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CALGB 80803: PET-Directed Therapy After Induction Chemotherapy Yields Promising 5-Year Overall Survival in Patients with Esophageal Cancer

2021 Year in Review - Gastrointestinal Cancer

The use of PET to direct therapy after nonresponse to induction chemotherapy improved overall survival in patients with resectable esophageal cancer.

Resectable esophageal cancer has several neoadjuvant and adjuvant treatments, including chemotherapy, radiotherapy, and chemoradiotherapy, but the optimal sequence and combinations of these therapies are unsettled. Further complicating the matter, concurrent use of chemotherapy with neoadjuvant chemoradiation makes discerning the efficacy of chemotherapy difficult. The CALGB 80803 (Alliance) trial evaluated the use of positron emission tomography (PET) scan imaging to assess the response in patients with esophageal and esophagogastric junction (EGJ) adenocarcinoma who received induction chemotherapy to direct further therapy to attempt to improve response and survival outcomes among those patients who were PET nonresponders.

In this interventional, randomized phase 2 study, 241 patients with esophageal or EGJ adenocarcinoma were enrolled to undergo PET-directed therapy after induction chemotherapy. After baseline PET was performed, patients were randomized into 2 treatment groups. For induction chemotherapy, one group received modified oxaliplatin, leucovorin, and fluorouracil (mFOLFOX) and the second group received carboplatin and paclitaxel (CP). After induction, the PET was repeated to assess the change in maximum standardized uptake value (SUV) from baseline value. If the patient was found to be a nonresponder (defined as <35% decrease in SUV), they were crossed over into the alternative chemotherapy during chemoradiation while PET responders remained on the same chemotherapy during chemoradiation (50.4 Gy/28 fractions). Surgery was performed 6 weeks after chemoradiation. The study’s primary end point was the pathologic complete response in the nonresponding patients after they switched chemotherapy regimens.

In the 39 nonresponding patients who received induction FOLFOX chemotherapy and crossed over to CP chemotherapy, the pathologic complete response was 18.0%. There were 50 patients who received CP as induction chemotherapy and did not respond. They were switched to FOLFOX and had a 20% pathologic response. When the responders were evaluated, those who received induction FOLFOX had a 40.3% pathologic complete response rate, whereas those who received induction CP had a 14.1% response rate. The CALGB 80803 clinical trial has a 5.2-year median follow-up period. For PET responders, the median overall survival (OS) was 48.4 months versus 27.4 months for those patients who were nonresponsive to treatment. Patients who received FOLFOX for induction chemotherapy and continued on FOLFOX therapy during chemoradiation and who were PET responders had a 5-year OS of 53%. Pathologic complete response rate improvement in PET nonresponders was achieved in this study.

PET-directed therapy after nonresponse to induction chemotherapy improves OS in patients with resectable esophageal cancer.

Source: Goodman KA, Ou FS, Hall NC, et al. Randomized phase 2 study of PET response-adapted combined modality therapy for esophageal cancer: mature results of the CALGB 80803 (Alliance) trial. J Clin Oncol. 2021;39:2803-2815.