Place in therapy of key treatments for platinum-sensitive, relapsed, extensive-stage small cell lung cancer with a focus on lurbinectedin: a narrative review with case studies.

Background: Virtually all patients with extensive-stage small cell lung cancer (SCLC) develop resistance to first-line platinum-based chemoimmunotherapy and experience relapse. Second-line therapy is therefore an integral part of the treatment paradigm. Methods: Evidence was reviewed for key second-line regimens recommended in major guidelines for treatment of patients with platinum-sensitive relapse (chemotherapy-free interval ≥90 days), focusing on recent prospective clinical trials and post hoc analyses. Case studies of second-line lurbinectedin are presented as examples of the current management approach to platinum-sensitive relapsed SCLC. Results: Subject to the limitations of cross-trial comparisons, the evidence review allowed us to draw broad conclusions about the place in therapy of approved options for platinum-sensitive relapse. Platinum rechallenge is more effective and better tolerated than topotecan and is a reasonable second-line choice in suitable patients. Topotecan provides modest clinical benefit and has the potential to cause dose-limiting haematological toxicities. Cyclophosphamide-doxorubicin-vincristine combination therapy offers no clear advantages over topotecan. Efficacy outcomes with second-line lurbinectedin are similar or better than those reported with platinum rechallenge, and lurbinectedin has a more favourable safety profile and simpler administration schedule. Second-line lurbinectedin preserves platinum rechallenge for later use and may resensitize tumour cells to platinum with potential survival advantages. Lurbinectedin safety is not affected by advanced age (≥65 years). Case studies highlight objective and durable responses to second-line lurbinectedin, along with good tolerability and quality of life. Conclusions: Available evidence supports second-line lurbinectedin as a useful alternative to platinum rechallenge, topotecan and cyclophosphamide-doxorubicin-vincristine in patients with platinum-sensitive relapsed SCLC.