Results and molecular correlates from a pilot study of neoadjuvant induction FOLFIRINOX followed by chemoradiation and surgery for gastroesophageal adenocarcinomas.

PURPOSE: We performed a NCI-sponsored, prospective study of neoadjuvant FOLFIRINOX followed by chemoradiation (CRT) with carboplatin/paclitaxel followed by surgery in patients with locally advanced gastric or gastroesophageal (GEA) cancer.

EXPERIMENTAL DESIGN: The primary objective was to determine completion rate of neoadjuvant FOLFIRINOX x 8 followed by CRT. Secondary endpoints were toxicity and pathologic complete response (pCR) rate. Exploratory analysis was performed of ctDNA to treatment response.

RESULTS: From Oct 2017 to June 2018, 25 patients were enrolled. All patients started FOLFIRINOX, 92% completed all 8 planned cycles, and 88% completed CRT. Twenty (80%) patients underwent surgical resection, and 7 had a pCR (35% in resected cohort, 28% ITT ). Tumor-specific mutations were identified in 21 (84%) patients, of whom 4 and 17 patients had undetectable and detectable ctDNA at baseline, respectively. Presence of detectable post-CRT ctDNA (p=0.004) and/or postoperative ctDNA (p=0.045) were associated with disease recurrence.

CONCLUSIONS: Here we show neoadjuvant FOLFIRINOX followed by CRT for locally advanced GEA is feasible and yields a high rate of pCR. ctDNA appears to be a promising predictor of postoperative recurrence.