Pathological response guides adjuvant 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy in surgically resected gastro-oesophageal cancer (SPACE-FLOT): international cohort study
SPACE-FLOT Investigators, David S. Liu, Margaret M Lee, Katheryn Hall, David I. Watson, Lorenzo Ferri, Jimmy Bok Yan So, Claire L. Donohoe, Michael Michael, Niall C. Tebbutt, Darren Wong, Cuong P Duong, Tim Bright, Ahmad Aly, Sonia Gill, Chao Cheng, Su Kah Goh, Matthew Read, James Tan, Sean R. Stevens, Enoch Wong, Geraldine Ooi, Yick Ho Lam, Eunice Lee, David Williams, Louise Jackett, Chun Chan, Garett Smith, David Chan, Neil D. Merrett, Sivakumar Gananadha, Harsh Kanhere, Lauren R. Kennedy-Metz, B. Mark Smithers, Janine Thomas, Michael Bozin, Lynn Chong, Krinal Mori, Mary Ann Johnson, Sarah A. Martin, Val Usatoff, Rod Jacobs, Yahya Al-Habbal, Chon Hann Liew, Fredrick Huynh, Robert Bohmer, Girish Pande, Jurstine Daruwalla, Mo Ballal, Deanna Lee, Rukshan Ranjan, Andrew D. MacCormick, James M. Wilkins, Sharon Pattison, Nicholas Evennett, James M. Wilkins, Jason Robertson, M H Pang, Alexandra Gordon, Simon Bann, Yu Kai Lim, Inian Samarasam, Ramesh Gurunathan, Jonathan Yeung, Frances Allison, Aya Siblini, Ewen A. Griffiths, Alexander W. Phillips, Pooja Prasad, Sheraz Markar, Swathikan Chidambaram, David Chan, Thomas Murphy, John Reynolds, Magnus Nilsson, Fredrik Klevebro, Guillaume Piessen, Justine Lerooy, Bas P. L. Wijnhoven, Charlène van der Zijden, Richard van Hillegersberg, Lianne Triemstra, Jelle P. Ruurda, Mark I. van Berge Henegouwen, Suzanne S. Gisbertz, Pietro Maria Lombardi, Aleksandra Edmondson, Joe Wei, Aldenb Lorenzo, Sam Alhayo, Aaditya Narendra, Aadil Rahim, Rosemary Ho, Jeremy Granger, Steven Tran, Michalis Koullouros, Alain Nguyen, Christina McVeay, Siang Wei Gan, Eve Hopping
Abstract
BACKGROUND: Many patients with locally advanced gastro-oesophageal cancers are unable to complete adjuvant 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy, raising questions about its therapeutic utility. The aim of this study was to examine whether pathological response to neoadjuvant FLOT can guide its adjuvant use. METHODS: Patients with non-metastatic gastro-oesophageal adenocarcinoma who received neoadjuvant FLOT and underwent surgery from 1 January 2017 to 1 January 2022 from 43 hospitals across 12 countries were analysed. Pathological response was assessed using tumour regression grading systems, trichotomized into minimal responders (MR; worst category), complete responders (CR; pCR), and partial responders (PR; between MR and CR). Survival outcomes of patients who did and did not receive adjuvant FLOT were compared using Kaplan-Meier, Cox regression, propensity score matched, and sensitivity analysis. RESULTS: A total of 1887 patients (459 MR, 221 CR, and 1207 PR) were evaluated. The median follow-up was 25.5 (interquartile range 15.0-39.1) months. In the MR group, there was no difference in disease-free survival (DFS; HR 1.03 (95% c.i. 0.78 to 1.36), P = 0.836) between those who did and did not receive adjuvant FLOT. Whilst there was a difference in non-adjusted OS, this became statistically non-significant after adjusting for baseline characteristics (HR 0.96 (95% c.i. 0.70 to 1.30), P = 0.801). In the CR group, there was no difference in DFS (HR 0.88 (95% c.i. 0.41 to 1.85), P = 0.724) or OS (HR 0.69 (95% c.i. 0.31 to 1.54), P = 0.343) between those who did and did not receive adjuvant FLOT. In the PR group, adjuvant FLOT conferred a significant DFS (HR 0.68 (95% c.i. 0.55 to 0.86), P < 0.001) and OS (HR 0.55 (95% c.i. 0.44 to 0.69), P < 0.001) benefit. CONCLUSION: Pathological response to neoadjuvant FLOT may guide the use of adjuvant FLOT, enabling personalized approaches to treatment.