Checkpoint inhibitor (CPI) therapy revolutionized treatment for advanced non-small cell lung cancer (NSCLC); however, most patients progress due to primary or acquired resistance. Sitravatinib is a receptor tyrosine kinase inhibitor that can shift the immunosuppressive tumor microenvironment towards an immunostimulatory state. Combining sitravatinib with nivolumab (sitra+nivo) may potentially overcome initial CPI resistance.
In the phase III SAPPHIRE study, patients with advanced non-oncogenic driven, non-squamous NSCLC who initially benefited from (≥4 months on CPI without progression) and subsequently experienced disease progression on or after CPI combined with or following platinum-based chemotherapy were randomized 1:1 to sitra (100 mg once daily orally)+nivo (240 mg every 2 weeks or 480 mg every 4 weeks intravenous) or docetaxel (75 mg/m every 3 weeks intravenous).
overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR; all assessed by blinded independent central review), and safety.
A total of 577 patients were randomized: sitra+nivo, n = 284; docetaxel, n = 293 (median follow-up, 17.1 months). Sitra+nivo did not significantly improve OS versus docetaxel (median, 12.2 versus 10.6 months; hazard ratio [HR] 0.86; 95% confidence interval [CI] 0.70-1.05; p = 0.144). Median PFS was 4.4 versus 5.4 months, respectively (HR 1.08; 95% CI 0.89-1.32; p = 0.452). ORR was 15.6%, sitra+nivo and 17.2%, docetaxel (p = 0.597); CBR was 75.5% and 64.5%, respectively (p = 0.004); median DOR was 7.4 versus 7.1 months, respectively (p = 0.924). Grade ≥3 treatment-related adverse events were observed in 53.0% versus 66.7% of patients receiving sitra+nivo versus docetaxel, respectively.
Although median OS was numerically longer with sitra+nivo, the primary endpoint was not met in patients with previously treated advanced non-squamous NSCLC. The safety profiles demonstrated were consistent with previous reports.
Copyright © 2023. Published by Elsevier Ltd.
