Dr Das on the Limited Landscape of Second-line Treatment Options in ES-SCLC

Devika Das, MD, MSHQS, clinical assistant professor of hematology and oncology, University of Alabama at Birmingham (UAB) Medicine, discusses the activity and tolerability of lurbinectedin (Zepzelca) and topotecan as second-line regimens in extensive-stage small cell lung cancer (ES-SCLC).

Many patients with ES-SCLC will experience recurrence or relapse after initial treatment. However, the number of available and effective second-line options are unfortunatelylimited in this space, Das begins.

Prior to the FDA approval of lurbinectedin in 2020, the standard of care for relapsed ES-SCLC was the chemotherapy agent topotecan, Das explains. Across several randomized controlled clinical trials, the best response rate seen with this agent was 24.3% The median duration of response (DOR) is 18 weeks and median overall survival (OS) is 25 to 35 weeks. However, topotecan is associated with a high incidence of grade 3 or greater treatment-related adverse effects (AEs) in these trials.

The FDA granted accelerated approval to lurbinectedin for patients with metastatic SCLC who progressed on prior platinum-based chemotherapy based on findings from a single-arm, open-label, phase 2 basket trial (NCT02454972). In this trial of 105 patients, lurbinectedin produced an overall response rate of 35%, a median progression-free survival of 3.9 months, and a median OS of 9.3 months. Median DOR was 5.3 months with the agent. Regarding toxicities, 34.3% of patients had grade 3 or higher toxicities, and grade 1/2 toxicities were commonly observed.

A regimen’s AE profile has a substantial effect on a patient’s quality of life and greatly influences treatment selection, Das emphasizes. Although caution should be exercised when making cross-trial comparisons, lurbinectedin appears as effective and more tolerable than topotecan, Das says. Its activity in patients who are platinum-refractory also provides it with an advantage over topotecan, she adds.

Given the lack of research on potential alternatives to these agents, lurbinectedin isremains the best available option in the second line for patients who relapse within 6 months after previous treatment and cannot tolerate topotecan, Das states. An increased focus on the development of novel second-line therapeutics through clinical trials could address the continued need for more effective alternatives to lurbinectidin in relapsed ES-SCLC, Das concludes.