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TOPLINE:

Adding serplulimab to chemotherapy extended median overall survival by nearly 5 months compared with chemotherapy alone in patients with previously untreated extensive-stage small cell lung cancer (SCLC) over a 4-year follow-up, according to findings from the phase 3 randomized ASTRUM-005 trial. The combination therapy was associated with threefold higher survival rates at 4 years, with nearly 22% vs 7.2% of patients in the serplulimab group alive vs the placebo group.

METHODOLOGY:

• Earlier findings from ASTRUM-005 reported a 2-year survival benefit when adding serplulimab to chemotherapy in previously untreated extensive-stage SCLC, but longer-term outcomes remain unclear.
• Researchers conducted an international, double-blind, phase 3 randomized clinical trial enrolling 585 patients with previously untreated extensive-stage SCLC from 114 hospitals across China, Russia, Ukraine, Poland, Turkey, and Georgia between September 12, 2019, and April 27, 2021.
• Participants were randomly assigned in a 2:1 ratio to receive intravenous serplulimab (4.5 mg/kg) or placebo, combined with up to four cycles of carboplatin and etoposide administered every 3 weeks, with 389 patients assigned to the serplulimab group and 196 to the placebo group.
• The primary endpoint was overall survival, with secondary endpoints including progression-free survival (PFS), objective response rate, safety, and patient-reported outcomes (PROs).
• Patients were followed through May 7, 2024, with a median follow-up duration of 42.4 months.

TAKEAWAY:

• Serplulimab plus chemotherapy was associated with significantly improved median overall survival (15.8 vs 11.1 months), representing a 40% reduction in the risk for death (hazard ratio [HR], 0.60; P < .001).
• Serplulimab was also associated with significantly improved median PFS (5.8 vs 4.3 months; HR, 0.47), as well as higher rates of confirmed objective responses (68.9% vs 58.7%; odds ratio [OR], 1.58).
• The overall survival benefit from adding serplulimab to chemotherapy was generally consistent across patient subgroups, including those with liver metastasis (HR, 0.58) as well as across different racial groups and PD-L1 expression levels.
• Grade 3 or higher treatment-related adverse events occurred in 35% vs 29.1% of patients in the serplulimab group vs the placebo group, with immune-related adverse events reported in 38% vs about 19%, respectively. A PRO analysis revealed consistent trends of improved overall health, dyspnea, and pain in both groups and faster recovery from alopecia in the serplulimab group.

IN PRACTICE:

“This secondary analysis of a randomized clinical trial demonstrated long-term benefit from adding serplulimab to chemotherapy for previously untreated patients with [extensive-stage] SCLC,” the study authors concluded.

The final analysis of ASTRUM-005 “provides long-term data supporting serplulimab as a therapeutic option in extensive-stage small cell lung cancer,” wrote Narjust Florez, MD, Dana-Farber Cancer Institute, Boston, in a related editorial. “From a clinical perspective, these findings are unlikely to change current practice but rather reinforce it.”

SOURCE:

The study, led by Jingjing Liu, MD, Department of Oncology, Jilin Cancer Hospital, Changchun, China, was published online on June 4 in JAMA Oncology.

LIMITATIONS:

The authors noted that the study did not include head-to-head comparisons with other PD-1 or PD-L1 inhibitors, which prevents direct assessment of serplulimab’s relative efficacy compared with other immunotherapy agents. The study did not enroll patients with an Eastern Cooperative Oncology Group performance status of 2 or greater, limiting the applicability of findings to a patient population with poorer functional status. The time-to-deterioration analysis approach used may result in an optimistic estimation of outcomes, though this potential bias would be expected to apply similarly to both treatment groups and is unlikely to notably affect comparative interpretation.

DISCLOSURES:

Shanghai Henlius Biotech, Inc. provided support for the study. Haoyu Yu, Jing Li, Xinyi Yang, and Qingyu Wang disclosed being employees of Shanghai Henlius Biotech during the conduct of the study. Jun Zhu reported being employed by Shanghai Henlius Biotech. No other conflicts of interest were reported by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.