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

• DOI: 10.1016/j.ejca.2021.03.025
• Publication Date: 2021-04-30T01:55:57Z
• Authors: Harry H. Yoon; Fang-Shu Ou; Gamini S. Soori; Qian Shi; Dennis A. Wigle; Robert P. Sticca; Robert Clell Miller; James L. Leenstra; Patrick J. Peller; Brenda Ginos; Erica Heying; Tsung-Teh Wu; Timothy F. Drevyanko; Stephen Ko; Bassam Ibrahim Ma...; Daniel A. Nikcevich; Robert J. Behrens; Maged F. Khalil; George P. Kim; Steven R. Alberts
• Keywords: Adult; Aged, 80 and over; Male; Time Factors; Esophageal Neoplasms; Cell Differentiation; Chemoradiotherapy, Adjuvant; Induction Chemotherapy; Adenocarcinoma; Middle Aged; Disease-Free Survival; Neoadjuvant Therapy; United States; 3. Good health; Esophagectomy; 03 medical and health sciences; 0302 clinical medicine; Humans; Female; Aged

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.In this phase 2 trial (28 centres in the U.S. NCI-sponsored North Central Cancer Treatment Group [Alliance]), trimodality-eligible patients (T3-4N0, TanyN+) 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).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 (Pinteraction = 0.037).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.