Serplulimab vs. placebo combined with chemotherapy as first-line treatment for extensive-stage small-cell lung cancer: Extended follow-up results and patient-reported outcomes from the international phase 3 ASTRUM-005 study.
Authors: Cheng Ying , Han Liang , Wu Lin , Chen Jun , Sun Hongmei , Wen Guilan , Ji Yinghua , Zimina Anastasia V. , Shi Jianhua , Pan Zhijie , Shi Jinsheng , Wang Xicheng , Bai Yuansong , Melkadze Tamar , Pan Yueyin , Min Xuhong , Viguro Maksym , Li Jing , Wang Qingyu , Zhu Jun ,   ASTRUM-005 Study Group
Published: June 2024

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Background: ASTRUM-005 is a randomized, double-blind, phase 3 trial comparing efficacy and safety of serplulimab (a novel anti-PD-1 antibody) plus chemotherapy (chemo) vs. placebo plus chemo as first-line therapy for extensive-stage small-cell lung cancer (ES-SCLC). Interim analysis presented at 2022 ASCO Annual Meeting showed significantly prolonged overall survival (OS) in the serplulimab arm. Continuing improvements were seen in all efficacy endpoints in an updated analysis reported at ESMO Asia Congress 2022. Here we present the updated results with an extended follow-up duration of 31.6 months and the previously undisclosed patient-reported outcomes (PROs). Methods: 585 patients with ES-SCLC who had not received prior systemic therapy were randomized 2:1 (serplulimab arm, n = 389; placebo arm, n = 196) to receive serplulimab 4.5 mg/kg or placebo intravenously every 3 weeks. All patients received up to 4 cycles of intravenous carboplatin and etoposide every 3 weeks. Stratification factors were PD-L1 expression level, brain metastases, and age. The primary endpoint was OS. PROs were assessed using EORTC QLQ-C30, EORTC QLQ-LC13, and EQ-5D-5L questionnaires. Results: By the data cutoff of June 13, 2023, 267 (68.6%) patients in the serplulimab arm and 160 (81.6%) in the placebo arm had died. Median OS was markedly longer in the serplulimab arm than that in the placebo arm (15.8 vs.11.1 months; stratified HR 0.61, 95% CI 0.50–0.74). Subgroup analysis by race showed similar trends of a prolonged median OS in Asians (unstratified HR 0.61, 95% CI 0.48–0.77) and non-Asians (all were White; unstratified HR 0.57, 95% CI 0.39–0.83). Estimated OS rate at 3 years was 24.6% (95% CI 19.5–30.1) and 9.8% (95% CI 5.6–15.4) in the respective arms. By-visit longitudinal changes in all domains of the 3 questionnaires were comparable between arms. Least square mean (LSM) changes from baseline to week 18 in QLQ-C30 functional and symptom domains, QLQ-LC13 symptom domains, and EQ-5D-5L VAS were similar and generally improved in both arms, with more pronounced and persistent amelioration in “pain in other parts” symptom domain for the serplulimab arm (difference in LSM change, −6.37 [95% CI −11.59 to −1.15], p = 0.0170). Time to deterioration was similar between arms: median, not reached (NR) vs. NR for global health status/quality of life (HR 0.90, 95% CI 0.59–1.39), physical functioning (HR 1.01, 95% CI 0.61–1.65), and role functioning (HR 1.17, 95% CI 0.74–1.87). Conclusions: With extended follow-up, the survival benefits brought by the addition of serplulimab were maintained in the first-line therapy of ES-SCLC. PROs were not adversely impacted, and pain in other parts was significantly improved. All these results support serplulimab plus chemo as a promising first-line treatment option for ES-SCLC. Clinical trial information: NCT04063163 .