Relapsed and refractory systemic therapy real-world outcomes in the Canadian small cell lung cancer database (CASCADE)

BackgroundFor several decades, the management of recurrent small cell lung cancer (SCLC) involved several chemotherapy regimens. Recently, newer agents have shown promise, including lurbinectedin, tarlatamab, and ifinatamab deruxtecan, among others, which raises interest in real-world outcomes in relapse and platinum-refractory settings.MethodsWe evaluated preliminary real-world Canadian data from CASCADE for demographics, treatments, and outcomes of patients (pts) who relapsed after first-line (1L) platinum-based regimens. We included pts initially diagnosed between 2001-2022 as limited stage (LS) or extensive stage (ES) disease.ResultsOf 2472 pts from sites with 2L/3L data, median age was 67 years; 50% were females; 2112 (85%) were treated with first-line platinum-based chemotherapy (with or without radiation or immunotherapy, including 1496 ES and 616 LS pts). With a median follow-up time of 85.9 months (mos), 554 died without document relapse, 156 had no documented relapse/death, and 1402 had documented relapse dates. Of those 1402 with relapse, 840 (60%) received no further systemic treatment, 314 (22%) received 2L platinum-based regimen, and 221 (16%) received only non-platinum regimens subsequently. 2L platinum-receiving pts had a median overall survival (mOS) from time of 2L start of 8.3 mos (95% CI 7.3 – 9.2) vs. non-platinum regimens, mOS 4.7 mos (95% CI 3.8 – 5.5). Among all 1402 relapsed pts, 550 (39%) received 2L therapy: median progression-free survival (mPFS) for any 2L therapy was 3.1 mos (95% CI 2.7 – 3.5, n = 372); mOS was 6.6 mos (95% CI 5.9 – 7.2). In contrast, only 169 (12%) received 3L therapy: mPFS was 1.9 mos (95% CI 1.6-2.5, n = 87); mOS was 5.4 mos (95% CI 4.6 – 6.6). At time of platinum-refractory disease (n=1365), 308 (23%) received another line of therapy, with mPFS of 1.9 mos (95% CI 1.7-2.3, n = 211) and mOS of 4.9 mos (95% CI 4.3 – 5.4). Updated results will be presented as additional relapse dates are confirmed.ConclusionsThere are high attrition rates for subsequent treatment lines in relapse/refractory SCLC with short PFS/OS in the highly selected patients who received subsequent therapy. There is a dire need for effective yet tolerable treatments in this setting.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureS. Moore: Financial Interests, Personal, Advisory Board: AstraZeneca Canada Inc., Amgen, Bristol Myers Squibb; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca Canada Inc., Merck. R. Rittberg: Financial Interests, Personal, Advisory Board: AstraZeneca Canada Inc., Merck; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca Canada Inc., Pfizer, Novartis. B.H. Lok: Financial Interests, Personal and Institutional, Research Grant: Pfizer, AstraZeneca; Financial Interests, Personal, Funding: AstraZeneca, Daiichi Sankyo; Non-Financial Interests, Personal, Non-financial benefits: AstraZeneca. D. Dawe: Financial Interests, Personal, Advisory Board, Compensated for advisory board attendance: AstraZeneca, Merck, Pfizer, Jazz Pharmaceuticals, Roche, Novartis, Johnson & Johnson; Financial Interests, Personal, Other, Creation of educational content: Bristol Myers Squibb; Financial Interests, Institutional, Coordinating PI, Two research grants, totaling $60,000 over the last 5 years: AstraZeneca; Non-Financial Interests, Leadership Role, Chair of the CAMO Fellowship Committee: Canadian Association of Medical Oncologists; Non-Financial Interests, Project Lead, Chair of the Small Cell Lung Cancer Working Group: Canadian Cancer Trials Group. P. Wheatley-Price: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Merck, Amgen, Lilly, Sanofi, Pfizer, Janssen; Financial Interests, Personal, Advisory Board, Advisory Board: SteriMax, GSK; Financial Interests, Institutional, Local PI: Turning Point, Jazz Pharmaceuticals, Novartis, AstraZeneca. G. Liu: Financial Interests, Personal, Advisory Board: AnHeart Therapeutics Inc., Amgen, AstraZeneca, Bayer, EMD Serono, Jazz, Johnson and Johnson, Merck, Novartis, Pfizer, Roche, Sterimax, Takeda; Financial Interests, Institutional, Principal Investigator: Takeda, AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Boehringer Ingelheim, Pfizer, AstraZeneca, Takeda. All other authors have declared no conflicts of interest.