In the Chinese phase III GEMSTONE-302 trial reported in The Lancet Oncology, Caicun Zhou, MD, and colleagues found that the addition of the PD-L1 inhibitor sugemalimab to platinum-based chemotherapy improved progression-free survival in the first-line treatment of metastatic squamous or nonsquamous non–small cell lung cancer (NSCLC).
Caicun Zhou, MD
Study Details
In the multicenter double-blind trial, 479 patients were randomly assigned 2:1 between December 2018 and May 2020 to receive sugemalimab (n = 320) or placebo (n = 159) in combination with chemotherapy. Treatment consisted of sugemalimab at 1,200 mg or placebo every 3 weeks plus carboplatin at AUC 5 and paclitaxel at 175 mg/m² for squamous NSCLC (129 vs 63 patients), or carboplatin at AUC 5 and pemetrexed at 500 mg/m² for nonsquamous NSCLC (191 vs 96 patients). Chemotherapy was given for up to four cycles, followed by maintenance sugemalimab or placebo in patients with squamous NSCLC and sugemalimab at 500 mg/m² or placebo plus pemetrexed for nonsquamous NSCLC.
The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population.
Progression-Free Survival
At a preplanned interim analysis (data cutoff in June 2020), median follow-up was 8.6 months (interquartile range [IQR] = 6.1–11.4 months). Median progression-free survival was 7.8 months (95% confidence interval [CI] = 6.9–9.0 months) in the sugemalimab group vs 4.9 months (95% CI = 4.7–5.0 months) in the control group (stratified hazard ratio [HR] = 0.50, 95% CI = 0.39–0.64, P < .0001). At the final analysis (data cutoff in March 2021), median follow-up was 17.8 months (IQR = 15.1–20.9 months). Median progression-free survival was 9.0 months (95% CI = 7.4–10.8 months) in the sugemalimab group vs 4.9 months (95% CI= 4.8–5.1 months) in the control group (stratified HR = 0.48, 95% CI = 0.39–0.60, P < .0001).
At final progression-free survival analysis, median progression-free survival was 8.3 months (95% CI = 6.9–10.9 months) vs 4.8 months (95% CI = 4.2–4.9 months) among patients with squamous disease (HR = 0.34, 95% CI = 0.24–0.48) and 9.6 months (95% CI = 8.3–11.0 months) vs 5.9 months (95% CI = 4.9-7.1 months) among those with nonsquamous disease (HR = 0.59, 95% CI = 0.45–0.79). Hazard ratios ranged from 0.41 to 0.56 according to PD-L1 expression < 1% (40% of study population), ≥ 1% (60% of population), 1% to 49%, and ≥ 50%.
Overall survival data were not mature for formal analysis. On preliminary analysis, median overall survival was 22.8 months (95% CI = 19.7 months–not reached) in the sugemalimab group vs 17.7 months (95% CI = 12.8–20.8 months) in the control group (stratified HR = 0.67, 95% CI = 0.50–0.90, P = .0064).
KEY POINTS
- The addition of sugemalimab to platinum-based chemotherapy significantly improved progression-free survival in patients with squamous or nonsquamous metastatic NSCLC.
- Median progression-free survival was 9.0 vs 4.9 months among all patients, including 8.3 vs 4.8 months among patients with squamous disease and 9.6 vs 5.9 months among those with nonsquamous disease.
Adverse Events
Treatment-related grade 3 or 4 adverse events occurred in 54% of patients in the sugemalimab group and 56% of patients in the control group—most commonly, decreased neutrophil count (33% vs 33%), decreased white blood cell count (14% vs 17%), anemia (13% vs 11%), and decreased platelet count (10% vs 9%). Immune-related adverse events occurred in 25% of the sugemalimab group, most commonly hypothyroidism (11%).
Treatment-related serious adverse events occurred in 23% vs 20% of patients. Treatment-related death occurred in 10 patients (3%) in the sugemalimab group (pneumonia in 2; unspecified cause in 2; and pneumonia with respiratory failure, myelosuppression with septic shock, respiratory failure, abdominal pain, cardiac failure, and immune-mediated pneumonitis in 1 each) and in 2 patients (1%) in the control group (pneumonia and multiple organ dysfunction syndrome, respectively).
The investigators concluded, “Sugemalimab plus chemotherapy showed a statistically significant and clinically meaningful progression-free survival improvement compared with placebo plus chemotherapy in patients with previously untreated squamous and nonsquamous metastatic NSCLC, regardless of PD-L1 expression, and could be a new first-line treatment option for both squamous and nonsquamous metastatic NSCLC.”
Dr. Zhou, of Shanghai Pulmonary Hospital, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by CStone Pharmaceuticals. For full disclosures of the study authors, visit thelancet.com.
