In a Chinese phase III trial (CAMPASS) reported in The Lancet Oncology, Zhong et al found that the PD-L1 inhibitor benmelstobart plus the tyrosine kinase inhibitor anlotinib significantly improved progression-free survival vs placebo plus pembrolizumab in the first-line treatment of PD-L1–positive driver gene–negative advanced non–small cell lung cancer (NSCLC).
Study Details
In the single-blind multicenter trial, 531 patients with stage IIIB to IV squamous or nonsquamous NSCLC and a PD-L1 tumor proportion score of 1% or greater were randomly assigned 2:1 between August 2021 and December 2022 to receive benmelstobart plus anlotinib (n = 354) or placebo plus pembrolizumab (n = 177). Treatments consisted of benmelstobart at 1,200 mg on day 1 plus anlotinib at 12 mg daily on days 1 to 14, or pembrolizumab at 200 mg plus placebo on day 1 every 3 weeks. Treatment continued until disease progression or unacceptable toxicity, with treatment beyond progression being permitted if continued clinical benefit was observed. Exposure to benmelstobart and pembrolizumab could not exceed 2 years. The primary endpoint was progression-free survival on blinded independent review committee assessment.
Key Findings
Median follow-up was 11.4 months (95% confidence interval [CI] = 9.4–13.1 months) in the combination group vs 10.6 months (95% CI = 9.0–13.0 months) in the pembrolizumab group. Median progression-free survival was 11.0 months (95% CI = 9.2–12.6 months) in the combination group vs 7.1 months (95% CI = 5.8–9.5 months) in the pembrolizumab group (hazard ratio = 0.70, 95% CI = 0.54–0.90, P = .0057). Rates at 6 and 2 months were 75% vs 57% and 46% vs 36%, respectively.
Grade 3 or higher treatment-related adverse events occurred in 59% of patients in the benmelstobart plus anlotinib group (most commonly hypertension [26%]) vs 29% of the pembrolizumab group. Serious treatment-related adverse events occurred in 25% vs 21% of patients. Treatment-related death occurred in five patients in the benmelstobart plus anlotinib group (due to hemoptysis in two patients and immune-mediated pulmonary disease, disease progression, and pneumonia in one each) and in four patients in the pembrolizumab group (due to respiratory failure, pulmonary inflammation, disease progression, and myocardial injury in one each).
The investigators concluded: “Benmelstobart plus anlotinib showed longer progression-free survival than pembrolizumab plus placebo, and no unexpected safety signals were reported, suggesting benmelstobart plus anlotinib as a potential first-line option in driver gene–negative, PD-L1–positive, advanced NSCLC. Longer term follow-up is needed to establish effects on overall survival.”
Baohui Han, MD, of Shanghai Jiao Tong University School of Medicine, Shanghai, China and Kai Li, MD, of Tianjin Medical University Cancer Institute and Hospital, Tianjin, China are the corresponding authors for The Lancet Oncology article.
DISCLOSURE: The study was funded by Chia Tai Tianqing Pharmaceutical Group. For full disclosures of the study authors, visit thelancet.com.
