Benmelstobart plus anlotinib improves progression-free survival versus pembrolizumab plus placebo in first-line PD-L1-positive advanced NSCLC.

This randomised, controlled, phase 3 trial was conducted across 79 centres in China. The study population comprised 531 patients aged 18 to 75 years with stage IIIB-IV squamous or non-squamous non-small-cell lung cancer (NSCLC). Eligible patients had no previous systemic treatment for advanced, recurrent, or metastatic disease, a PD-L1 tumour proportion score of 1% or greater, a life expectancy of at least 3 months, at least one measurable lesion, and an Eastern Cooperative Oncology Group performance status of 0 or 1. The trial was funded by the Chia Tai Tianqing Pharmaceutical Group.

The intervention group received intravenous benmelstobart at a dose of 1200 mg once on day 1, combined with oral anlotinib at 12 mg daily on days 1 through 14 of each cycle. The comparator group received intravenous pembrolizumab at 200 mg once on day 1, plus placebo administered every 3 weeks. Treatment cycles were repeated until disease progression or unacceptable toxicity.

The primary outcome was progression-free survival. At a median follow-up of 11.4 months (95% CI 9.4-13.1) for the benmelstobart plus anlotinib group and 10.6 months (9.0-13.0) for the pembrolizumab plus placebo group, the median progression-free survival was 11.0 months (95% CI 9.2-12.6) in the intervention group versus 7.1 months (95% CI 5.8-9.5) in the comparator group. The hazard ratio was 0.70 (95% CI 0.54-0.90) with a p-value of 0.0057, indicating a statistically significant improvement in progression-free survival for the benmelstobart plus anlotinib combination.

No secondary outcomes were reported in the provided data. Regarding safety, grade 3 or worse treatment-related adverse events occurred in 206 (59%) of 352 patients in the benmelstobart plus anlotinib group and 51 (29%) of 176 patients in the pembrolizumab plus placebo group. The most frequent grade 3 or worse adverse event was hypertension, observed in 90 (26%) patients in the intervention group versus five (3%) in the comparator group. Serious treatment-related adverse events occurred in 89 (25%) patients in the benmelstobart plus anlotinib group and 37 (21%) patients in the pembrolizumab plus placebo group. The most common serious adverse events included haemoptysis, which occurred in nine (3%) patients in the intervention group versus none in the comparator group, and immune-mediated pulmonary diseases, occurring in eight (2%) versus five (3%) patients, respectively. Discontinuations and specific tolerability metrics were not reported.

This study suggests benmelstobart plus anlotinib as a potential first-line option for driver gene-negative, PD-L1-positive, advanced NSCLC. However, the results should be interpreted with caution because longer-term follow-up is needed to establish effects on overall survival. The study design is observational regarding long-term efficacy endpoints, and the evidence is limited by the need for extended observation periods to confirm durability of benefit. Additionally, the safety profile highlights a higher incidence of hypertension and haemoptysis in the intervention group, which clinicians must monitor closely.

Key questions remain unanswered regarding the impact of this regimen on overall survival and long-term quality of life. The study was conducted exclusively in China, which may limit generalisability to other populations. Methodological limitations include the lack of reported discontinuation rates and the absence of data on specific tolerability metrics beyond adverse event frequencies. These gaps underscore the necessity for further research to fully characterize the risk-benefit profile of this combination therapy.

In summary, while the benmelstobart plus anlotinib combination shows promise for improving progression-free survival in this specific patient population, its role in clinical practice awaits confirmation of overall survival benefits and further safety data. Clinicians should consider these findings as preliminary evidence supporting a potential first-line strategy, pending additional long-term data.