Relapsed small-cell lung cancer: a disease of continued unmet need.

Despite immunotherapeutic advancements in the treatment of front-line extensive-stage small-cell lung cancer (SCLC), the majority of patients will have disease progression within 6 months. 1 Liu SV Reck M Mansfield AS et al. Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung cancer treated with atezolizumab, carboplatin, and etoposide (IMpower133). J Clin Oncol. 2021; 39: 619-630 Crossref PubMed Scopus (201) Google Scholar , 2 Goldman JW Dvorkin M Chen Y et al. Durvalumab, with or without tremelimumab, plus platinum–etoposide versus platinum–etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021; 22: 51-65 Summary Full Text Full Text PDF PubMed Scopus (247) Google Scholar Such a reality places increased importance on identifying effective and tolerable systemic therapy options in this key relapsed setting. Lurbinectedin, a selective oncogenic transcription inhibitor, was approved by the US Food and Drug Administration for patients with extensive-stage SCLC with disease progression on or after platinum-based chemotherapy on the basis of results from a single-arm phase 2 basket trial. In this study, 35·2% of patients had an overall response, with a median progression-free survival of 4·6 months and overall survival of 9·3 months. 3 Trigo J Subbiah V Besse B et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020; 21: 645-654 Summary Full Text Full Text PDF PubMed Scopus (174) Google Scholar Haematological abnormalities were the most common treatment-associated toxicity, with grade 3 or worse neutropenia occurring in 46% of patients. With these encouraging results, lurbinectedin quickly ascended as a potential therapeutic alternative to topotecan in the relapsed setting, despite absence of randomised phase 3 data confirming superiority in survival outcomes. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trialCombination therapy with lurbinectedin plus doxorubicin did not improve overall survival versus control in patients with relapsed SCLC. However, lurbinectedin plus doxorubicin showed a favourable haematological safety profile compared with control. Full-Text PDF