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

Eur J Cancer. 2021 Jun:150:214-223. doi: 10.1016/j.ejca.2021.03.025. Epub 2021 Apr 29.

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 (T3-4N0, 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).

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 (Pinteraction = 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.

Trial registration: ClinicalTrials.gov NCT00938470.

Keywords: Esophageal adenocarcinoma; Gastro-oesophageal adenocarcinoma; Radiation; Surgery; Trimodality therapy; esophagectomy; nduction chemotherapy.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Differentiation
  • Chemoradiotherapy, Adjuvant* / adverse effects
  • Chemoradiotherapy, Adjuvant* / mortality
  • Disease-Free Survival
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / therapy*
  • Esophagectomy* / adverse effects
  • Esophagectomy* / mortality
  • Female
  • Humans
  • Induction Chemotherapy* / adverse effects
  • Induction Chemotherapy* / mortality
  • Male
  • Middle Aged
  • Neoadjuvant Therapy* / adverse effects
  • Neoadjuvant Therapy* / mortality
  • Time Factors
  • United States

Supplementary concepts

  • Adenocarcinoma Of Esophagus

Associated data

  • ClinicalTrials.gov/NCT00938470