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Clinical Trial
. 2024 Aug 1;159(8):865-871.
doi: 10.1001/jamasurg.2024.1555.

Time From Colorectal Cancer Surgery to Adjuvant Chemotherapy: Post Hoc Analysis of the SCOT Randomized Clinical Trial

Mikail Gögenur  1 , Andreas Weinberger Rosen  1 , Timothy Iveson  2 , Rachel S Kerr  3 , Mark P Saunders  4 , Jim Cassidy  5 , Josep Tabernero  6 , Andrew Haydon  7 , Bengt Glimelius  8 , Andrea Harkin  5 , Karen Allan  5 , Sarah Pearson  9 , Kathleen A Boyd  10 , Andrew H Briggs  10   11 , Ashita Waterston  12 , Louise Medley  13 , Richard Ellis  14 , Amandeep S Dhadda  15 , Mark Harrison  16 , Stephen Falk  17 , Charlotte Rees  2 , Rene K Olesen  18 , David Propper  2   19 , John Bridgewater  20 , Ashraf Azzabi  21 , David Cunningham  22 , Tamas Hickish  23 , Simon Gollins  24 , Harpreet S Wasan  25 , Caroline Kelly  5 , Ismail Gögenur  1   26   27 , Niels Henrik Holländer  28
Affiliations
Clinical Trial

Time From Colorectal Cancer Surgery to Adjuvant Chemotherapy: Post Hoc Analysis of the SCOT Randomized Clinical Trial

Mikail Gögenur et al. JAMA Surg. .

Abstract

Importance: The timing of adjuvant chemotherapy after surgery for colorectal cancer and its association with long-term outcomes have been investigated in national cohort studies, with no consensus on the optimal time from surgery to adjuvant chemotherapy.

Objective: To analyze the association between the timing of adjuvant chemotherapy after surgery for colorectal cancer and disease-free survival.

Design, setting, and participants: This is a post hoc analysis of the phase 3 SCOT randomized clinical trial, from 244 centers in 6 countries, investigating the noninferiority of 3 vs 6 months of adjuvant chemotherapy. Patients with high-risk stage II or stage III nonmetastatic colorectal cancer who underwent curative-intended surgery were randomized to either 3 or 6 months of adjuvant chemotherapy consisting of fluoropyrimidine and oxaliplatin regimens. Those with complete information on the date of surgery, treatment type, and long-term follow-up were investigated for the primary and secondary end points. Data were analyzed from May 2022 to February 2024.

Intervention: In the post hoc analysis, patients were grouped according to the start of adjuvant chemotherapy being less than 6 weeks vs greater than 6 weeks after surgery.

Main outcomes and measures: The primary end point was disease-free survival. The secondary end points were adverse events in the total treatment period or the first cycle of adjuvant chemotherapy.

Results: A total of 5719 patients (2251 [39.4%] female; mean [SD] age, 63.4 [9.3] years) were included in the primary analysis after data curation; among them, 914 were in the early-start group and 4805 were in the late-start group. Median (IQR) follow-up was 72.0 (47.3-88.1) months, with a median (IQR) of 56 (41-66) days from surgery to chemotherapy. Five-year disease-free survival was 78.0% (95% CI, 75.3%-80.8%) in the early-start group and 73.2% (95% CI, 72.0%-74.5%) in the late-start group. In an adjusted Cox regression analysis, the start of adjuvant chemotherapy greater than 6 weeks after surgery was associated with worse disease-free survival (hazard ratio, 1.24; 95% CI, 1.06-1.46; P = .01). In adjusted logistic regression models, there was no association with adverse events in the total treatment period (odds ratio, 0.82; 95% CI, 0.65-1.04; P = .09) or adverse events in the first cycle of treatment (odds ratio, 0.77; 95% CI, 0.56-1.09; P = .13).

Conclusions and relevance: In this international population of patients with high-risk stage II and stage III colorectal cancer, starting adjuvant chemotherapy more than 6 weeks after surgery was associated with worse disease-free survival, with no difference in adverse events between the groups.

Trial registration: isrctn.org Identifier: ISRCTN59757862.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Saunders reported receiving personal fees from Servier, Bayer, Takeda, and MSD outside the submitted work. Dr Tabernero reported receiving personal fees from Alentis Therapeutics, AstraZeneca, Boehringer Ingelheim, Cardiff Oncology, CARSgen Therapeutics, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, hC Bioscience, Ikena Oncology, Immodulon Therapeutics, Inspirna Inc, Lilly, Medscape Education, Menarini, Merck Serono, Merus, Mirati, MSD, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, PeerView Institute for Medical Education, Peptomyc, Pfizer, Physicians Education Resource, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Takeda Oncology, and Tolremo and holding stock in Oniria Therapeutics, Alentis Therapeutics, Pangaea Oncology, and 1TRIALSP outside the submitted work. Dr Glimelius reported receiving grants from the Swedish Cancer Society during the conduct of the study. Dr Pearson reported receiving grants from the National Institute for Health and Care Research during the conduct of the study; and receiving personal fees from Cancer Research UK outside the submitted work. Dr Boyd reported receiving grants from the National Institute for Health Research during the conduct of the study; and receiving grants from Cancer Research UK outside the submitted work. Dr Briggs reported receiving personal fees from Daiichi Sankyo, AstraZeneca, Boehringer Ingelheim, Idorsia, Rhythm, Gilead, GSK, Roche, Novartis, Eisai, and Takeda outside the submitted work. Dr Ellis reported receiving personal fees from Eisai and Amgen outside the submitted work. Dr Hickish reported receiving grants from the National Institute for Health and Care Research during the conduct of the study; and receiving grants from Pfizer, Pierre Fabre, AstraZeneca, Novartis, and the National Institute for Health and Care Research, having a patent issued for a neuropathy device, and holding stock in iQ HealthTech outside the submitted work. Dr I. Gögenur reported receiving personal fees from Boehringer Ingelheim, Pharmacosmos, Ethicon, and MSD and grants from Pharmacosmos outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Unadjusted Disease-Free Survival by Study Group
Figure 2.
Figure 2.. Subgroup Analysis of the Association of Time to Adjuvant Chemotherapy Start and Disease-Free Survival
Arm 1 includes patients randomized to 3 months of therapy; arm 2, patients randomized to 6 months of therapy. CAPOX indicates capecitabine and oxaliplatin; FOLFOX, fluorouracil, leucovorin, and oxaliplatin; HR, hazard ratio; IR, incidence rate; WHO PS, World Health Organization performance status. aThe IR is per 10 000 person-years.
See this image and copyright information in PMC

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