Serplulimab for First-Line Treatment of Extensive-Stage Small-Cell Lung Cancer
Serplulimab (a PD-1 inhibitor) combined with carboplatin and etoposide, followed by maintenance serplulimab, is an effective first-line treatment option for extensive-stage small-cell lung cancer (ES-SCLC), though it is not currently included in the most recent ASCO or NCCN guidelines as a preferred regimen.
Recommended Dosing Regimen
Based on the ASTRUM-005 trial 1, the standard serplulimab regimen is:
Induction phase: Serplulimab 4.5 mg/kg IV every 3 weeks combined with:
- Carboplatin (AUC 5) IV every 3 weeks
- Etoposide 100 mg/m² IV days 1-3 every 3 weeks
- Duration: 4 cycles (up to 12 weeks)
Maintenance phase: Serplulimab 4.5 mg/kg IV every 3 weeks as monotherapy until disease progression or unacceptable toxicity
Evidence Quality and Guideline Status
While the 2023 ASCO-Ontario Health guideline 2 recommends first-line chemo-immunotherapy for ES-SCLC, it specifically endorses only atezolizumab or durvalumab as preferred immunotherapy agents (Category 1, High evidence quality, Strong recommendation). The guideline does mention the ASTRUM-005 trial showing serplulimab's efficacy (median OS 15.4 vs 10.9 months, HR 0.63, p<0.001; median PFS 5.7 vs 4.3 months, HR 0.48) 2, but serplulimab is not included in the formal recommendations.
The NCCN 2022 guidelines 3 similarly recommend only atezolizumab or durvalumab plus chemotherapy as Category 1 preferred regimens for ES-SCLC, with no mention of serplulimab.
Clinical Efficacy
The ASTRUM-005 phase 3 trial 1 demonstrated robust efficacy in 585 treatment-naïve ES-SCLC patients:
- Overall survival: 15.4 months (serplulimab) vs 10.9 months (placebo), HR 0.63 (95% CI 0.49-0.82, p<0.001)
- Progression-free survival: 5.7 months vs 4.3 months, HR 0.48 (95% CI 0.38-0.59)
- Objective response rate: 80.2% vs 70.4%
Updated results with 19.8 months median follow-up 4 confirmed sustained benefit with median OS of 15.8 months in the serplulimab group.
Safety Profile
Treatment-related adverse events grade ≥3 occurred in 33.2% of serplulimab patients vs 27.6% with placebo 1. The safety profile was comparable to other PD-1/PD-L1 inhibitors used in ES-SCLC, with immune-related adverse events being manageable.
A recent real-world comparison 5 showed no significant differences in PFS between serplulimab and PD-L1 inhibitors (durvalumab, atezolizumab, adebrelimab), though adebrelimab demonstrated superior OS compared to serplulimab (23.2 vs 15.0 months, p=0.029).
Clinical Context and Positioning
The key limitation is that serplulimab lacks FDA approval in the United States and is not endorsed by major Western guidelines. The ASTRUM-005 trial was conducted primarily in China 1, and serplulimab appears to be used predominantly in Asian markets.
For patients in regions where serplulimab is available, it represents a viable alternative to atezolizumab or durvalumab based on comparable efficacy demonstrated in the phase 3 trial. However, in the United States and most Western countries, clinicians should prioritize guideline-recommended regimens: carboplatin/etoposide plus either atezolizumab or durvalumab 2, 3.
Predictive Biomarkers
Exploratory analysis 4 identified potential predictive markers for serplulimab benefit:
- RB1 mutations associated with improved outcomes
- Notch pathway mutations linked to better response
- A 15-protein signature correlated with longer OS and PFS
- Baseline neutrophil-to-lymphocyte ratio and LDH as independent prognostic factors
These biomarkers require validation before clinical implementation.
Important Caveats
- Serplulimab is not FDA-approved and not included in ASCO or NCCN guidelines as a recommended option
- Cost-effectiveness analyses 6, 7, 8 suggest serplulimab may not be cost-effective even in China without significant price reductions
- Direct head-to-head comparisons with atezolizumab or durvalumab are lacking
- The evidence base is primarily from a single phase 3 trial conducted in Asian populations
For clinical practice in the United States, use carboplatin/etoposide plus atezolizumab (1200 mg maintenance) or durvalumab as first-line therapy for ES-SCLC 2, 3. Serplulimab should only be considered in regions where it has regulatory approval and when guideline-recommended agents are unavailable.