Second-Line & Later Therapies Show Promising Outcomes in Small Cell Lung Cancer

Photo Credit: iStock.com/Mohammed Haneefa Nizamudeen

Lurbinectedin showed clinical benefit across therapy lines in small cell lung cancer, with best responses seen in later lines and with prior immunotherapy exposure.

According to research presented at ASCO 2025, small cell lung cancer (SCLC) remains a particularly difficult disease to treat, with limited therapeutic options and generally poor survival outcomes. The researchers noted that although lurbinectedin (Zepzelca) has been approved for use following platinum-based chemotherapy, real-world data on its effectiveness and the optimal timing for its administration are limited.

To address this gap, Belal C. Krayim, MD, and colleagues conducted a retrospective multi-center study to assess how treatment outcomes with lurbinectedin vary across different lines of therapy in patients with SCLC.

The study reviewed data from 61 patients treated with lurbinectedin between January 2020 and December 2024, with 56 patients being evaluable for analysis. Most patients were male (55%), with a median age of 65. Lurbinectedin was primarily used as a second-line treatment (38 patients), but also in third-line (15 patients) and later lines (3 patients).

Of note, key clinical endpoints included overall survival (OS), progression-free survival (PFS), treatment duration, and overall response rate (ORR), which were analyzed using RECIST v1.1 criteria and Kaplan-Meier survival estimates.

Across all treatment lines, the ORR was 37.5%, with the highest response observed in fourth/fifth-line therapy (66.7%), followed by second-line (42.1%) and third-line (20%). Further findings showed median overall survival was 7.1 months, and median treatment duration was 4.3 months. Notably, brain metastases, present in half of the patients, did not appear to influence treatment outcomes.

Patients with prior immunotherapy exposure—accounting for 68% of the cohort—experienced longer treatment durations (4.6 months vs 2.3 months) and improved OS (8.8 months vs 5.8 months), although these trends did not reach statistical significance.

Overall, lurbinectedin was generally well tolerated, with hematologic toxicities being the most common adverse events. Most were mild to moderate (Grade 1–2), including anemia, thrombocytopenia, and neutropenia. Importantly, no severe Grade 4 toxicities were observed.

“Lurbinectedin demonstrated meaningful clinical activity in second-line therapy for SCLC, while also showing durable responses in heavily pretreated cases,” the study authors concluded. “These findings support the consideration of lurbinectedin beyond second-line therapy in selected SCLC patients, though larger prospective studies are needed to validate these response patterns.”