Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Enfortumab vedotin-ejfv (Padcev™)

Policy #:08.00.43a



The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, 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. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract. 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

Enfortumab vedotin-ejfv (Padcev™) is considered medically necessary and, therefore, covered for adult individuals with locally advanced or metastatic urothelial cancer (mUC) when all of the following criteria listed below are met:
  • Previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor
  • Previously received a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting
  • Absent of active central nervous system metastases
  • ECOG performance status score of 0-1

CONTINUATION THERAPY

Continuation of treatment with enfortumab vedotin-ejfv (Padcev™) is considered medically necessary and, therefore, covered for adult individuals with locally advanced or metastatic urothelial cancer when both of the following criteria listed below are met:
  • Currently treated with enfortumab vedotin-ejfv and continues to meet initial criteria above
  • Demonstrated continued clinical benefit on enfortumab vedotin-ejfv therapy as defined by tumor response or lack of disease progression, and an acceptable toxicity profile

EXPERIMENTAL/INVESTIGATIONAL

All other uses of enfortumab vedotin-ejfv (Padcev™) 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 benefit contract, enfortumab vedotin-ejfv (Padcev™) for intravenous infusion is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Enfortumab vedotin-ejfv (Padcev™) was approved by the FDA on December 18, 2019 for adult patients in the treatment of locally advanced or metastatic urothelial cancer (mUC) who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting.

DOSING AND FREQUENCY

The recommended dose of Padcev™ is 1.25 mg/kg (up to a maximum of 125 mg for individuals ≥100 kg)
administered as an IV infusion. Padcev™ is given over 30 minutes on days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. The recommended dose reduction schedule is as follows: starting dose is 1.25 mg/kg, up to 125 mg; 1st dose reduction is 1.0 mg/kg, up to 100 mg; 2nd dose reduction is 0.75 mg/kg, up to 75 mg; 3rd dose reduction is 0.5 mg/kg, up to 50 mg.

EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS*

Developed by the Eastern Cooperative Oncology Group, the ECOG Scale of Performance Status is a measurement to assess how disease impacts an individual's daily living abilities. The ECOG Performance Status describes an individual’s level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.). This numbering scale is one way to define the population of participants to be studied in a clinical trial, so that it can be uniformly reproduced among physicians who enroll participants. It is also a way to track changes in a participant’s level of functioning as a result of treatment during a trial.
GRADE
ECOG PERFORMANCE STATUS
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 house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3
Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4
Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
5
Dead

*Oken M, Creech R, Tormey D, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649-655.
Description

Bladder cancer is a common urologic cancer. Approximately 80,000 people in the United States (U.S.) will be diagnosed with bladder cancer annually. Urothelial carcinoma, the most commonly diagnosed epithelial tumor in the U.S., accounts for 90 percent of all bladder cancers and can also be found in the renal pelvis, ureter, and urethra. Urothelial cancers occur more commonly in men than in women (3:1), with a peak incidence in the seventh decade of life. Clinical management of bladder cancer is challenging due to the heterogeneity in bladder tumors with respect to invasion and metastasis and frequent recurrence in the bladder among individuals treated with bladder preservation therapies. Locally advanced bladder cancers are cancers that have grown through the bladder wall or spread only to lymph nodes. Cisplatin-based chemotherapy remains the standard of care for first-line treatment for locally advanced/metastatic urothelial cancer. Current treatment guidelines recommend anti-programmed death 1 or anti-programmed death-ligand 1 (PD-1/L1) therapy in second-line after platinum-based chemotherapy, or as first line therapy in select cisplatin-ineligible individuals.

Enfortumab vedotin-ejfv (Padcev™) is a Nectin-4-directed antibody and microtubule inhibitor conjugate indicated for the treatment for adult individuals with locally advanced or metastatic urothelial cancer (mUC) who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. This indication was approved under accelerated approval based on tumor response rate.

PEER-REVIEWED LITERATURE
Summary

EV-201 was a single-arm, multi-center phase II trial which enrolled 125 participants with la/mUC into 2-cohort study, for individuals who were treated with prior platinum-containing chemotherapy and anti-PD-1/L1 therapy (Cohort 1), or anti-PD-1/L1 therapy and no prior chemotherapy and were cisplatin-ineligible (Cohort 2). The median age was 69 years (range: 40 to 84 years), 70% were male, and 85% were Caucasian. All participants had a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 (32%) or 1 (68%). Ninety percent had visceral metastases including 40% of the participants presenting with liver metastases. Nectin-4 expression was present in all who were tested (n=120). The median number of prior systemic therapies was 3 (range: 1 to 6). 46% of participants received prior PD-1 inhibitor, 42% received prior PD-L1 inhibitor, and an additional 13% received both PD-1 and PD-L1 inhibitors. 66% of participants received prior cisplatin based regimens, 26% received prior carboplatin-based regimens, and an additional 8% received both cisplatin and carboplatin-based regimens.

