First-Line Serplulimab Prolongs Survival in Advanced NSCLC

Adding serplulimab to first-line chemotherapy improved survival outcomes in a phase 3 trial of patients with advanced non-small cell lung cancer (NSCLC). These results, from the ASTRUM-004 trial, were published in Cancer Cell.

The ASTRUM-004 trial (ClinicalTrials.gov identifier: NCT04033354) included 537 patients with stage IIIB/C or IV squamous cell NSCLC who did not have targetable gene alterations.

The patients were randomly assigned to receive serplulimab plus nab-paclitaxel and carboplatin (n=358) or placebo plus nab-paclitaxel and carboplatin (n=179). Baseline characteristics were well balanced between the arms.

Patients received chemotherapy, with or without serplulimab, for 4 to 6 cycles. This was followed by serplulimab or placebo maintenance for up to 2 years. Patients in the chemotherapy-alone arm could cross over to receive serplulimab alone after disease progression.

The median follow-up was 16.9 months at the second interim analysis. At that time, none of the patients had completed study treatment, and 76.9% had discontinued treatment. The most common reasons for discontinuation were progressive disease (40.8%), adverse events (12.3%), patient decision (8.6%), and death (8.0%).

By the second interim analysis, 84 patients (46.9%) in the chemotherapy-alone arm had crossed over to receive serplulimab monotherapy, and 65 patients (18.2%) in the serplulimab-chemotherapy arm continued serplulimab treatment beyond disease progression.

The median progression-free survival (PFS) by independent review was significantly longer in the serplulimab-chemotherapy arm than in the chemotherapy-alone arm — 8.3 months and 5.7 months, respectively (hazard ratio [HR], 0.53; 95% CI, 0.42-0.67).

The 12-month PFS rate was 40.2% in the serplulimab-chemotherapy arm and 9.9% in the chemotherapy-alone arm. The 18-month PFS rate was 28.7% and 6.6%, respectively.

An analysis of the effects of crossover revealed that the median PFS was 8.3 months in patients treated with serplulimab-chemotherapy, 5.7 months in patients who crossed over from the chemotherapy arm to receive serplulimab monotherapy, and 5.7 months in patients who received chemotherapy alone.

The median overall survival (OS) at the second interim analysis was 21.9 months in the serplulimab-chemotherapy arm and 17.3 months in the chemotherapy-alone arm (HR, 0.74; 95% CI, 0.56–0.98; P =.036). The 24-month OS rate was 44.4% and 28.2%, respectively.

An analysis of the effects of crossover revealed that the median OS was 21.9 months in patients who received serplulimab and chemotherapy, 21.7 months in those who crossed over to receive serplulimab monotherapy, and 10.7 months in patients who received chemotherapy alone. When compared to patients who received only chemotherapy, patients who received serplulimab and chemotherapy had a significant reduction in the risk of death (HR, 0.51; 95% CI, 0.36-0.72).

At the final OS analysis, the median follow-up was 31.1 months. The median OS was 22.7 months in the serplulimab-chemotherapy arm and 18.2 months in the chemotherapy-alone arm (HR, 0.73; 95% CI 0.58-0.93; P =.010). The 24-month OS rate was 47.4% and 34.4%, respectively.

The rate of treatment-related adverse events (TRAEs) was 72.1% in the serplulimab-chemotherapy arm and 63.7% in the chemotherapy-alone arm. The rate of grade 3 or higher TRAEs was 35.2% and 32.4%, respectively. There were 5 fatal TRAEs in the serplulimab-chemotherapy arm and 2 in the chemotherapy-alone arm.

The most common grade 3 or higher TRAEs (in the serplulimab and chemotherapy-alone arms, respectively) were neutrophil count decrease (14.8% vs 14.5%), anemia (12.0% vs 10.6%), and white blood cell count decrease (10.1% vs 11.2%).

“With similar efficacy and safety profile to those of pembrolizumab plus chemotherapy shown in the KEYNOTE-407 study, serplulimab plus chemotherapy represents another treatment option for first-line patients with locally advanced or metastatic advanced squamous NSCLC,” the researchers concluded.

Disclosures: This study was supported by Shanghai Henlius Biotech, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor