The combination of serplulimab and chemotherapy prolongs overall survival (OS), compared with chemotherapy alone, in patients with previously untreated, extensive-stage small cell lung cancer (ES-SCLC), according to phase 3 results published in JAMA.
“To our knowledge, this is the first phase 3 trial demonstrating OS benefits of a PD-1 inhibitor in combination with chemotherapy as a first-line treatment for patients with ES-SCLC,” the study authors wrote.
The trial (ASTRUM-005; ClinicalTrials.gov Identifier: NCT04063163) included 585 randomized patients with treatment-naïve ES-SCLC. In the overall population, the mean age at baseline was 61.1 years, and 17.8% of patients were women. Baseline characteristics were well balanced between the treatment arms.
Patients were randomly assigned 2:1 to receive serplulimab plus chemotherapy (n=389) or placebo plus chemotherapy (n=196). For chemotherapy, all patients received etoposide at 100 mg/m2 on days 1-3 and carboplatin within the area under the serum drug concentration time curve of 5 mg/mL/min (up to 750 mg) on day 1 of each cycle for up to 4 cycles.
Patients received serplulimab at 4.5 mg/kg every 3 weeks until disease progression, death, unacceptable toxicity, consent withdrawal, or other reasons specified in the trial protocol. Patients could continue receiving their assigned treatment after disease progression at the investigators’ discretion.
Overall, 79.5% of patients in the serplulimab arm and 88.3% in the placebo arm discontinued study treatment. The most common reason for discontinuation was disease progression.
The primary endpoint of this study was OS, and the median follow-up was 12.3 months. The median OS was significantly longer in the serplulimab arm than in the placebo arm — 15.4 months and 10.9 months, respectively (hazard ratio [HR], 0.63; 95% CI, 0.49-0.82; P <.001).
The 1-year OS rate was 60.7% in the serplulimab arm and 47.8% in the placebo arm. The 2-year OS rate was 43.1% and 7.9%, respectively.
The median progression-free survival was 5.7 months in the serplulimab arm and 4.3 months in the placebo arm (HR, 0.48; 95% CI, 0.38-0.59).
The objective response rate was 80.2% in the serplulimab arm and 70.4% in the placebo arm. The median duration of response was 5.6 months and 3.2 months, respectively.
Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 33.2% of patients in the serplulimab arm and 27.6% of those in the placebo arm.
The most common grade 3 or higher TRAEs (in the serplulimab and placebo arms, respectively) were decreased neutrophil count (14.1% and 13.8%), decreased white blood cell count (8.5% and 8.7%), decreased platelet count (6.2% and 8.2%), and anemia (5.4% and 5.6%).
The study authors concluded that these results support “the use of serplulimab plus chemotherapy as the first-line treatment for this patient population.”
Disclosures: This study was supported by Shanghai Henlius Biotech, Inc. Some of the study authors are employed by the company. Please see the original reference for a full list of disclosures.
Cheng Y, Han L, Wu L, et al. Effect of first-line serplulimab vs placebo added to chemotherapy on survival in patients with extensive-stage small cell lung cancer. The ASTRUM-005 randomized clinical trial. JAMA. Published online September 27, 2022. doi:10.1001/jama.2022.16464