Clinical outcomes to second-line treatment, after failing chemoimmunotherapy, in ES-SCLC

Abstract

BACKGROUND: In extensive-stage small cell lung cancer (ES-SCLC), chemoimmunotherapy (CIO) has become the first-line (1L) standard of care. Limited data on response and survival outcomes after CIO in subsequent treatment lines are available. We assessed second-line (2L) outcomes for patients (pts) with ES-SCLC following progression after initial CIO. METHODS: We retrospectively extracted multi-centre patient data from the Australian Registry and Biobank of Thoracic Cancers (AURORA). Population characteristics and treatment outcomes were summarized with descriptive statistics. Survival was estimated using the Kaplan-Meier method, with Cox proportional hazards model for estimating the effects of covariates. RESULTS: We included 111 pts from 10 Australian centers. Median age was 65 years; 58% male, 96% current or past smokers, and 74% were ECOG PS <=1 at initial presentation. At diagnosis, 51% of the patients had liver, and 14% had brain metastasis. A median number of 8 cycles (Q1-Q3 5-9.8) of IO (97% Atezolizumab) were administered before starting 2L treatment, including induction therapy. The most frequent 2L regimens were Lurbinectedin (32%), re-challenge with Carboplatin/Etoposide (21%), CAV (Cyclophosphamide/ Doxorubicin/ Vincristine) (20%), and Topotecan (9%). In the re-challenge cohort, the median time from 1L platinum to 2L platinum was 192 days (Q1-Q3 156-308; 65% >= 180 days). Across all treatment groups, the 2L objective response rate was 22%. Median 2L duration of response was 2.2 months (CI 95% 1.7-3.3) and median 2L progression-free survival was 2.9 months (CI 95% 2.5-3.7). Median 2L overall survival was 5.8 months (CI 95% 4.6-6.4), with a 6-month and 12-month survival of 49% and 14%, respectively. Twenty-six pts (23%) subsequently went on to receive third-line therapy, 8 pts (7%) proceeded to fourth-line, and 2 pts (2%) advanced to a fifth-line treatment setting. CONCLUSIONS: Following CIO in the first-line context, 2L survival outcomes resemble those of previously published chemotherapy-alone first-line patients. In this multicentre cohort, 2L-treatment response and survival remain poor in ES-SCLC, suggesting a limited residual impact of immunotherapy.