Sitravatinib plus nivolumab slightly better than docetaxel in advanced NSCLC

Treatment with sitravatinib plus nivolumab (sitra + nivo) results in numerically longer median overall survival (OS), albeit statistically nonsignificant, in patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC) compared with docetaxel, a study has shown.

“Sitravatinib is a receptor tyrosine kinase inhibitor that can shift the immunosuppressive tumour microenvironment toward an immunostimulatory state,” the investigators said. “Combining sitravatinib with nivolumab may potentially overcome initial checkpoint inhibitor (CPI) resistance.”

The phase III SAPPHIRE study examined the efficacy of this combination in patients with advanced nononcogenic driven, nonsquamous NSCLC who were initially treated with (≥4 months on CPI without progression) and subsequently experienced disease progression on or after CPI combined with or following platinum-based chemotherapy.

A total of 577 patients were randomized 1:1 to sitra (n=284; 100 mg once daily administered orally) + nivo (240 mg every 2 weeks or 480 mg every 4 weeks administered intravenously) or docetaxel (n=293; 75 mg/m² every 3 weeks administered intravenously).

OS was the primary endpoint, and secondary ones 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. The median follow-up was 17.1 months.

Sitra + nivo improved OS but fell short of achieving statistical significance when compared with docetaxel (median, 12.2 vs 10.6 months; hazard ratio [HR], 0.86, 95 percent confidence interval [CI], 0.70‒1.05; p=0.144).

For the secondary outcomes, the median PFS with sitra + nivo compared with docetaxel was 4.4 versus 5.4 months (HR, 1.08, 95 percent CI, 0.89‒1.32; p=0.452). The ORR was 15.6 percent and 17.2 percent (p=0.597), while the CBR was 75.5 percent and 64.5 percent, respectively (p=0.004). The corresponding median DOR was 7.4 versus 7.1 months (p=0.924).

Grade ≥3 treatment-related adverse events occurred in 53.0 percent of patients treated with sitra + nivo and 66.7 percent of those who received docetaxel. “The safety profiles demonstrated were consistent with previous reports,” the investigators said.

“CPI therapy revolutionized treatment for advanced NSCLC; however, most patients progress due to primary or acquired resistance,” the investigators noted.