Sintilimab ( Tyvyt ), an anti–programmed death 1 antibody, plus Pemetrexed and Platinum had revealed promising efficacy for nonsquamous non-small-cell lung cancer ( NSCLC ) in a phase 1b study.
Researchers have conducted a randomized, double-blind, phase 3 study to compare the efficacy and safety of Sintilimab with placebo, both in combination with such chemotherapy.
A total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC without sensitizing EGFR or anaplastic lymphoma kinase ( ALK ) genomic aberration were randomized ( 2:1 ratio ) to receive either Sintilimab 200 mg or placebo plus Pemetrexed and Platinum once every 3 weeks for four cycles, followed by Sintilimab or placebo plus Pemetrexed therapy.
Crossover or treatment beyond disease progression was allowed.
The primary end point was progression-free survival ( PFS ) as judged by an independent radiographic review committee.
As of November 15, 2019, the median follow-up was 8.9 months.
The median progression-free survival was significantly longer in the Sintilimab-combination group than that in the placebo-combination group ( 8.9 versus 5.0 months; hazard ratio, HR 0.482, 95% confidence interval [ CI ]: 0.362–0.643; p less than 0.00001 ).
The confirmed objective response rate ( ORR ) was 51.9% ( 95% CI: 45.7%–58.0% ) in the Sintilimab-combination group and 29.8% ( 95% CI: 22.1%–38.4% ) in placebo-combination group.
The incidence of grade 3 or higher adverse events was 61.7% in Sintilimab-combination group and 58.8% in placebo-combination group.
In conclusion, in Chinese patients with previously untreated, locally advanced or metastatic nonsquamous non-small-cell lung cancer, the addition of Sintilimab to chemotherapy with Pemetrexed and Platinum resulted in considerably longer progression-free survival than with chemotherapy alone with manageable safety profiles. ( Xagena )
Yang Y et al, J Thorac Oncol 2020;15: 1636-1646