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 - 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
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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
SN - 0959-8049
VL - 150
SP - 214
EP - 223
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -