The addition of serplulimab to chemotherapy significantly improved overall survival outcomes compared to chemotherapy alone in patients with previously untreated extensive-stage small cell lung cancer, according to phase 3 study results published in JAMA Oncology.
“Patients with SCLC usually present with extensive-stage disease at the time of diagnosis; the 5-year survival rate is only 7%,” wrote Ying Cheng, MD, medical oncologist at Jilin Cancer Hospital, China, and colleagues. “Since the 1990s, the standard first-line treatment for extensive-stage SCLC remained chemotherapy with a platinum-based agent plus etoposide, providing a median overall survival of approximately 10 months.”
Because the addition of PD-L1 inhibitors has shown a survival benefit when added to first-line chemotherapy, Cheng and colleagues sought to determine whether serplulimab, an anti-PD-L1 monoclonal antibody, would improve outcomes in combination with chemotherapy.
The researchers initiated the double-blind, phase 3 ASTRUM-005 clinical trial, which enrolled patients with extensive-stage SCLC and no previous exposure to systemic therapy. They randomly assigned patients to intravenous serplulimab (4.5 mg/kg every 3 weeks) or to placebo, with all patients receiving carboplatin and etoposide every 3 weeks for up to 4 cycles.
OS served as the study’s primary endpoint. Progression-free survival served as a secondary endpoint, and adverse events were observed. The study included data from 585 patients (serplulimab, n = 398; placebo, n = 196), who were recruited from 114 hospitals in six countries. The mean age of the cohort was 61.1 years (standard deviation, 8.67 years). At the time of reporting, 79.5% of patients (n = 465) had discontinued treatment, largely due to disease progression.
The median follow-up for all patients was 12.3 months (range, 0.2-24.8). Patients assigned to serplulimab achieved a median OS of 15.4 months (95% CI, 13.3-not reached), compared with 10.9 months (95% CI, 10-14.3) for patients assigned to placebo (HR = 0.63; 95% CI, 0.49-0.82; P < .001). The estimated 1-year survival rate (60.7% vs 47.8%) and 2-year survival rate (43.1% vs 7.9%) favored serplulimab.
The median PFS by independent assessment also favored assignment to serplulimab (5.7 months vs 4.3 months; HR = 0.48; 95% CI, 0.38-0.59). The median investigator-assessed PFS for patients assigned to serplulimab was 5.5 months, compared to 4.3 months in the placebo group (HR = 0.58; 95% CI, 0.48–0.71). Serplulimab was associated with an objective response rate of 80.2% (95% CI, 75.9-84.1), compared with 70.4% (95% CI, 63.5-76.7) for placebo. The median durations of response were 5.6 months and 3.2 months, respectively. Assignment to serplulimab correlated with favorable outcomes for patients with brain metastases (median OS, 13.9 months vs 10 months) and patients without brain metastases (15.6 months vs 11.3 months).
“There seemed to be an imbalance in median OS for patients with a tumor proportion score of less than 1% for PD-L1 expression level (15 months in the serplulimab group compared with 10.5 months in the placebo group; HR = 0.58; 95% CI, 0.44-0.76) and for patients with a tumor proportion score of 1% or greater (not reached vs 12.9 months, respectively; HR = 0.92; 95% CI, 0.44-1.89),” wrote the researchers. “However, the post hoc test for interaction did not show significant interactions between the subgroup factors and treatment group.”
In total, 95.6% of patients assigned to serplulimab and 97.4% of patients assigned to placebo experienced treatment-emergent adverse events. The rates of grade 3 or higher treatment-emergent adverse events were 82.5% and 80.1%, respectively.
Grade 3 or higher treatment-related adverse events occurred in 33.2% (n = 129) of the serplulimab cohort and 27.6% (n = 54) of the placebo cohort, the most common of which were decreased neutrophil count (14.1% vs 13.8%), decreased white blood cell count (8.5% vs 8.7%), decreased platelet count (6.2% vs 8.2%), and anemia (5.4% vs 5.6%).
Thirty patients assigned to serplulimab and 20 patients assigned to placebo died due to treatment-emergent adverse events. Three patients in the serplulimab arm died of adverse events related to the study product, including acute coronary syndrome, pyrexia, and decreased platelet count. One death in the placebo arm (due to thrombocytopenia) was attributed to treatment.
The researchers acknowledged limitations of their study, including the lack of a head-to-head comparison between serplulimab and another PD-L1 inhibitor and the relatively small number of patients with brain metastases. They also noted that carboplatin was the only platinum-based chemotherapy included in the trial, which may not reflect treatment in the real-world setting.
“Among patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population,” they concluded.
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Disclosures: Some authors declared financial ties to drugmakers. See full study for details.
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