Commercial

Medical Policy

Notification

Avelumab (Bavencio®)

Notification Issued Date:

This version of the policy will become effective 09/14/2020.

New policy number 08.01.64 supersedes 08.01.20j for avelumab (Bavencio®) .

The following criteria have been revised in this policy:

Merkel cell carcinoma; urothelial carcinoma of the urethra, prostate, upper genitourinary tract, and bladder in accordance with National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium® 5.2020

The following criteria have been added to this policy:

Indication of renal cell carcinoma in accordance with FDA labeling 05/14/2019 and NCCN Drugs and Biologics Compendium®.

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

C64.1 Malignant neoplasm of right kidney, except renal pelvis
C64.2 Malignant neoplasm of left kidney, except renal pelvis
C64.9 Malignant neoplasm of unspecified kidney, except renal pelvis

Title:

Avelumab (Bavencio®)

Policy #:

08.01.64d

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.

MEDICALLY NECESSARY

GESTATIONAL TROPHOBLASTIC NEOPLASIA

Avelumab (Bavencio®) is considered medically necessary and, therefore, covered for adult individuals as a single agent for multiagent chemotherapy-resistant disease in either of the following:

High-risk disease
Recurrent or progressive intermediate trophoblastic tumor (placental site trophoblastic tumor or epithelioid trophoblastic tumor)

MERKEL CELL CARCINOMA (MCC)
Avelumab (Bavencio) is considered medically necessary and, therefore, covered in adult and pediatric individuals 12 years and older with MCC as single-agent therapy:

Metastatic (M1 disseminated disease) (National Comprehensive Cancer Network [NCCN] preferred regimen)
Primary clinical N0 locally advanced disease if curative surgery and curative radiation therapy (RT) are not feasible (preferred) or for progression on neoadjuvant nivolumab (Opdivo)
Recurrent N+ regional disease or N0 locally advanced disease if curative surgery and curative RT are not feasible

RENAL CELL CARCINOMA (RCC)
Avelumab (Bavencio) in combination with axitinib (Inlyta) is considered medically necessary and, therefore, covered for adult individuals with advanced RCC as first-line therapy for relapse or stage IV disease and clear cell histology.

UROTHELIAL CARCINOMA (UC)
Avelumab (Bavencio) is considered medically necessary and, therefore, covered as single-agent therapy for the treatment of adult individuals for one of the following indications:

Locally advanced or metastatic UC in individuals with disease progression, in one of the following scenarios:
- During or post–platinum-containing chemotherapy
- Within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
Locally advanced or metastatic UC as single-agent maintenance therapy if there is no progression on first-line platinum-containing chemotherapy that consisted of any of the following regimens:

Gemcitabine and cisplatin
Gemcitabine and carboplatin
DDMVAC (dose-dense methotrexate, vinblastine, doxorubicin, cisplatin)

Recurrent or metastatic primary carcinoma of the urethra that is not recurrent stage T3-4 disease and is without palpable inguinal lymph nodes, as a single-agent, second-line systemic therapy, post-platinum or other chemotherapy (NCCN alternative preferred)
Metastatic UC of the prostate or metastatic upper genitourinary tract (GU) tumors, as a single-agent, second-line systemic therapy, post-platinum or other chemotherapy (NCCN alternative preferred),
Locally advanced or metastatic bladder cancer, as a single-agent (NCCN preferred), second-line systemic therapy, post-platinum or other chemotherapy, in any of the following clinical stages:
- Stage II (cT2, N0) disease or stage IIIA (cT3, N0; cT4a, N0; cT1-T4a, N1) disease if tumor is present following reassessment of tumor status 2 to 3 months after primary treatment with concurrent bladder-preserving chemoradiotherapy and maximal transurethral resection of bladder tumor (TURBT)
- Stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with downstaging systemic therapy or concurrent chemoradiotherapy
- Stage IVA (cT4b, any N, M0) disease if tumor is present following reassessment of tumor status after primary treatment with first-line systemic therapy or concurrent chemoradiotherapy
- 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
- Metastatic stage IVB (any T, any N, M1b) disease
- Muscle invasive local recurrence or persistent disease in a preserved bladder treated with curative intent
- Metastatic or local recurrence postcystectomy treated with curative intent

UTERINE NEOPLASMS
Avelumab (Bavencio) is considered medically necessary and, therefore, covered for adult individuals with endometrial carcinoma (i.e., serous carcinoma, clear cell carcinoma, carcinosarcoma, endometrioid adenocarcinoma, undifferentiated/dedifferentiated carcinoma histology types), as a single-agent second-line or subsequent treatment for recurrent, or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors in one of the following:

Isolated metastases
Disseminated metastases with or without sequential palliative external beam radiation therapy (EBRT)
With sequential EBRT and with or without brachytherapy for locoregional recurrence in individuals with no prior RT to site of recurrence, or previous vaginal brachytherapy only
After surgical exploration, with sequential EBRT for locoregional recurrence in individuals with disease confined to the vagina or paravaginal soft tissue, or in pelvic, para-aortic or common iliac lymph nodes
After surgical exploration, with or without sequential EBRT for locoregional recurrence in individuals with upper abdominal or peritoneal disease
With or without sequential palliative EBRT or brachytherapy for locoregional recurrence in individuals who have received prior EBRT to site of recurrence

THYMOMAS AND THYMIC CARCINOMAS
Avelumab (Bavencio) is considered medically necessary and, therefore, covered for adult individuals with thymic carcinoma after R1 or R2 resection for postoperative systemic therapy in combination with axitinib (Inlyta) for those who cannot tolerate first-line combination regimens.

First-line systemic therapy in combination with axitinib (Inlyta) for recurrent, advanced, or metastatic disease (for thymic carcinomas only) for individuals who cannot tolerate first-line combination regimens for one of the following:

Potentially resectable locally advanced disease
Potentially resectable solitary metastasis or ipsilateral pleural metastasis
Consideration following surgery for solitary metastasis or ipsilateral pleural metastasis
Medically inoperable/unresectable solitary metastasis or ipsilateral pleural metastasis
Extrathoracic metastatic disease

Second-line systemic therapy (for thymic carcinomas only) in combination with axitinib (Inlyta) for one of the following:

Unresectable locally advanced disease
Solitary metastasis or ipsilateral pleural metastasis
Extrathoracic metastatic disease

EXPERIMENTAL/INVESTIGATIONAL

All other uses for avelumab (Bavencio) 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.

MANDATES

PENNSYLVANIA MEMBERS
In accordance with the Commonwealth of Pennsylvania's Act 6 of 2020 or Fair Access to Cancer Treatment Act, for members who are enrolled in Pennsylvania commercial products who have Stage 4, advanced metastatic cancer, refer to the Medical Policy titled "Coverage of Anticancer Prescription Oral and Injectable Drugs and Biologics and Supportive Agents” (08.01.08) for additional information regarding the applicable coverage of 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 benefit contract, avelumab (Bavencio) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

THE EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS

The 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 the 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 (e.g., 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

Avelumab (Bavencio) was approved by the FDA on March 23, 2017, for the treatment of adult and pediatric individuals ages 12 years and older with metastatic Merkel cell carcinoma. Supplemental approvals for avelumab (Bavencio) have since been issued by the FDA.

Avelumab (Bavencio) is administered as an intravenous infusion over 60 minutes.

PEDIATRIC USE
The safety and effectiveness of avelumab (Bavencio) have not been established in pediatric individuals for indications other than metastatic Merkel cell carcinoma.

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. Avelumab (Bavencio) is a PD-L1 blocker. The drug acts by stopping the ligands from attaching to the PD-1 receptor and thus allowing the T cells to recognize the tumor and attack it.

MERKEL CELL CARCINOMA

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with an incidence of approximately 1500 cases per year in the United States, with 12 percent of these cases presenting at stage 4. MCC has a high mortality rate, with a 5-year survival of only 30 percent to 64 percent. Common sites of metastasis are the lymph nodes and distant skin sites.

