Updated analysis from NEJ045A study: Safety and efficacy of durvalumab plus carboplatin and etoposide for previously untreated extensive-stage small-cell lung cancer patients with a poor performance status.

Abstract

8557 Background: Although the combination of an anti-PD-L1 antibody and platinum-based chemotherapy has become the standard care for extensive-stage small-cell lung cancer (ES-SCLC) patients (pts), its safety and efficacy for those with a poor PS are unclear. In the NEJ045A study, by adjusting the doses of carboplatin (CBDCA) and etoposide (ETP), durvalumab (DUR) plus CBDCA and ETP demonstrated tolerability and efficacy for ES-SCLC pts with a poor PS, meeting the primary endpoint of tolerability. Here, we report the updated data from NEJ045A, including the long-term effects of ICIs. Methods: Previously untreated ES-SCLC pts with PS 2–3 were enrolled. Eligible pts received 1500 mg DUR plus CBDCA and ETP every 3 to 4 weeks for up to 4 cycles, followed by DUR maintenance therapy. Initial dosages of CBDCA and ETP were AUC 4 and 80 mg/m 2 in PS 2 and AUC 3 and 60 mg/m 2 in PS 3. The dosages for the subsequent cycles were adaptively determined based on the adverse events (AEs) of the previous cycles. Results: From April 2021 to October 2023, 57 pts (43 pts with PS 2 and 14 pts with PS 3) were enrolled. At the data cutoff (Oct 3rd, 2024), the median follow-up period for overall survival among patients with censored data was 23.4 months (12.9-32.7) in the FAS population. The median age was 74 years old (range 55-86). 79% was male. The median number of cycles of induction therapy was 4 (range 1-4), and the median number of cycles of durvalumab maintenance was 3 (range 1-16) in PS 2 and 7 in PS 3 (1-22). A total of 34 patients (64%) completed induction therapy, comprising 28 pts (67%) in PS 2 and 6 pts (50%) in PS 3. Doses of CBDCA and/or ETP were increased during induction therapy in 24% of PS 2, and 18% of PS 3. Updated median PFS in PS 2 and PS 3 were 4.5 months (95% CI, 3.1-5.8) and 4.5 months (95% CI, 1.4-8.2). The 1-year survival rates in PS 2 and PS 3 were 50% (95% CI, 37.0-67.7) and 18% (95% CI, 5.2-63.7). Updated median OS in PS 2 and PS 3 were 11.3 months (95% CI, 6.7- 16.1) and 5.1 months (95% CI, 2.1-8.5). Patients who completed induction therapy demonstrated longer OS compared to those who did not (median OS, 15.0 vs. 3.8 months). Treatment was discontinued in 100% of PS 2 and 93% of PS 3, and the reasons for discontinuation (PD/AE/other) were 79%/12%/9% in PS 2 and 38%/54%/8% in PS 3. Conclusions: DUR + CBDCA + ETP therapy was well tolerated for ES-SCLC with poor PS, and completion of induction therapy was associated with an improvement in OS. Clinical trial information: CRB3180025 .