FDA Approval Insights: Lurbinectedin in Metastatic SCLC


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In our exclusive interview, Jacob Sands, MD, discusses the FDA approval of lurbinectedin in small cell lung cancer and shed light on key findings from the phase 2 basket trial that served as the basis for the approval.

Welcome to a very special edition of OncLive® On Air! I’m your host today, Caroline Seymour.

OncLive® On Air is a podcast from OncLive, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

Today, we had the pleasure of speaking with Jacob Sands, MD, a physician at Dana-Farber Cancer Institute, and an instructor in medicine at Harvard Medical School, to discuss the FDA approval of lurbinectedin (Zepzelca) for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression following platinum-based chemotherapy.

The agent was approved on June 15, 2020 under the FDA’s Accelerated Approval Program, which allows for the conditional approval of a therapy that fills an unmet need for a serious or life-threatening disease or condition.

It has been difficult to develop an effective and tolerable second-line therapy for patients with resistant and rapidly-progressive SCLC, explained Sands, and the approval of lurbinectedin has helped to address this area of unmet need.

The regulatory decision is based on data from an open-label, single-arm, phase 2 basket trial (NCT2454972) of 105 patients with SCLC who progressed on platinum-containing therapy.

In the trial, patients received 3.2 mg/m2 of lurbinectedin as a 1-hour intravenous infusion once every 3 weeks until either progressive disease or unacceptable toxicity.

Results from the trial showed that treatment with lurbinectedin led to an overall response rate (ORR) of 35.2% and a disease control rate of 68.6%. Moreover, a median duration of response of 5.3 months was reported with lurbinectedin per investigator assessment.

Additional results showed that the majority of the patients, or 65%, experienced a reduction in tumor size. Notably, responses were reported in 5 of 8 patients in whom prior immunotherapy had failed. A total of 28 patients, or 26.7%, experienced disease progression and 5 patients were not evaluable.

Earlier results showed that response rates with lurbinectedin were higher in patients with platinum-sensitive disease. Among those patients, the ORR was 45% versus 22.2% in those with platinum-resistant disease.

The median progression-free survival (PFS) was 3.9 months and the 6-month PFS rate was 33.6%. In those with platinum-sensitive disease, the median PFS was 4.6 months and the 6-month PFS rate was 44.6%. In those with platinum-resistant disease, the median PFS was 2.6 months and the 6-month PFS rate was 18.8 months.

At a median follow-up of 17.1 months, the median overall survival (OS) with lurbinectedin was 9.3 months; the 12-month OS rate was 34.2%. In patients who were platinum sensitive, the median OS was 11.9 months versus 5.0 months in patients who were platinum resistant.

Regarding safety, all-grade adverse effects (AEs) were reported in 84.8% of patients. The most common grade 1/2 AEs with the agent included fatigue, nausea, decreased appetite, vomiting, diarrhea, constipation, and neutropenia.

A total of 34.3% of patients experienced a grade 3 or greater AE. The most commonly reported grade 3/4 AEs were hematologic, including anemia, leucopenia, neutropenia, and thrombocytopenia.

Serious treatment-related AEs were reported in 10.5% of patients. Of these effects, neutropenia and febrile neutropenia were the most commonly reported.

Discontinuations, dose delays, and dose reductions, related to AEs were reported in 1.9%, 22.1%, and 26.3% of patients, respectively. No toxicity-related deaths were reported.

In our exclusive interview, Sands discussed the FDA approval of lurbinectedin in small cell lung cancer and shed light on key findings from the phase 2 basket trial that served as the basis for the approval.

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