On March 23, 2017, the US Food and Drug Administration (FDA) granted approval for

avelumab (Bavencio) for the treatment of adult and pediatric individuals 12 years and older with metastatic MCC. The safety and efficacy of

avelumab (Bavencio) was demonstrated in the JAVELIN Merkel 200 trial (NCT02155647), a phase 2, open-label, single-arm, multicenter study conducted in individuals with histologically confirmed metastatic MCC whose disease had progressed on or after chemotherapy administered for distant metastatic disease. The trial excluded individuals with autoimmune disease; medical conditions requiring systemic immunosuppression; prior organ or allogeneic stem cell transplantation; prior treatment with anti-PD-1, anti-PD-L1, or

anticytotoxic T lymphocyte–associated antigen-4 (CTLA-4) antibodies; central nervous system (CNS) metastases; infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; or Eastern Cooperative Oncology Group (ECOG) performance score (PS) greater than 1.

Study participants received

avelumab (Bavencio), 10 mg/kg, as an intravenous (IV) infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. Individuals with radiological disease progression not associated with significant clinical deterioration, defined as no new or worsening symptoms, no change in performance status for greater than 2 weeks, and no need for salvage therapy, could continue treatment. Tumor response assessments were performed every 6 weeks. The major efficacy outcome measures were confirmed overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by a blinded independent central review (BICR) and BICR-assessed duration of response (DOR). RECIST provides a standardized set of rules for response assessment using tumor shrinkage, based on imaging modalities that are globally available and interpretable by most clinicians. This standardization, and the rules and criteria established, provide a framework for reproducible analysis and reporting of changes in tumor size. The reproducibility of these criteria and the correlations with historical trial results serve an important purpose in drug discovery. The efficacy analysis was conducted when the last individual enrolled had completed 12 months of follow-up.

A total of 88 individuals were enrolled. Baseline characteristics were a median age of 73 years (range, 33–88), and the PS was 0 (56 percent) or 1 (44 percent). Seventy-five percent of individuals were 65 years or older, 35 percent were 75 or older, and three percent were 85 or older. Sixty-five percent of individuals were reported to have had one prior anticancer therapy for metastatic MCC and 35 percent had two or more prior therapies. Fifty-three percent of individuals had visceral metastases. All individuals had tumor samples evaluated for PD-L1 expression; of these, 66 percent were PD-L1–positive (≥1 percent of tumor cells), 18 percent were PD-L1 negative, and 16 percent had

nonevaluable results by an investigational immunohistochemistry assay. Archival tumor samples were evaluated for Merkel cell polyomavirus (MCV) using an investigational assay; of the 77 individuals with evaluable results, 52 percent had evidence of MCV.

The study showed an ORR of 33 percent (95 percent confidence interval [CI], 23.3–43.8). Eleven percent of individuals experienced a complete response (95 percent CI, 6.6–19.9), and 22 percent of individuals experienced a partial response (95 percent CI, 13.5–31.7). Tumor responses were durable, with 86 percent of responses lasting for at least 6 months (n=25). Forty-five percent of responses lasted at least 12 months (n=13). DOR ranged from 2.8 to over 23.3 months.

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

RENAL CELL CARCINOMA

In adults, renal cell carcinoma (RCC) accounts for 80 percent to 95 percent of all primary kidney cancers. When diagnosed, 65 percent of individuals have localized disease confined to the kidney. At 75 percent to 85 percent, the clear cell subtype of RCC accounts for the highest percentage among other subtypes of the disease.

The efficacy and safety of

avelumab (Bavencio) in combination with

axitinib (

Inlyta) was demonstrated in the JAVELIN Renal 101 trial (NCT02684006), a phase 3, randomized, multicenter, open-label study of

avelumab (Bavencio) in combination with

axitinib (

Inlyta) in 886 individuals with untreated advanced RCC regardless of tumor PD-L1 expression (intent-to-treat [ITT] population). Individuals with autoimmune disease or conditions requiring systemic immunosuppression were excluded.

