuals were randomly assigned 2:1 to receive durvalumab (Imfinzi) 10 mg/kg or placebo intravenously every 2 weeks for up to 12 months or until unacceptable toxicity or confirmed Response Evaluation Criteria in Solid Tumors (​RECIST) 1.1-defined progression. Assessment of tumor status was performed every 8 weeks. The major efficacy outcome measures were progression-free survival (PFS) as assessed by a Blinded Independent Central Review (​BICR) RECIST 1.1, and overall survival (OS). Additional efficacy outcome measures included objective response rate (​ORR) and duration of response (DOR) assessed by BICR.

Of the 713 individuals who underwent randomization, 709 received the assigned intervention (473 individuals received durvalumab [Imfinzi] and 236 received placebo). As of March 22, 2018, the median follow-up was 25.2 months. The 24-month overall survival rate was 66.3% (95% CI, 61.7–70.4) in the durvalumab (Imfinzi) group, as compared with 55.6% (95% CI, 48.9–61.8) in the placebo group (two-sided P=0.005). Durvalumab (Imfinzi) significantly prolonged OS, as compared with placebo (stratified HR for death, 0.68; 99.73% CI, 0.47–0.997; P=0.0025). Updated analyses regarding PFS were similar to those previously reported, with a median duration of 17.2 months in the durvalumab (Imfinzi) group and 5.6 months in the placebo group (stratified HR for disease progression or death, 0.51; 95% CI, 0.41–0.63). The median time to death or distant metastasis was 28.3 months in the durvalumab (Imfinzi) group and 16.2 months in the placebo group (stratified hazard ratio, 0.53; 95% CI, 0.41–0.68). Consolidation therapy with durvalumab (Imfinzi) resulted in significantly prolonged median OS, PFS, and a greater ORR compared with placebo in a study in individuals with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy.

SMALL CELL LUNG CARCINOMA (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 of durvalumab (Imfinzi) in combination with etoposide and either carboplatin or cisplatin in previously untreated ES-SCLC was investigated in CASPIAN, a randomized, multicenter, active-controlled, phase 3, open-label trial (NCT03043872). The study population characteristics were median age of 63 years (range, 28–82); 65% ECOG PS of 1; and 93% were former/current smokers. Ninety percent of individuals had stage IV disease and 10% had brain metastasis at baseline. A total of 25% of the individuals received cisplatin and 74% of the individuals received carboplatin. In the chemotherapy-alone arm, 57% of the individuals received six cycles of chemotherapy, and 8% of the individuals received prophylactic cranial irradiation.

The evaluation was based on the comparison of individuals randomly assigned to durvalumab (Imfinzi) plus chemotherapy versus chemotherapy alone. The major efficacy outcome measure was OS. Additional efficacy outcome measures were investigator-assessed PFS and ORR per RECIST 1.1. Median OS was 13.0 months (95% CI, 11.5–14.8) in the durvalumab (Imfinzi) plus chemotherapy arm compared with 10.3 months (95% CI, 9.3–11.2) in the chemotherapy-alone arm (HR 0.73; 95% CI, 0.59–0.91; ​P=0.0047). The study demonstrated first-line durvalumab (Imfinzi) plus platinum-etoposide significantly improved OS in participants with ES-SCLC versus a clinically relevant control group.

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

American Hospital Formulary Service (AHFS). Durvalumab (Imfinzi®). AHFS Drug Information 2021. [LexiComp Web site]. 02/26/2021. Available at: https://online.lexi.com/lco/action/home# [via subscription only]. Accessed June 23, 2023.


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: April 06, 2023. Available at: https://clinicaltrials.gov/ct2/show/NCT02125461?term=NCT02125461&draw=2&rank=1. Accessed June 23, 2023.

ClinicalTrials.gov. Durvalumab +/- tremelimumab in combination with platinum based chemotherapy in untreated extensive-stage small cell lung cancer. ClinicalTrials.gov Identifier: NCT03043872. First Posted: February 6, 2017. Last Update Posted: April 21, 2023. Available at: https://clinicaltrials.gov/ct2/show/NCT03043872?term=NCT03043872&draw=2&rank=1. Accessed June 23, 2023.


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: June 22, 2023. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03875235?term=NCT03875235&draw=2&rank=1. Accessed June 23, 2023.


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: June 18, 2023. Available at:  https://www.clinicaltrials.gov/ct2/show/NCT03298451 Accessed June 23, 2023.


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: June 15, 2023. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03164616?term=NCT03164616&draw=2&rank=1. Accessed June 23, 2023.


ClinicalTrials.gov. Study of Durvalumab With Chemoradiotherapy for Women With Locally Advanced Cervical Cancer (CALLA) (CALLA). ClinicalTrials.gov Identifier: NCT03830866. First Posted February 05, 2019. Last Update Posted: April 19, 2023. Available at: https://classic.clinicaltrials.gov/ct2/show/NCT03830866?term=imfinzi&cond=cervical+cancer&draw=2&rank=2. Accessed June 23, 2023.


