TY - JOUR
T1 - Induction versus no induction chemotherapy before neoadjuvant chemoradiotherapy and surgery in oesophageal adenocarcinoma
T2 - a multicentre randomised phase II trial (NCCTG N0849 [Alliance])
AU - Yoon, Harry H.
AU - Ou, Fang Shu
AU - Soori, Gamini S.
AU - Shi, Qian
AU - Wigle, Dennis A.
AU - Sticca, Robert P.
AU - Miller, Robert Clell
AU - Leenstra, James L.
AU - Peller, Patrick J.
AU - Ginos, Brenda
AU - Heying, Erica
AU - Wu, Tsung Teh
AU - Drevyanko, Timothy F.
AU - Ko, Stephen
AU - Mattar, Bassam Ibrahim
AU - Nikcevich, Daniel A.
AU - Behrens, Robert J.
AU - Khalil, Maged F.
AU - Kim, George P.
AU - Alberts, Steven R.
N1 - Funding Information:
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), U10CA180790 and U10CA180888 (SWOG). https://acknowledgments.alliancefound.org .The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - Esophageal adenocarcinoma
KW - Gastro-oesophageal adenocarcinoma
KW - Radiation
KW - Surgery
KW - Trimodality therapy
KW - esophagectomy
KW - nduction chemotherapy
UR - http://www.scopus.com/inward/record.url?scp=85105262876&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85105262876&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2021.03.025
DO - 10.1016/j.ejca.2021.03.025
M3 - Article
C2 - 33934058
AN - SCOPUS:85105262876
VL - 150
SP - 214
EP - 223
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
ER -