Randomization was stratified according to PS (0 vs 1) and region (United States vs Canada/Western Europe vs the rest of the world). Participants were randomly assigned (1:1) to one of the following treatment arms:

Avelumab (Bavencio), 10 mg/kg IV every 2 weeks in combination with axitinib (Inlyta), 5 mg twice daily orally (N=442). Individuals who tolerated axitinib (Inlyta) 5 mg twice daily without grade 2 or greater axitinib (Inlyta)-related adverse events for 2 consecutive weeks could increase to 7 mg and then subsequently to 10 mg twice daily. Axitinib (Inlyta) could be interrupted or reduced to 3 mg twice daily and subsequently to 2 mg twice daily to manage toxicity.
Sunitinib, 50 mg once daily orally for 4 weeks followed by 2 weeks off (N=444) until radiographic or clinical progression or unacceptable toxicity

Treatment with

avelumab (Bavencio) and

axitinib continued until RECIST 1.1 defined progression of disease by BICR assessment or unacceptable toxicity. Administration of

avelumab (Bavencio) and

axitinib was permitted beyond RECIST-defined disease progression if the individual was clinically stable and considered to be deriving clinical benefit by the investigator. Assessment of tumor status was performed at baseline, after randomization at 6 weeks, then every 6 weeks thereafter up to 18 months after randomization, and every 12 weeks thereafter until documented confirmed disease progression by BICR.

Baseline characteristics were a median age of 61 years (range, 27–88), 38 percent of individuals were 65 years or older, and the PS was 0 (63 percent) or 1 (37 percent), respectively. Individual distribution by International Metastatic Renal Cell Carcinoma Database (IMDC) risk groups was 21 percent favorable, 62 percent intermediate, and 16 percent poor.

The major efficacy outcome measures were progression-free survival (PFS), as assessed by a BICR using RECIST 1.1 and overall survival (OS) in individuals with PD-L1–positive tumors using a clinical trial assay (PD-L1 expression level one percent or greater). Because PFS was statistically significant in individuals with PD-L1–positive tumors (HR, 0.61 [95 percent CI, 0.48–0.79]), it was then tested in the ITT population and a statistically significant improvement in PFS in the ITT population was also demonstrated.

Among individuals with previously untreated advanced RCC, treatment with

avelumab (Bavencio) plus

axitinib continued to result in a statistically significant improvement in PFS versus

sunitinib (

Sutent). The final analysis for OS was not statistically significant for either the PD-L1–positive or ITT population.

UROTHELIAL CARCINOMA

The urinary tract comprises the renal pelvis, ureters, bladder, and urethra. The innermost lining of the urinary tract is composed of urothelial cells. Urothelial carcinoma (UC), also known as transitional cell carcinoma (TCC), is the ninth most common cancer overall worldwide, accounting for 90 percent of all bladder cancers. Squamous cell carcinoma comprises 1 percent to 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 9, 2017,

avelumab (Bavencio) was approved by the FDA for the treatment of individuals with locally advanced or metastatic UC 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 and safety of

avelumab (Bavencio) was demonstrated in the UC cohorts of the JAVELIN Solid Tumor trial (NCT01772004), an open-label, single-arm, multicenter study that included 242 individuals with locally advanced or metastatic UC with disease progression on or after platinum-containing chemotherapy or who had disease progression within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant chemotherapy regimen. Individuals with active or history of CNS metastasis; other malignancies within the last 5 years; organ transplant; conditions requiring therapeutic immune suppression; or active infection with HIV, hepatitis B, or hepatitis C were excluded. Individuals with autoimmune disease, other than type 1 diabetes, vitiligo, psoriasis, or thyroid disease that did not require immunosuppressive treatment, were excluded. Individuals were included regardless of their PD-L1 status.

