Survival outcomes from CALGB 80803 (Alliance): A randomized phase II trial of PET scan-directed combined modality therapy for esophageal cancer.

Abstract

4012 Background: We evaluated use of early PET response after induction chemotherapy (CT) to direct changing to alternative CT during preoperative chemoradiation (CRT) among patients (pts) with resectable esophageal and gastroesophageal junction (GEJ) adenocarcinomas who are PET nonresponders. We previously reported the primary endpoint of improving pathologic complete response (pCR) in PET nonresponders; pre-specified efficacy criteria were met for improvement in pCR rates with changing CT during CRT. We now report survival outcomes by PET response status. Methods: 257 pts enrolled, underwent baseline PET and were randomized to 1 of 2 induction CT arms: modified FOLFOX-6 (oxaliplatin, leucovorin, 5-FU) days 1, 15, 29 or carboplatin/paclitaxel (CP) days 1, 8, 22, 29. Repeat PET was performed days 36-42; change in maximum standardized uptake value (SUV) from baseline was assessed. PET nonresponders ( < 35% decrease in SUV: PET-NR) crossed over to alternative CT regimen during CRT (50.4 Gy/28 fractions). PET responders (≥35% decrease in SUV: PET-R) continued on same CT during CRT. Pts underwent surgery at 6 weeks post-CRT. Overall survival (OS) was measured from randomization to death from any cause; 2-year (yr) OS rates were estimated using the Kaplan-Meier method. Results: 240 eligible pts received protocol treatment and 222 had an evaluable repeat PET. With median follow-up of 35.9 months (mo) (95% CI: 33.1-41.2), median OS was 34.4 mo (95%CI: 28.4-49.7) and 2-yr OS was 61.8% (95%CI: 55.7-68.5%). Median OS for PET-R was 40.2 mo (95% CI:31.0, not estimable [NE]) and for PET-NR was 27.4 mo (95% CI: 20.3, NE). Median and 2-yr OS by induction CT and PET response appear below. Clinical trial information: NCT01333033. Conclusions: PET response after induction CT is prognostic for outcome in pts with esophageal and GEJ adenocarcinomas. Outcomes for PET-R pts receiving induction and concurrent FOLFOX are encouraging. Support: U10CA180821, U10CA180882 Response Group Events/N Median OS (mo) 95% CI (mo) 2-yr OS (%) 95% CI (%) CP N = 111 PET-R 31/63 31.0 (20.4, NE) 57.4 (46.2, 71.3) PET-NR 28/48 26.4 (16.0, NE) 52.4 (39.8, 69.0) FOLFOX N = 111 PET-R 29/72 48.7 (33.1, NE) 73.3 (63.4, 84.7) PET-NR 20/39 30.9 (25.4, NE) 64.0 (50.0. 82.0)