Medicare Advantage

Durvalumab (Imfinzi™)
MA08.123

Policy


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



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.

MEDICALLY NECESSARY

UROTHELIAL CARCINOMA
Durvalumab (Imfinzi™) is considered medically necessary and, therefore, covered as single-agent therapy for the treatment of one of the following indications:
  • Locally advanced or metastatic urothelial carcinoma in individuals who have disease progression in one of the following scenarios:
    • During or following platinum-containing chemotherapy
    • Within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
  • As second-line systemic therapy post-platinum (National Comprehensive Cancer Network [NCCN] alternative preferred regimen) for bladder cancer in any of the following clinical stages:
    • Stage IIIB (T1-T4a, N2,3) disease following partial response or progression after primary treatment with downstaging systemic therapy or concurrent chemoradiotherapy
    • Stage IVA (T4b, any N, M0) disease if tumor is present following reassessment of tumor status after primary treatment with first-line systemic therapy or concurrent chemoradiotherapy
    • 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
    • Stage IVB (any T, any N, M1b) disease
    • Muscle invasive local recurrence or persistent disease in a preserved bladder
    • Metastatic or local recurrence post cystectomy
  • As second-line systemic therapy post-platinum (NCCN alternative preferred regimen) for metastatic disease for one of the following conditions:
    • Primary carcinoma of the urethra that is not recurrent stage T3-T4 disease and is without palpable inguinal lymph nodes
    • Upper genitourinary tract tumors
    • Urothelial carcinoma of the prostate

NON-SMALL CELL LUNG CARCINOMA
Durvalumab (Imfinzi™) is considered medically necessary and, therefore, covered for the treatment of individuals with non-small cell lung cancer (NSCLC) when all of the following criteria are met:
  • As consolidation therapy (i.e., a shorter and more intense treatment phase to further reduce the number of cancer cells; also called intensification therapy and postremission therapy).
  • Disease is unresectable stage III without progression after two or more cycles of concurrent platinum-based chemotherapy and radiation therapy.
  • The individual has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

SMALL CELL LUNG CARCINOMA
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) 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

EXPERIMENTAL/INVESTIGATIONAL

All other uses for durvalumab (Imfinzi™) 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):649-655.

TNM STAGING SYSTEM

According to the American Joint Committee on Cancer (AJCC), the TNM system is based on 3 key pieces of information:
  • T describes how far the main (primary) tumor has grown through the bladder wall and whether it has grown into nearby tissues.
  • N indicates any cancer spread to lymph nodes near the bladder. Lymph nodes are bean-sized collections of immune system cells, to which cancers often spread first.
  • M indicates whether or not the cancer has spread (metastasized) to distant sites, such as other organs or lymph nodes that are not near the bladder.

Numbers or letters appear after T, N, and M to provide more details about each of these factors. Higher numbers mean the cancer is more advanced.

American Cancer Society. Bladder cancer stages. Last Revised: 05/23/2016.

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.

PEDIATRIC USE

The safety and effectiveness of durvalumab (Imfinzi™) 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 won't attack the tumor; thus, the tumor can continue to proliferate.

Durvalumab (Imfinzi™) is a human monoclonal antibodies 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.

DURVALUMAB (IMFINZI) INDICATIONS

UROTHELIAL CARCINOMA
The urinary tract is composed of the the renal pelvis, ureters, bladder, and urethra. The innermost lining of the urinary tract is composed of urothelial cells. Urothelial carcinoma, also known as transitional cell carcinoma (TCC), is the ninth most common cancer overall worldwide and it accounts for 90 percent of all bladder cancers. Squamous cell carcinoma comprises 1-7 percent of upper tract urothelial tumors. Adenocarcinoma accounts for less than 1 percent of upper tract tumors. Urothelial tumors of the renal pelvis and ureters are rare. Tumors of the renal pelvis account for approximately 5 percent of all urothelial tumors of the urinary tract.

On May 1, 2017, the US FDA granted approval for durvalumab (Imfinzi™) for the treatment of individuals with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

The efficacy of durvalumab (Imfinzi™) was evaluated in the urothelial carcinoma cohort of Study 1108 (NCT01693562), a multicenter, multi-cohort, open-label clinical trial. In Study 1108, 182 individuals with locally advanced or metastatic urothelial carcinoma were enrolled. Individuals had progressed while on or after a platinum-based therapy, including those who progressed within 12 months of receiving therapy in a neo-adjuvant or adjuvant setting. These individuals had initiated durvalumab (Imfinzi™) at least 13 weeks prior to the data cut-off date. The trial excluded individuals with a history of immunodeficiency; medical conditions that required systemic immunosuppression (not to exceed 10 mg per day of prednisone or equivalent); history of severe autoimmune disease; untreated CNS metastases; HIV; active tuberculosis, or hepatitis B or C infection. All individuals received durvalumab (Imfinzi™) 10 mg/kg intravenously every 2 weeks for up to 12 months or until unacceptable toxicity or disease progression. Tumor assessments were performed at Weeks 6, 12, and 16, then every 8 weeks for the first year and every 12 weeks thereafter. The major efficacy outcome measures were confirmed Overall Response Rate (ORR) according to RECIST v1.1 as assessed by Blinded Independent Central Review (BICR), and duration of response (DoR).