Study participants received

avelumab (Bavencio) at a dose of 10 mg/kg IV every 2 weeks until radiographic or clinical progression or unacceptable toxicity. Tumor response assessments were performed every 6 weeks. Efficacy outcome measures included confirmed ORR as assessed by a BICR using RECIST 1.1 and DOR. Efficacy was evaluated in individuals who were followed for a minimum of both 13 weeks and 6 months at the time of data cut-off.

Baseline demographic and disease characteristics for the 226 individuals with a minimum of 13 weeks of follow-up were median age 68 years (range, 30–89), and 66 percent of individuals had a PS 0 or 1. Forty-four percent of individuals had nonbladder UC including 23 percent of individuals with upper tract disease, and 83 percent of individuals had visceral metastases (baseline target and/or

nontarget lesions present outside of the lymph nodes). Nine individuals (4 percent) had disease progression following prior platinum-containing neoadjuvant or adjuvant therapy only. Forty-seven percent of individuals only received prior cisplatin-based regimens, 32 percent received only prior carboplatin-based regimens, and 20 percent received both cisplatin and carboplatin-based regimens. At baseline, 17 percent of individuals had a hemoglobin less than 10 g/

dL and 34 percent of individuals had liver metastases.

The median time to response was 2.0 months (range,1.3–11.0) among individuals followed up for greater than 13 weeks or greater than 6 months. Using a clinical trial assay to assess PD-L1 staining, with 16 percent of individuals not evaluable, there were no clear differences in response rates based on PD-L1 tumor expression. Among the total 30 responding individuals followed for greater than 13 weeks, 22 individuals (73 percent) had an ongoing response of 6 months or longer and four individuals (13 percent) had ongoing responses of 12 months or longer. Among the total 26 responding individuals followed for greater than 6 months, 22 individuals (85 percent) had ongoing responses of 6 months or longer and four individuals (15 percent) had ongoing responses of 12 months or longer.

OFF-LABEL INDICATIONS

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 Cancer Society. Bladder cancer. [American Cancer Society Web site]. Available at: https://www.cancer.org/cancer/types/bladder-cancer.html. Accessed November 16, 2023.

American Hospital Formulary Service (AHFS). Avelumab (Bavencio^®). AHFS Drug Information 2023. [Lexicomp Web site]. 04/21/2023. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed November 16, 2023.

Avelumab (Bavencio^®). Package insert. Rockland, MA: EMD Serono, Inc. 09/2023. Available at: https://www.bavencio.com/hcp. Accessed November 16, 2023.

Bellmunt J. Treatment of metastatic urothelial cancer of the bladder and urinary tract. [UpToDate Web site]. 10/26/2023. Available at: https://www.uptodate.com/contents/treatment-of-metastatic-urothelial-cancer-of-the-1bladder-and-urinary-tract [via subscription only]. Accessed November 16, 2023.

ClinicalTrials.gov. A study of avelumab in patients with locally advanced or metastatic urothelial cancer (JAVELIN Bladder 100). ClinicalTrials.gov Identifier: NCT02603432. First Posted: November 11, 2015. Last Update Posted: June 6, 2023. Available at: https://clinicaltrials.gov/. Accessed November 16, 2023.

ClinicalTrials.gov. A study of avelumab with axitinib versus sunitinib in advanced renal cell carcinoma (JAVELIN Renal 101). ClinicalTrials.gov Identifier: NCT02684006. First Posted: February 17, 2016. Last Update Posted November 9, 2023. Available at: https://clinicaltrials.gov/. Accessed November 16, 2023.

ClinicalTrials.gov. Avelumab in chemo-resistant gestational trophoblastic neoplasias (TROPHIMMUN). ClinicalTrials.gov Identifier: NCT03135769. First Posted: May 1, 2017. Last Update Posted: September 2, 2021. Available at: https://clinicaltrials.gov/. Accessed November 16, 2023.

ClinicalTrials.gov. Avelumab in metastatic or locally advanced solid tumors (JAVELIN Solid Tumor). ClinicalTrials.gov Identifier: NCT01772004. First Posted: January 21, 2013. Last Update Posted: December 20, 2021. Available at: https://clinicaltrials.gov/. Accessed November 16, 2023.