The primary efficacy outcome measures were confirmed objective response rate (ORR) and duration of response (DOR) assessed by a blinded independent central review (BICR). The researchers report results of 44% ORR (N=125; 95 % CI:35.1%,53.2%), with a median duration of response of 7.6 months, and a maximum duration of 15.6 months. The ORR consisted of confirmed complete response ([CR], 12%) and partial response ([PR], 32%), respectively. CR was defined as the disappearance of all target lesions. PR was defined as a ≥30% decrease in the sum of diameters of target lesions, utilizing the baseline sum diameters as a reference. Treatment continued until disease progression or unacceptable toxicity. The median duration of follow-up was 10.2 months (range, 0.5 to 16.5 months). The study included secondary endpoints: progression-free survival, and overall survival.

Additional studies are warranted to evaluate if the specific etiology of carcinoma characteristics (epithelial, squamous differentiation, or other histological variants) within this extremely comprised population influences objective outcomes (e.g., overall survival, progression-free survival).

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

Hurwitz M, Spiess PE, Garcia JA, et al, Urothelial and Kidney Cancers. June 01, 2016. Cancer Network. Available at: http://www.cancernetwork.com/cancer-management/urothelial-and-kidney-cancers. Accessed on February 21, 2020.


National Cancer Institute. NCI Dictionary of Cancer Terms. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/locally-advanced-cancer. Accessed on February 21, 2020.

National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Bladder Cancer, version 3.2020. Revised January 17, 2020. Available at: https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed on February 21, 2020.

Oken M, Creech R, Tormey D, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649-655.

Richards KA, Jarrard DF. Urothelial Tumors of the Renal Pelvis and Ureters. Jan 15, 2020. Medscape. Available at: http://emedicine.medscape.com/article/452449-overview#a8. Accessed on February 21, 2020.

Rosenberg JE, O’Donnell PH, Balar AV, et al. Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti-programmed death 1/programmed death ligand 1 therapy. J Clin Oncol. 2019;37(29):2592-600.

US Food and Drug Administration. Center for Drug Evaluation and Research. PADCEV™ (enfortumab vedotin-ejfv). Approval Letter. [FDA Web site] Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761137Orig1s000Approv.pdf. Accessed on February 18, 2020.

US Food and Drug Administration. Center for Drug Evaluation and Research. PADCEV™ (enfortumab vedotin-ejfv). Product Labeling. [FDA Web site]. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761137Orig1s000Lbl.pdf
Accessed on February 18, 2020.



Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

C65.1 Malignant neoplasm of right renal pelvis

C65.2 Malignant neoplasm of left renal pelvis

C65.9 Malignant neoplasm of unspecified renal pelvis

C66.1 Malignant neoplasm of right ureter

C66.2 Malignant neoplasm of left ureter

C66.9 Malignant neoplasm of unspecified ureter

C67.0 Malignant neoplasm of trigone of bladder

C67.1 Malignant neoplasm of dome of bladder

C67.2 Malignant neoplasm of lateral wall of bladder

C67.3 Malignant neoplasm of anterior wall of bladder

C67.4 Malignant neoplasm of posterior wall of bladder

C67.5 Malignant neoplasm of bladder neck

C67.6 Malignant neoplasm of ureteric orifice

C67.8 Malignant neoplasm of overlapping sites of bladder

C67.9 Malignant neoplasm of bladder, unspecified

C68.0 Malignant neoplasm of urethra

C68.8 Malignant neoplasm of overlapping sites of urinary organs

C68.9 Malignant neoplasm of urinary organ, unspecified




HCPCS Level II Code Number(s)

J9177 Injection, enfortumab vedotin-ejfv, 0.25 mg


Revenue Code Number(s)

N/A


Misc Code

N/A:

N/A


Coding and Billing Requirements



Policy History

Revision from 08.00.43a:
04/06/2020This version of the policy will become effective 07/01/2020.

This policy has been identified for a HCPCS code update, effective 07/01/2020.

The following HCPCS code has been added to this policy: J9177.

The following HCPCS codes has been deleted from the policy: C9399 & J3590.


08.00.43
04/06/2020This version of the policy will become effective 04/06/2020. The following new policy has been developed to communicate Company's coverage criteria for enfortumab vedotin-ejfv (Padcev™) intravenous infusion.
Version Effective Date: 07/01/2020
Version Issued Date: 07/03/2020
Version Reissued Date: N/A



2017 AmeriHealth.