The median age was 67 years (range: 34 to 88); 66 percent of individuals had visceral metastasis (bone, liver, or lung), including 34 percent with liver metastasis. Lymph node only metastasis were present in 13 percent of individuals. Sixty-six percent of individuals had ECOG performance status of 1, and 41 percent of individuals had a baseline creatinine clearance < 60 mL/min. The Bellmunt risk score (which includes ECOG performance status, baseline hemoglobin, and liver metastases) was 0 in 23 percent, 1 in 38 percent, 2 in 29 percent, and 3 in 9 percent of individuals. Twenty percent of individuals had disease progression following platinum-containing neoadjuvant or adjuvant chemotherapy as their only prior line of therapy. Seventy percent of individuals received prior cisplatin, 30 percent prior carboplatin and 35 percent received ≥ 2 prior lines of systemic therapy.


Tumor specimens were evaluated prospectively for PD-L1 expression on tumor cells (TC) and immune cells (IC) at a central laboratory using the VENTANA PD-L1 (SP263) Assay. Of the 182 individuals, 52 percent were classified as PD-L1 high (if ICs involve > 1 percent of the tumor area, TC ≥ 25 percent or IC ≥ 25 percent; if ICs involve ≤ 1 percent of the tumor area, TC ≥ 25 percent or IC = 100 percent), 40 percent as PD-L1 low/negative (did not meet criterion for PD-L1 high), and samples for 8 percent were not evaluable.


In the urothelial carcinoma cohort of Study 1108, the median follow-up time was 5.6 months. In 37 individuals who had received only neoadjuvant or adjuvant therapy prior to study entry, 24 percent responded. Among the total 31 responding individuals, 45 percent had ongoing responses of 6 months or longer and 16 percent had ongoing responses of 12 months or longer.


Durvalumab demonstrated efficacy in a small open-label trial of individuals with locally advanced or metastatic urothelial carcinoma in which they had progressed while on or after a platinum-based therapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. The safety profile was manageable.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.


NON-SMALL CELL LUNG CARCINOMA
On February 16, 2018, the Food and Drug Administration approved durvalumab (Imfinzi, AstraZeneca Inc.) for patients with unresectable stage III non-small cell lung cancer (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 a ECOG performance status of 0 or 1. The study excluded individuals who had progressed following concurrent chemoradiation, individuals with active or prior documented autoimmune disease within two 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), and smoking history (smoker vs. non-smoker). Individuals were randomized 2:1 to receive durvalumab (Imfinzi™) 10 mg/kg or placebo intravenously every two weeks for up to 12 months or until unacceptable toxicity or confirmed RECIST v1.1-defined progression. Assessment of tumor status was performed every eight weeks. The major efficacy outcome measures were progression-free survival (PFS) as assessed by a BICR RECIST v1.1, and overall survival (OS). Additional efficacy outcome measures included ORR and DoR assessed by BICR.

Of the 713 individuals who underwent randomization, 709 received the assigned intervention (473 individuals received durvalumab 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 percent (95 percent confidence interval [CI], 61.7 to 70.4) in the durvalumab group, as compared with 55.6 percent (95 percent CI, 48.9 to 61.8) in the placebo group (two-sided P=0.005). Durvalumab (Imfinzi™) significantly prolonged overall survival, as compared with placebo (stratified hazard ratio for death, 0.68; 99.73 percent CI, 0.47 to 0.997; P=0.0025). Updated analyses regarding progression-free survival were similar to those previously reported, with a median duration of 17.2 months in the durvalumab group and 5.6 months in the placebo group (stratified hazard ratio for disease progression or death, 0.51; 95 percent CI, 0.41 to 0.63). The median time to death or distant metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo group (stratified hazard ratio, 0.53; 95 percent CI, 0.41 to 0.68).

Consolidation therapy with durvalumab (Imfinzi™) resulted in significantly prolonged median overall survival, progression-free survival, and a greater objective response rate compared with placebo in a study in individuals with stage III non-small cell lung cancer who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy.