ClinicalTrials.gov. Avelumab in participants with Merkel cell carcinoma (JAVELIN Merkel 200). ClinicalTrials.gov Identifier: NCT02155647. First Posted: June 4, 2014. Last Update Posted: June 5, 2023. Available at: https://clinicaltrials.gov/. Accessed November 16, 2023.

D’Angelo SP, Bhatia S, Brohl AS, et al. Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial. J Immunother Cancer. 2020;8(1):e000674.

D’Angelo SP, Lebbe C, Mortier L, et al. First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): primary and biomarker analyses of a phase II study. J Immunother Cancer. 2021;9(7):e002646.

Elsevier Clinical Pharmacology Compendium. Avelumab (Bavencio^®). [MD Consult Web site]. 12/30/2020. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed November 16, 2023.

Konstantinopoulos PA, Luo W, Liu JF, et al. Phase II study of avelumab in patients with mismatch repair deficient and mismatch repair proficient recurrent/persistent endometrial cancer. J Clin Oncol. 2019;37(30)2786-2794.

Lexi-Drugs Compendium. Avelumab (Bavencio^®). [Lexicomp Web site]. 09/20/2023. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed November 16, 2023.

Merative Micromedex^® DRUGDEX^® (electronic version). Avelumab (Bavencio^®). [Micromedex Web site]. Merative L.P., Ann Arbor, Michigan, USA. 09/14/2023. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed November 16, 2023.

Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1103-1115.

National Cancer Institute (NCI). Endometrial cancer treatment. [Cancer.gov Web site]. 03/13/2023. Available at: https://www.cancer.gov/types/uterine/hp/endometrial-treatment-pdq. Accessed November 16, 2023.

National Cancer Institute (NCI). Gestational trophoblastic disease treatment. [Cancer.gov Web site]. 10/20/2022. Available at: https://www.cancer.gov/types/gestational-trophoblastic/hp/gtd-treatment-pdq. Accessed November 16, 2023.

National Cancer Institute (NCI). NCI dictionary of cancer terms. RECIST. [Cancer.gov Web site]. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/recist#:~:text=A standard way to measure,CT scans, or MRI scans. Accessed November 16, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Bladder cancer. v5.2024; 10/28/2024. Available at: https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf [via free subscription only]. Accessed November 01, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Gestational Trophoblastic Neoplasia. v2.2024; 08/19/2024. Available at: https://www.nccn.org/professionals/physician_gls/pdf/gtn.pdf. [via free subscription only]. Accessed November 01, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Kidney Cancer. v2.2025; 09/06/2024. Available at:
https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf [via free subscription only]. Accessed November 01, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Merkel Cell Carcinoma. v1.2024; 11/22/2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/mcc.pdf [via free subscription]. Accessed November 01, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Uterine Neoplasms. v3.2024; 09/20/2024. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf [via free subscription only]. Accessed November 01, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Thymomas and thymic cancer. v1.2025; 10/30/2024. Available at: https://www.nccn.org/professionals/physician_gls/pdf/thymomas.pdf [via free subscription only]. Accessed November 01, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium^®. Avelumab (Bavencio^®). [NCCN Web site]. Available at: https://www.nccn.org/professionals/drug_compendium/content/. Accessed November 01, 2024.

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.

Powles T, Park SH, Voog E, et al. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N Engl J Med. 2020;383(13):1218-1230.

Sachdeva K. Renal cell carcinoma. [Medscape Web site]. 03/21/2023. Available at: https://emedicine.medscape.com/article/281340-overview#showall. Accessed November 16, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Avelumab (Bavencio^®) Prescribing information. [FDA Web site]. 09/06/2023. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed November 16, 2023.

You B, Bolze PA, Lotz JP, et al. Avelumab in patients with gestational trophoblastic tumors with resistance to single-agent chemotherapy: cohort A of the TROPHIMMUN phase II trial. J Clin Oncol. 2020;38:3129-3137.

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)

J9023 Injection, avelumab, 10 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From 08.01.64d:

01/06/2025

This version of the policy will become effective 01/06/2025.

The following policy criteria have been revised in accordance with National Comprehensive Cancer Network (NCCN) guidelines:

Merkel Cell Carcinoma
Uterine Neoplasms

The following policy criteria have been added in accordance with NCCN guidelines:

Thymomas and Thymic Carcinomas

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

C37 Malignant neoplasm of thymus
C7A.091 Malignant carcinoid tumor of the thymus

Revisions From 08.01.64c

01/02/2024

This version of the policy will become effective 01/02/2024.

The following policy criteria have been revised in accordance with National Comprehensive Cancer Network (NCCN) compendium accessed 09/20/2023 and the corresponding guidelines:

Gestational Trophoblastic Neoplasia (V1.2023; 12/20/2022)
Merkel Cell Carcinoma (V1.2023; 04/10/2023)
Urothelial Carcinoma (Bladder Cancer V3.2023; 05/25/2023)
Uterine Neoplasms (V1.2024; 09/20/2023)

Revisions From 08.01.64b:

12/19/2022

This version of the policy will become effective 12/19/2022.

The following criteria have been revised in this policy in accordance with National Comprehensive Cancer Network (NCCN) guidelines:

Bladder cancer (V2.2022; 05/20/2022)
Gestational trophoblastic neoplasia (V1.2022; 10/06/2021)
Merkel cell carcinoma (V2.2022; 03/24/2022)
Uterine neoplasms (V1.2022; 11/04/2021)

The following ICD-10 codes have been added to this policy:
D09.0 Carcinoma in situ of bladder
D39.2 Neoplasm of uncertain behavior of placenta
O01.0 Hydatidiform mole, unspecified

The following ICD-10 codes have been removed from this policy:
C4A.10 Merkel cell carcinoma of unspecified eyelid, including canthus
C4A.20 Merkel cell carcinoma of unspecified ear and external auricular canal
C4A.30 Merkel cell carcinoma of unspecified part of face
C4A.60 Merkel cell carcinoma of unspecified upper limb, including shoulder
C4A.70 Merkel cell carcinoma of unspecified lower limb, including hip
C64.9 Malignant neoplasm of unspecified kidney, except renal pelvis
C65.9 Malignant neoplasm of unspecified renal pelvis
C66.9 Malignant neoplasm of unspecified ureter

Revisions From 08.01.64a:

01/03/2022

This version of the policy will become effective 01/03/2022.

The following criteria have been added to this policy in accordance with National Comprehensive Cancer Network (NCCN) Drugs compendium (accessed 10/15/2021) and NCCN guidelines:

Gestational trophoblastic neoplasia (V2.2021; 03/31/2021)
Uterine neoplasms (V4.2021; 09/03/2021)

The following criteria have been revised in this policy in accordance with FDA labeling (11/10/2020) and NCCN guidelines:

Bladder cancer (V4.2021; 07/20/2021
Kidney cancer (V2.2022; 09/08/2021)
Merkel cell carcinoma (V1.2021; 02/18/2021)

The following has been added to this policy in accordance with the Commonwealth of Pennsylvania:
Act 6 mandate of 2020

The following ICD-10 CM codes have been added to this policy:
C54.0, C54.1, C54.2, C54.3, C54.8, C54.9, C55, C58

Revisions From 08.01.64:

09/14/2020

This version of the policy will become effective 09/14/2020.

New policy number 08.01.64 supersedes 08.01.20j for avelumab (Bavencio®) .

The following criteria have been revised in this policy:

Merkel cell carcinoma; urothelial carcinoma of the urethra, prostate, upper genitourinary tract, and bladder in accordance with National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium® 5.2020

The following criteria have been added to this policy:

Indication of renal cell carcinoma in accordance with FDA labeling 05/14/2019 and NCCN Drugs and Biologics Compendium®.

Version Effective Date:

1/6/2025

Version Issued Date:

12/30/2024

Version Reissued Date: