Impact of prior chemotherapy on progression-free survival in patients (pts) with advanced pancreatic neuroendocrine tumors (pNET): Results from the RADIANT-3 trial

Background: In the phase III RADIANT-3 trial, everolimus (EVE), an oral mTOR inhibitor, demonstrated superior progression-free survival (PFS) with a median of 11.0 vs 4.6 mo for placebo (PBO) (HR=0.35; 95% confidence interval, 0.27-0.45; P<0.0001) in pts with advanced pNET (ESMO 2010, Abstract #LBA9). An exploratory analysis of prior chemotherapy use and PFS from the RADIANT-3 trial is presented. Methods: Pts with progressive advanced low- or intermediate-grade pNET were randomized to EVE 10 mg/d orally (n=207) or PBO (n=203); both arms received best supportive care. The primary endpoint was PFS per central review (RECIST v1.0). Pts were stratified by use of prior vs no prior chemotherapy. Results: Overall, 206/410 (50%) pts received prior chemotherapy. Prior chemotherapy use was balanced in both arms: 104/207 (50%) EVE pts vs 102/203 (49%) PBO pts. No difference was observed in baseline characteristics (age, sex, race, tumor type, histologic grade) and baseline tumor biomarker levels for pts receiving prior chemotherapy vs those without. Time since initial diagnosis was >2 years for 147 (71%) pts with prior chemotherapy vs 98 (48%) pts without prior chemotherapy. A higher proportion of pts with prior chemotherapy also had received prior somatostatin therapy (54% prior chemotherapy vs 45% no prior chemotherapy). A positive treatment effect with EVE was observed in pts both with and without prior chemotherapy. EVE significantly prolonged PFS vs placebo in pts with prior chemotherapy (HR=0.34; P<0.0001) and those without prior chemotherapy (HR=0.42; P<0.001). Median PFS with EVE for pts with prior chemotherapy was 11.0 mo vs 11.4 mo for those without prior chemotherapy (HR=1.120; 95% CI, 0.768-1.634; P=0.56). Median PFS with PBO for pts with prior chemotherapy was 3.2 mo vs 5.4 mo for those without prior chemotherapy (HR=1.3; 95% CI, 0.990-1.828; P=0.054). Conclusions: EVE demonstrated significantly longer median PFS than PBO in pts with advanced pNET, regardless of prior chemotherapy use. These results suggest that EVE should be considered a treatment option for pNET pts, including those without prior chemotherapy.