Durvalumab (Imfinzi®) Package Insert. Wilmington, DE : AstraZeneca Pharmaceuticals LP. 09/2021. Available at: https://www.imfinzi.com/. Accessed June 23, 2023.

Elsevier's Clinical Pharmacology Compendium. Durvalumab (Imfinzi®). [Clinical Key Web site]. 07/29/2021. Available at: https://www.elsevier.com/solutions/clinical-pharmacology. [via subscription only]. Accessed June 23, 2023.

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.

IBM Micromedex® DRUGDEX® (electronic version). Durvalumab (Imfinzi®). [Micromedex Web site]. IBM Watson Health, Greenwood Village, Colorado, USA. 08/12/2021. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed June 23, 2023.


IBM Micromedex® DRUGDEX® (electronic version). Tremelimumab-actl. [Micromedex Web site]. IBM Watson Health, Greenwood Village, Colorado, USA. 08/12/2021. Available at: https://www.micromedexsolutions.com/micromedex2/librarian/CS/2D993D/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSYNC/4114EE/ND_PG/evidencexpert/ND_B/evidencexpert/ND_AppProduct/evidencexpert/ND_T/evidencexpert/PFActionId/evidencexpert.DoIntegratedSearch?SearchTerm=tremelimumab# [via subscription only]. Accessed July 07, 2023.

Lexi-Drugs Compendium. Durvalumab (Imfinzi®). [Lexicomp Web site]. 08/17/2021. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed June 23, 2023.


National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology®-Ampullary Adenocarcinoma. V1.2023 [NCCN] 04/27/2023. Available from: https://www.nccn.org/professionals/physician_gls/pdf/ampullary.pdf. Accessed July 07, 2023.


National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® -Biliary Tract Cancers. V2.2023 [NCCN Web site]. 05/10/2023. Available from: https://www.nccn.org/professionals/physician_gls/pdf/btc.pdf. Accessed July 07, 2023.


National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® –Cervical Cancer.V12023.[NCCN Web site]. 04/28/2023. Available from: https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf. Accessed June 23, 2023.
  
National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® –Hepatobiliary Cancers. V3.2022. [NCCN Web site]. 10/14/2022. Available from: https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf. [via subscription only]. Accessed June 23, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® – Non-small cell lung cancer. V3.2023. [NCCN Web site]. 04/13/2023. Available from: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. [via subscription only]. Accessed June 23, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® – Small cell lung cancer. V3.2023 [NCCN Web site]. 12/21/2022. Available from: https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. [via subscription only]. Accessed June 23, 2023.

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 June 23, 2023.

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 July 07, 2023.

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):649-55.

Ouwens M, Darilay A, Zhang Y, et al. Assessing the influence of subsequent immunotherapy on overall survival in patients with unresectable stage III non-small cell lung cancer from the PACIFIC study. Curr Ther Res Clin Exp. 2021;95:100640.

Paz-Ares L , Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-39.


Tremelimumab-actl (Imjudo®) Package Insert. Wilmington, DE : AstraZeneca Pharmaceuticals LP. 06/2023. Available at: https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/0102c6fd-de8a-4b43-afa3-2a2c2115d472/0102c6fd-de8a-4b43-afa3-2a2c2115d472_viewable_rendition__v.pdf. Accessed July 07, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Durvalumab (Imfinzi®) Prescribing Information. [FDA Web site]. 06/16/2023. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed June 23, 2023.


US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Tremelimumab-actl (Imjudo®) Prescribing Information. [FDA Web site]. [FDA Web site]. 11/10/2022. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761270 . Accessed July 07, 2023.


US Food and Drug Administration (FDA). FDA approves durvalumab for locally advanced or metastatic biliary tract cancer. [FDA Web site]. 09/02/2022. Available at:  https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-locally-advanced-or-metastatic-biliary-tract-cancer?utm_medium=email&utm_source=govdelivery. Accessed June 23, 2023.


US Food and Drug Administration (FDA). FDA approves tremelimumab in combination with durvalumab and platinum-based chemotherapy for metastatic non-small cell lung cancer. [FDA Web site].11/10/2022. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tremelimumab-combination-durvalumab-and-platinum-based-chemotherapy-metastatic-non. Accessed July 10, 2023.

 

US Food and Drug Administration (FDA). FDA approves tremelimumab in combination with durvalumab for unresectable hepatocellular carcinoma. [FDA Web site]. 10/21/2022. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tremelimumab-combination-durvalumab-unresectable-hepatocellular-carcinoma. Accessed July 10, 2023.

 

Van Coillie S, Wiernicki B, Xu J. Molecular and Cellular Functions of CTLA-4. Adv Exp Med Biol. 2020;1248:7-32. doi: 10.1007/978-981-15-3266-5_2. PMID: 32185705. Available at: https://pubmed.ncbi.nlm.nih.gov/32185705/. Accessed July 14, 2023.​

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

Revisions From MA08.123c:
09/04/2023

This version of the policy will become effective 09/04/2023.

Tremelimumab-actl (Imjudo®)​ has been added to the policy name.

​The following policy criteria have been added in accordance with NCCN compendium: 
  • Ampullary Adenocarcinoma (V1.2023; 04/27/2023)
  • Cervical Cancer (V1.2023; 04/28/2023)

The following policy criteria have been added in accordance with Micromedex: Malignant mesothelioma of pleura


The following policy criteria have been revised in accordance with NCCN compendium:

  • Biliary Tract Cancers (V2.2023; 05/10/2023)
  • Non-Small Cell Lung Cancer (V3.2023; 04/13/2023)​

The following ICD-10 CM codes have been added to this policy:
C24.1 Malignant neoplasmof ampulla of Vater
C45.0 Mesothelioma of pleura
C53.1 Malignant neoplasm of exocervix
C53.8 Malignant neoplasm of overlapping sites of cervix uteri
C53.9 Malignant neoplasm of cervix uteri, unspecified
D06.0 Carcinoma in situ of endocervix
D06.1 Carcinoma in situ of exocervix
D06.7 Carcinoma in situ of other parts of cervix
D06.9 Carcinoma in situ of cervix, unspecified


The following HCPCS code has been added to this policy:

J9347 Injection, tremelimumab-actl, 1 mg​


Revisions From MA08.123b:
01/02/2023

This version of the policy will become effective 01/02/2023. 
This policy has been updated in consideration of revisions within the US Food and Drug Administration (FDA) labeling:

    1. Coverage was added for the condition of non-small cell lung cancer.
    2. Coverage was added for the condition of hepatocellular carcinoma.

The following policy criteria have been revised in accordance with NCCN compendium: 
Hepatobiliary Cancers (V3.2022; 10/14/2022​


The following ICD-10 CM codes have been added to this policy:
C22.0  Liver cell carcinoma
C22.1  Intrahepatic bile duct carcinoma
C22.7  Other specified carcinomas of liver
C22.8  Malignant neoplasm of liver, primary, unspecified as to type
C22.9  Malignant neoplasm of liver, not specified as primary or secondary
C23     Malignant neoplasm of gallbladder
C24.0  Malignant neoplasm of extrahepatic bile duct
C24.8  Malignant neoplasm of overlapping sites of biliary tract

C24.9  Malignant neoplasm of biliary tract, unspecified


Revisions From MA08.123a:
01/03/2022
​This version of the policy will become effective 01/03/2022. 

The following criteria have been deleted from this policy in accordance with US Food and Drug Administration (FDA) labeling (07/15/2021) and National Comprehensive Cancer Network (NCCN) compendium (accessed 10/15/2021): 
Urothelial carcinoma

The following policy criteria have been revised in accordance with NCCN compendium: ​
Non-small cell lung cancer (V5.2021; 06/15/2021)
Small cell lung cancer (V1.2022; 08/09/2021)

The following ICD-10 codes have been removed from this policy:

C61, C65.1, C65.2, C65.9, C66.1, C66.2, C66.9, C67.0, C67.1, C67.2, C67.3, C67.4, C67.5, C67.6, C67.7, C67.8, C67.9, C68.0, C68.1, C68.8, C68.9


Revisions From MA08.123:
09/14/20​20This version of the policy will become effective 09/14/2020.

New policy number MA08.123 supersedes MA08.010j for durvalumab (Imfinzi™).

The following criteria have been revised in this policy:

  • endothelial ​bladder cancer and primary carcinoma of the urethra in accordance with National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium® 5.2020
The following criteria have been added to this policy:
  • non-small cell carcinoma and small cell carcinoma in accordance with FDA labeling 06/05/2020 and NCCN Drugs and Biologics Compendium® 5.2020.​

The following ICD-10 CM codes have been added to this policy:


C33 Malignant neoplasm of trachea
C34.00 Malignant neoplasm of unspecified main bronchus
C34.01 Malignant neoplasm of right main bronchus
C34.02 Malignant neoplasm of left main bronchus
C34.10 Malignant neoplasm of upper lobe, unspecified bronchus or lung
C34.11 Malignant neoplasm of upper lobe, right bronchus or lung
C34.12 Malignant neoplasm of upper lobe, left bronchus or lung
C34.2 Malignant neoplasm of middle lobe, bronchus or lung
C34.30 Malignant neoplasm of lower lobe, unspecified bronchus or lung
C34.31 Malignant neoplasm of lower lobe, right bronchus or lung
C34.32 Malignant neoplasm of lower lobe, left bronchus or lung
C34.80 Malignant neoplasm of overlapping sites of unspecified bronchus


9/4/2023
9/1/2023
MA08.123
Medical Policy Bulletin
Medicare Advantage
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