Abstract
We performed a NCI-sponsored, prospective study of neoadjuvant FOLFIRINOX followed by chemoradiation with carboplatin/paclitaxel followed by surgery in patients with locally advanced gastric or gastroesophageal cancer. The primary objective was to determine completion rate of neoadjuvant FOLFIRINOX × 8 followed by chemoradiation. Secondary endpoints were toxicity and pathologic complete response (pCR) rate. Exploratory analysis was performed of circulating tumor DNA (ctDNA) to treatment response. From October 2017 to June 2018, 25 patients were enrolled. All patients started FOLFIRINOX, 92% completed all eight planned cycles, and 88% completed chemoradiation. Twenty (80%) patients underwent surgical resection, and 7 had a pCR (35% in resected cohort, 28% intention to treat). 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-chemoradiation ctDNA (P = 0.004) and/or postoperative ctDNA (P = 0.045) were associated with disease recurrence. Here we show neoadjuvant FOLFIRINOX followed by chemoradiation for locally advanced gastroesophageal cancer is feasible and yields a high rate of pCR. ctDNA appears to be a promising predictor of postoperative recurrence.See related commentary by Catenacci, p. 6281.
Highlights
Despite recent advancements, gastric and gastroesophageal junction adenocarcinoma (GEA) remains a lethal disease[1,2]
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
We show neoadjuvant FOLFIRINOX followed by CRT for locally advanced GEA is feasible and yields a high rate of pathologic complete response (pCR). circulating tumor DNA (ctDNA) appears to be a promising predictor of postoperative recurrence
Summary
Gastric and gastroesophageal junction adenocarcinoma (GEA) remains a lethal disease[1,2]. For locally advanced GEJ cancer, preoperative chemoradiation and perioperative chemotherapy have been established as standards of care[4,9] Despite these recent advancements, the risk of distant recurrence remains high, at over 50% by five years[3,5]. A multi-institutional phase II trial of 36 patients with locally advanced GEA evaluated pharmacogenomically dosed perioperative FOLFIRINOX and reported R0 resection rate of 92% and a pathologic complete response (pCR) rate of 23%17. Based on these promising results, we sought to perform a single-arm pilot study of total neoadjuvant therapy with FOLFIRINOX, followed by consolidative chemoradiation with concurrent carboplatin/paclitaxel, followed by surgery, in patients with GEA planned for curative intent therapy
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