Outcomes of Patients with Rare Cancers Treated with Combination Immune Checkpoint Inhibitors With and Without Prior...

There are limited data on response and survival outcomes for patients who receive the combination of anti-PD-1 and anti-CLTA-4 after prior failure of an anti-PD-1/L1, in particular among patients with less common cancers. We analyzed a unique trial resource, an NCI-sponsored basket trial for participants with rare solid tumors conducted by SWOG that was open at over 1,000 sites across the USA (S1609/DART). Participants received Ipilimumab (1mg/kg every six weeks) plus nivolumab (240 mg every two weeks) (both intravenously). The trial eligibility allowed prior exposure to anti-PD-1/L1, and our objective was to compare response and survival outcomes for patients with and without prior anti-PD-1/PDL-1.

Logistic and Cox regression models were used to evaluate associations between prior anti-PD-1/PDL-1 exposure and the endpoints of clinical benefit rate (CBR) (includes stable disease of at least six months and objective response by RECISTv1.1), progression-free survival (PFS), and overall survival (OS).

CBR was not significantly different between those with and without prior anti-PD-1/L1 exposure, 26% in both groups. There were no significant differences in PFS and OS between patients with and without prior anti-PD-1/L1 exposure on either univariate and multivariable analysis (multivariable hazard ratio, 95% confidence interval and p-value: PFS: 1.18, 0.83-1.68, p=0.36; OS: 1.11, 0.76-1.63, p=0.58).

There were no statistically or clinically significant differences in outcomes with and without prior anti-PD-1/L1 exposure for patients with a variety of rare cancers treated with nivolumab and ipilimumab. Patients with prior anti-PD-1/L1 exposure should be eligible for clinical trials evaluating combination immunotherapy.