SMALL CELL LUNG CARCINOMA
On March 27, 2020, the US 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 to 82); 65 percent ECOG PS of 1; and 93 percent were former/current smokers. Ninety percent of individuals had Stage IV disease and 10 percent had brain metastasis at baseline. A total of 25 percent of the individuals received cisplatin and 74 percent of the individuals received carboplatin. In the chemotherapy alone arm, 57 percent of the individuals received six cycles of chemotherapy, and 8 percent of the individuals received prophylactic cranial irradiation.

The evaluation was based on the comparison of individuals randomized to durvalumab (Imfinzi™) plus chemotherapy vs. chemotherapy alone. The major efficacy outcome measure was overall survival (OS). Additional efficacy outcome measures were investigator-assessed progression-free survival (PFS) and objective response rate (ORR), per RECIST v1.1. Median OS was 13.0 months (95 percent CI: 11.5, 14.8) in the durvalumab (Imfinzi™) plus chemotherapy arm compared with 10.3 months (95 percent CI: 9.3, 11.2) in the chemotherapy alone arm (hazard ratio 0.73; 95 percent CI: 0.59, 0.91; p=0.0047).

The study demonstrated first-line durvalumab plus platinum-etoposide significantly improved overall survival in patients with ES-SCLC versus a clinically relevant control group.



References


Durvalumab (Imfinzi™) . American Hospital Formulary Service (AHFS). Drug Information 2020. [Lexicomp Online Web Site]. 03/04/2020. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed June 25, 2020.

Durvalumab (Imfinzi). Lexi-Drugs Compendium. [Lexicomp Online Web site]. 06/20/2020. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed June 25, 2020.

Durvalumab (Imfinzi). Micromedex Solutions. [Micromedex® Web site]. 06/11/2020. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed June 25, 2020.

Durvalumab (Imfinzi) Package Insert. AstraZeneca Pharmaceuticals LP; Wilmington, DE. May 2020. Available at: https://www.imfinzi.com/. Accessed June 25, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Bladder Cancer.V.5.2020. [NCCN Web site]. 05/12/2020. Available at: https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf . Accessed June 25, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Durvalumab. [NCCN Web site]. June 2020. Available at: https://www.nccn.org/professionals/drug_compendium/content/ [via subscription only]. Accessed June 25, 2020.

National Institutes of Health. Clinical trials: A phase 1/2 study to evaluate the safety, tolerability, and pharmacokinetics of MEDI4736 in subjects with advanced solid tumors (NCT 01693562). [Clinical Trials Web site]. 09/26/2012. (Updated 03/19/2020). Available at: https://clinicaltrials.gov/ct2/show/NCT01693562. Accessed June 25, 2020. 

National Institutes of Health. Clinical trials: A phase III, randomized, multicenter, open-label, comparative study to determine the efficacy of durvalumab or durvalumab and tremelimumab in combination with platinum-based chemotherapy for the first-line treatment in patients with extensive disease small-cell lung cancer (SCLC) (CASPIAN). (NCT03043872). [Clinical Trials Web site]. 02/06/2017. (Updated 03/30/2020). Available at:
https://clinicaltrials.gov/ct2/show/record/NCT03043872 . Accessed June 25, 2020.

National Institutes of Health. Clinical trials: a phase III, randomised, double-blind, placebo-controlled, multi-centre, international study of medi4736 as sequential therapy in patients with locally advanced, unresectable non-small cell lung cancer (stage III) who have not progressed following definitive, platinum-based, concurrent chemoradiation therapy (PACIFIC). (NCT02125461). [Clinical Trials Web site]. 04/29/2014. (Updated 03/19/2020). Available at:
https://clinicaltrials.gov/ct2/show/NCT02125461 . Accessed June 25, 2020.

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):1929-1939.


Powles T, O'Donnell PH, Massard C, et al. Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: updated results from a phase 1/2 open-label study. JAMA Oncol.2017;3(9):e172411.


US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @FDA. Durvalumab (Imfinzi) Prescribing Information. [FDA Website]. 06/05/2020. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed June 25, 2020.



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

Revenue Code Number(s)
N/A



Coding and Billing Requirements


Policy History

9/14/2020
9/14/2020
MA08.123
Medical Policy Bulletin
Medicare Advantage
{"1924": {"Id":1924,"MPAttachmentLetter":"A","Title":"ICD-10 Codes and Narratives","MPPolicyAttachmentInternalSourceId":4686,"PolicyAttachmentPageName":"2c353d16-201e-4684-9657-003c3bef9330"},}
No