Harry H Yoon1, Fang-Shu Ou2, Gamini S Soori3, Qian Shi4, Dennis A Wigle5, Robert P Sticca6, Robert Clell Miller7, James L Leenstra8, Patrick J Peller9, Brenda Ginos10, Erica Heying11, Tsung-Teh Wu12, Timothy F Drevyanko13, Stephen Ko14, Bassam Ibrahim Mattar15, Daniel A Nikcevich16, Robert J Behrens17, Maged F Khalil18, George P Kim19, Steven R Alberts20. 1. Mayo Clinic, Rochester, MN, USA. Electronic address: Yoon.Harry@mayo.edu. 2. Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA. Electronic address: Ou.Fang-Shu@mayo.edu. 3. Missouri Valley Cancer Consortium, Omaha, NE, USA. Electronic address: gsoori@nebraskacancer.com. 4. Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA. Electronic address: Shi.Qian2@mayo.edu. 5. Mayo Clinic, Rochester, MN, USA. Electronic address: Wigle.Dennis@mayo.edu. 6. Sanford Clinic North-Fargo, Fargo, ND, USA. Electronic address: robert.sticca@med.und.edu. 7. Mayo Clinic, Rochester, MN, USA. Electronic address: miller.robert@mayo.edu. 8. Mayo Clinic, Rochester, MN, USA. Electronic address: Leenstra.James@mayo.edu. 9. Mayo Clinic, Rochester, MN, USA. Electronic address: peller.patrick@mayo.edu. 10. Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA. Electronic address: Ginos.Brenda@mayo.edu. 11. Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA. Electronic address: Heying.Erica@mayo.edu. 12. Mayo Clinic, Rochester, MN, USA. Electronic address: Wu.TsungTeh@mayo.edu. 13. UnityPoint Health, Des Moines, IA, USA. Electronic address: timothy.drevyanko@unitypoint.org. 14. Mayo Clinic, Jacksonville, FL, USA. Electronic address: Ko.Stephen@mayo.edu. 15. Cancer Center of Kansas - Wichita, Wichita, KS, USA. Electronic address: bmattar@msn.com. 16. Duluth Community Clinical Oncology Program (COOP), Duluth, MN, USA. Electronic address: daniel.nikcevich@essentiahealth.org. 17. Iowa Wide Oncology Research Coalition, Des Moines, IA, USA. Electronic address: rbehrens@cancercenterofiowa.com. 18. Lehigh Valley Health Network, Allentown, Michigan Cancer Research Consortium, PA, USA. Electronic address: Maged.Khalil@lvhn.org. 19. 21(st) Century Oncology of Jacksonville, Jacksonville, FL, USA. Electronic address: george.kim@21co.com. 20. Mayo Clinic, Rochester, MN, USA. Electronic address: alberts.steven@mayo.edu.
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.
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.
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