Lurbinectedin (Zepzelca)

Number: 0978

Policy

Aetna considers lurbinectedin (Zepzelca) medically necessary for subsequent treatment of small cell lung cancer as a single agent in any of the following settings:

• For relapse following complete or partial response or stable disease with initial treatment; or
• For primary progressive disease; or
• For metastatic disease following disease progression on or after platinum-based chemotherapy.

Aetna considers continuation of lurbinectedin (Zepzelca) medically necessary for members with a medically necessary indication when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Aetna considers all other indications for Zepzelca (lurbinectedin) experimental and investigational and not medically necessary.

Dosing Recommendations

Recommended dosage for SCLC: 3.2 mg/m² every 21 days administed as an intravenous infusion over 60 minutes.

Source: Jazz Pharmaceuticals 2020.

Background

U.S. Food and Drug Administration (FDA)-Approved Indication

• Zepzelca is indicated for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.

Compendial Uses

• Relapsed small cell lung cancer
• Primary progressive small cell lung cancer

Small cell lung cancer (SCLC) represents 15 percent of all lung cancers and occurs almost exclusively in smokers. It is distinguished from non-small cell lung cancer by its rapid doubling time, high growth fraction, and the early development of widespread metastases. Although considered highly responsive to chemotherapy and radiotherapy, SCLC usually recurs within 14 to 15 months for patients with limited-stage SCLC and five to six months for patients with extensive-stage SCLC. The median survival of patients with relapsed SCLC ranges from two to six months. The most important factors affecting prognosis are performance status, tumor extent (i.e., limited versus extensive), and time to relapse after first-line therapy. Similarly, the likelihood of an objective response to second-line therapy depends upon the time from last therapy to relapse, the response to initial treatment, and the performance status.

On June 15, 2020, the Food and Drug Administration granted accelerated approval to lurbinectedin (Zepzelca), a selective inhibitor of oncogenic transcription, for adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. The FDA approval was based on results from PM1183-B-005-14 (Study B-005; NCT02454972; Trigo 2020), a multicenter, open-label, multi-cohort basket trial evaluating Zepzelca as a single agent in patients with advanced or metastatic solid tumors. A basket trial is a type of clinical trial that tests how well a new drug or other substance works in patients who have different types of cancer that all have the same mutation or biomarker. Patients received a median of 4 cycles of Zepzelca (range 1 to 24 cycles). Patients were recruited from 26 hospitals in six European countries and the USA. Adults (aged ≥18 years) with a pathologically proven diagnosis of SCLC, Eastern Cooperative Oncology Group performance status of 2 or lower, measurable disease as per Response Criteria in Solid Tumors (RECIST) version 1.1, absence of brain metastasis, adequate organ function, and pre-treated with only one previous chemotherapy-containing line of treatment (minimum 3 weeks before study initiation) were eligible. The trial excluded patients with central nervous system (CNS) involvement, grade ≥3 dyspnea, daily intermittent oxygen requirement, hepatitis or cirrhosis, and immunocompromised patients. Tumor assessments were conducted every 6 weeks for the first 18 weeks and every 9 weeks thereafter. The major efficacy outcome measure was confirmed investigator-assessed overall response rate (ORR). Additional efficacy outcome measures included duration of response (DoR), and an Independent Review Committee. A cohort of patients with small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy received Zepzelca 3.2 mg/m² administered as a 1-h intravenous infusion every 3 weeks (one cycle) until disease progression or unacceptable toxicity. All treated patients were analysed for activity and safety. 

Between Oct 16, 2015, and Jan 15, 2019, 105 patients were enrolled and treated with lurbinectedin. The median age was 60 years (range: 40 to 83) with 65% of patients < 65 years and 35% of patients greater than or equal to 65 years, and 60% were male. The majority (75%) of the patients were White, 1% were Asian, 1% were Black and 23% were not reported. Baseline ECOG performance status was 0 or 1 in 92% of patients, and 92% were former/current smokers. All patients received at least one line of platinum-based chemotherapy (range 1-2 lines), and prior radiotherapy had been administered to 71% of patients. Eight patients (8%) had prior immunotherapy in addition to platinum-based chemotherapy. Sixty patients (57%) had platinum-sensitive SCLC, defined as recurrence or progression ≥ 90 days after the last dose of platinum-containing therapy (chemotherapy free interval [CTFI] ≥ 90 days). The remaining 45 patients had platinum-resistant SCLC, defined as recurrence or progression < 90 days after the last dose of platinum-containing therapy (CTFI < 90 days). Median follow-up was 17·1 months (IQR 6·5-25·3).

The main efficacy outcome measures were confirmed overall response rate (ORR) determined by investigator assessment using RECIST 1.1 and response duration. Among the 105 patients, the ORR was seen in 37 patients (35%; 95% CI: 26%, 45%), with a median response duration of 5.3 months (95% CI: 4.1, 6.4). The ORR as per independent review committee was 30% (95% CI: 22%, 40%) with a median response duration of 5.1 months (95% CI: 4.9, 6.4). The most common grade 3-4 adverse events (irrespective of causality) were haematological abnormalities-namely, anaemia (in nine [9%] patients), leucopenia (30 [29%]), neutropenia (48 [46%]), and thrombocytopenia (seven [7%]). Serious treatment-related adverse events occurred in 11 (10%) patients, of which neutropenia and febrile neutropenia were the most common (five [5%] patients for each). No treatment-related deaths were reported. The authors concluded that lurbinectedin was active as second-line therapy for SCLC in terms of overall response and had an acceptable and manageable safety profile. Lurbinectedin could represent a potential new treatment for patients with SCLC, who have few options especially in the event of a relapse, and is being investigated in combination with doxorubicin as second-line therapy in a randomized phase 3 trial.

The recommended lurbinectedin dose is 3.2 mg/m² every 21 days. 

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :
Other CPT codes related to the CPB:
96413	Chemotherapy administration, intravenous infusion technique; up to 1 hour, single or initial substance/drug
96415	Chemotherapy administration, intravenous infusion technique; each additional hour (List separately in addition to code for primary procedure)
HCPCS codes covered if selection criteria are met:
J9223	Injection, lurbinectedin, 0.1 mg
Other HCPCS codes related to the CPB:
J9045	Injection, carboplatin, 50 mg
J9060	Injection, cisplatin, powder or solution, 10 mg
J9263	Injection, oxaliplatin, 0.5 mg
ICD-10 codes covered if selection criteria are met:
C34.00 - C34.92	Malignant neoplasm of bronchus and lung [small cell lung cancer (SCLC)]

The above policy is based on the following references: