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Addition of Adebrelimab to Carboplatin/Etoposide in First-Line Treatment of Extensive-Stage SCLC


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In a Chinese phase III trial (CAPSTONE-1) reported in The Lancet Oncology, Jie Wang, MD, PhD, and colleagues found that the addition of adebrelimab, a novel anti–PD-L1 antibody, to carboplatin and etoposide significantly improved overall survival as a first-line treatment for patients with extensive-stage small cell lung cancer (SCLC).

Jie Wang, MD, PhD

Jie Wang, MD, PhD

Study Details

The multicenter, double-blind trial included 462 patients who were randomly assigned between December 2018 and September 2020. They received four to six 21-day cycles of carboplatin area under the curve = 5 mg/mL/min on day 1 of each cycle and etoposide at 100 mg/m² on days 1 to 3 of each cycle, with either adebrelimab at 20 mg/kg (n = 230) or placebo (n = 232) on day 1 of each cycle, followed by maintenance therapy with adebrelimab or placebo. Overall, 85% to 86% of patients had a PD-L1 tumor proportion score of < 1%. The primary endpoint was overall survival.

Overall Survival

At data cutoff (in October 2021), median follow-up was 13.5 months (interquartile range = 8.9–20.1 months). Median overall survival was 15.3 months (95% confidence interval [CI] = 13.2–17.5 months) in the adebrelimab group vs 12.8 months (95% CI = 11.3–13.7 months) in the control group (hazard ratio [HR] = 0.72, 95% CI = 0.58–0.90, P = .0017). Rates at 12 and 24 months were 62.9% vs 52.0% and 31.3% vs 17.2%. 

Progression-free survival as assessed by blinded independent review committee was significantly prolonged in the adebrelimab group (HR = 0.67, 95% CI = 0.54–0.83, P < .0001). Median progression-free survival was 5.8 months (95% CI = 5.6–6.9 months) vs 5.6 months (95% CI = 5.5–5.7 months), with rates at 6 and 12 months of 49.4% vs 37.3% and 19.7% vs 5.9%.  Among 213 vs 229 patients who discontinued study treatment, 59% vs 70% received at least one subsequent systemic anticancer therapy.

KEY POINTS

  • The addition of adebrelimab to carboplatin/etoposide prolonged overall survival.
  • Median overall survival was 15.3 vs 12.8 months.

Adverse Events

Grade ≥ 3 treatment-related adverse events occurred in 86% of patients in the adebrelimab group vs 85% of the control group, the most common being decreased neutrophil count (76% vs 75%), decreased white blood cell count (46% vs 38%), decreased platelet count (38% vs 34%), and anemia (28% vs 28%). Treatment-related serious adverse events occurred in 39% vs 28% of patients. Immune-mediated adverse events of any grade occurred in 28% vs 17%, with the most common in the adebrelimab group being hypothyroidism (9%) and hepatic laboratory abnormalities (7%). Four treatment-related deaths were reported, including two in the adebrelimab group (due to respiratory failure and interstitial lung disease/pneumonia) and two in the control group (due to multiple organ dysfunction and unknown cause).

The investigators concluded, “Adding adebrelimab to chemotherapy significantly improved overall survival with an acceptable safety profile in patients with extensive stage SCLC, supporting this combination as a new first-line treatment option for this population.”

Ying Cheng, MD, of the Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Jiangsu Hengrui Pharmaceuticals. For full disclosures of the study authors, visit thelancet.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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