Real-World Serplulimab Combo Outcomes Validate ASTRUM-005 Trial in ES-SCLC

First-line serplulimab (Hetronifly) plus chemotherapy yielded real-world survival outcomes consistent with the pivotal phase 3 ASTRUM-005 trial (NCT04063163) in patients with extensive-stage small cell lung cancer (ES-SCLC), according to the nationwide observational ASTRUM-005R study (NCT06748495) published in BMC Medicine.¹

What did the real-world study show?

Among 635 patients with ES-SCLC, the median overall survival (OS) for the entire cohort was 17.20 months (95% CI, 15.43-19.77); it was 18.27 months (95% CI, 15.97-22.77) in the real-world cohort and 15.0 months (95% CI, 12.97-17.07) in the randomized controlled trial (RCT)-regimen cohort (HR, 0.83; 95% CI, 0.61-1.12; P = .227). The median real-world progression-free survival (PFS) was 8.17 months (95% CI, 7.40-9.20). The objective response rate (ORR) was 69.05% (95% CI, 65.28%-72.64%), with comparable efficacy observed between the cohort treated according to the ASTRUM-005 trial regimen cohort and the real-world cohort. An ECOG performance status of 2 or higher and liver metastases independently predicted higher mortality.

The safety profile was manageable and consistent with the known profile of serplulimab plus chemotherapy. Adverse effects (AEs) of any grade occurred in 53.70% of patients, which included grade 3 or higher AEs in 16.22%. The most common grade 3 or higher toxicities included decreased white cell count (5.51%), neutropenia (4.88%), and decreased platelet count (2.20%).

How did outcomes compare with the ASTRUM-005 trial?

To benchmark the real-world results against the pivotal trial, the investigators used a matching-adjusted indirect comparison (MAIC) that weighed eligible real-world patients to the aggregate baseline profile of ASTRUM-005. In this analysis, OS in the cohort treated with the trial regimen was comparable to that of the serplulimab arm of the pivotal trial (weighted log-rank P = .784). In the randomized phase 3 ASTRUM-005 trial, adding serplulimab to chemotherapy significantly improved OS compared with chemotherapy alone in patients with previously untreated ES-SCLC, supporting its use as a first-line option.²

“This large-scale, multicenter, observational study provides compelling real-world evidence confirming the effectiveness and tolerability of serplulimab-based chemoimmunotherapy as a first-line treatment for ES-SCLC,” lead study author Lin Wu, from the Department of Thoracic Medical Oncology at Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, wrote with coauthors in the publication.¹ “Additionally, exploratory findings suggest that serplulimab maintenance or continuation beyond initial progression may yield incremental survival benefits and warrant further prospective validation. Collectively, this study represents a critical step toward evidence-based immunotherapy for ES-SCLC in the real world.”

What was the study design?

The nationwide, observational study enrolled patients with ES-SCLC treated with serplulimab and investigator-selected chemotherapy across 14 sites in China. For the analyses, patients were grouped by alignment with the ASTRUM-005 trial regimen into either the RCT-regimen cohort (n = 133) or the real-world regimen cohort (n = 502).

In the RCT-regimen cohort, patients received serplulimab plus carboplatin and etoposide with 4 cycles. In the real-world cohort, patients deviated from this protocol, receiving more than 4 combination cycles or using alternative platinum agents.

Patients 18 years and older with pathologically confirmed ES-SCLC, at least 2 cycles of serplulimab-based treatment, and at least 1 post-baseline tumor evaluation in the case of measurable disease were eligible for enrollment on the study. Those with concurrent active malignancies or who refused follow-up were excluded.

The median age was 62 years (range, 48-82) in the randomized clinical trial population and 63 years (range, 30-84) in the real-world cohort. Across each respective population, most patients had an ECOG performance status of 1 (72.18% vs 59.16%), a history of smoking (75.19% vs 67.93%), and stage IV disease (93.98% vs 91.04%).

The primary end points were OS and real-world PFS. Secondary end points included ORR and safety.

References

1. Wu L, Hu C, Su W, et al. Real-world serplulimab plus chemotherapy for extensive-stage small cell lung cancer in China: an external validation of ASTRUM-005 trial. BMC Med. Published online July 15, 2026. doi:10.1186/s12916-026-05055-9
2. Cheng Y, Zhang S, Han L, et al. First-line serplulimab plus chemotherapy in extensive-stage small-cell lung cancer: updated results and biomarker analysis from the ASTRUM-005 randomized clinical trial. Cancer Commun (Lond). Published online May 29, 2025. doi:10.1002/cac2.70032