Induction versus no induction chemotherapy before neoadjuvant chemoradiotherapy and surgery in oesophageal adenocarcinoma: a multicentre randomised phase II trial (NCCTG N0849 [Alliance]). (June 2021)

• Record Type: Journal Article
• Authors: Yoon, Harry H.; Ou, Fang-Shu; Soori, Gamini S.; Shi, Qian; Wigle, Dennis A.; Sticca, Robert P.; Miller, Robert Clell; Leenstra, James L.; Peller, Patrick J.; Ginos, Brenda; Heying, Erica; Wu, Tsung-Teh; Drevyanko, Timothy F.; Ko, Stephen; Mattar, Bassam Ibrahim; Nikcevich, Daniel A.; Behrens, Robert J.; Khalil, Maged F.; Kim, George P.; Alberts, Steven R.
• Is Part Of: European journal of cancer. Volume 150(2021)
• Page Start: 214
• Page End: 223
• Publication Date: 2021-06
• Subjects: Esophageal adenocarcinoma -- Gastro-oesophageal adenocarcinoma -- Trimodality therapy -- nduction chemotherapy -- Radiation -- Surgery -- esophagectomy; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2021.03.025
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Aim: report primary results from the first multicentre randomised trial evaluating induction chemotherapy prior to trimodality therapy in patients with oesophageal or gastro-oesophageal junction adenocarcinoma. Notably, recent data from a single-institution randomised trial reported that induction chemotherapy prolonged overall survival (OS) in patients with well/moderately differentiated tumours. Methods: In this phase 2 trial (28 centres in the U.S. NCI-sponsored North Central Cancer Treatment Group [Alliance]), trimodality-eligible patients (T3-4 N0, Tany N+ ) were randomised to receive induction (docetaxel, oxaliplatin, capecitabine; Arm A) or no induction chemotherapy (Arm B) followed by oxaliplatin/5-fluorouracil/radiation and subsequent surgery. The primary endpoint was the rate of pathologic complete response (pathCR). Secondary/exploratory endpoints were OS and disease-free survival (DFS). Results: Of 55 patients evaluable for the primary endpoint, the pathCR rate was 28.6% (8/28) in A versus 40.7% (11/27) in B ( P = .34). Given interim results indicating futility, accrual was terminated, but patients were followed. After a median follow-up of 60.4 months, a longer median OS in Arm A versus B was unexpectedly observed (3-year rates 57.1% versus 41.7%, respectively) driven by longer DFS after margin-free surgery. In posthoc analysis, induction (versus no induction) chemotherapy was associated with significantly longer OS and DFS among patients with well/moderately differentiated tumours, but not among patients with poorly/undifferentiated tumours ( P interaction = 0.037). Conclusions: Adding induction chemotherapy prior to trimodality therapy did not improve the primary endpoint, pathCR. However, induction chemotherapy was associated with longer median OS, particularly among patients with well/moderately differentiated tumours. These findings may inform further development of curative-intent trials in this disease. Highlights: Adding chemotherapy before trimodality therapy did not improve tumour response. But it was unexpectedly associated with a longer median overall survival. This was observed especially in patients with well/moderately differentiated tumours. These findings are similar to those from a prior independent randomised trial. These new data can inform the development of curative-intent therapy in this disease.