Prognostic Impact of Early Treatment and Oxaliplatin Discontinuation in Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 11 Adjuvant Trials

Author(s): Claire Gallois, MD¹; Qian Shi, PhD²; Jeffrey P. Meyers, MD²; Timothy Iveson, MD³; Steven R. Alberts, MD, MPH⁴; Aimery de Gramont, MD⁵; Alberto F. Sobrero, PhD⁶; Daniel G. Haller, MD⁷; Eiji Oki, MD⁸; Anthony Frank Shields, MD, PhD⁹; Richard M. Goldberg, MD¹⁰; Rachel Kerr, MD¹¹; Sara Lonardi, MD¹²; Greg Yothers, PhD¹³; Caroline Kelly, PhD¹⁴; Ioannis Boukovinas, MD, PhD¹⁵; Roberto Labianca, MD¹⁶; Frank A. Sinicrope, MD⁴; Ioannis Souglakos, MD, PhD¹⁷; Takayuki Yoshino, MD¹⁸; Jeffrey A. Meyerhardt, MD, MPH¹⁹; Thierry André, MD, PhD²⁰; Demetris Papamichael, MD²¹; and Julien Taieb, MD, PhD¹

Source: DOI: 10.1200/JCO.21.02726 Journal of Clinical Oncology 41, no. 4 (February 01, 2023) 803-815.

Dr. Maen Hussein's Thoughts

Stopping oxaliplatinum and cont. of 5FU is better than stopping all chemotherapy. An option for patients with worsening neuropathy or other oxaliplatinum toxicity.

PURPOSE

Oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (CC) for 6 months remains a standard in high-risk stage III patients. Data are lacking as to whether early discontinuation of all treatment (ETD) or early discontinuation of oxaliplatin (EOD) could worsen the prognosis.

MATERIALS AND METHODS

We studied the prognostic impact of ETD and EOD in patients with stage III CC from the ACCENT/IDEA databases, where patients were planned to receive 6 months of infusional fluorouracil, leucovorin, and oxaliplatin or capecitabine plus oxaliplatin. ETD was defined as discontinuation of treatment and EOD as discontinuation of oxaliplatin only before patients had received a maximum of 75% of planned cycles. Association between ETD/EOD and overall survival and disease-free survival (DFS) were assessed by Cox models adjusted for established prognostic factors.

RESULTS

Analysis of ETD and EOD included 10,447 (20.9% with ETD) and 7,243 (18.8% with EOD) patients, respectively. Compared with patients without ETD or EOD, patients with ETD or EOD were statistically more likely to be women, with Eastern Cooperative Oncology Group performance status ≥ 1, and for ETD, older with a lower body mass index. In multivariable analyses, ETD was associated with a decrease in disease-free survival and overall survival (hazard ratio [HR], 1.61, P < .001 and HR, 1.73, P < .001), which was not the case for EOD (HR, 1.07, P = .3 and HR, 1.13, P = .1). However, patients who received < 50% of the planned cycles of oxaliplatin had poorer outcomes.

CONCLUSION

In patients treated with 6 months of oxaliplatin-based chemotherapy for stage III CC, ETD was associated with poorer oncologic outcomes. However, this was not the case for EOD. These data favor discontinuing oxaliplatin while continuing fluoropyrimidine in individuals with significant neurotoxicity having received > 50% of the planned 6-month chemotherapy.

Author Affiliations

¹Paris‐Cité University, Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC CARPEM, Paris, France; ²Department of Health Science Research, Mayo Clinic, Rochester, MN; ³Department of Medical Oncology, University of Southampton, Southampton, United Kingdom; ⁴Department of Oncology, Mayo Clinic, Rochester, MN; ⁵Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France; ⁶Medical Oncology, IRCCS San Martino IST, Genoa, Italy; ⁷Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, PA; ⁸Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; ⁹Karmanos Cancer Institute, Wayne State University, Detroit, MI; ¹⁰West Virginia University Cancer Institute and the Mary Babb Randolph Cancer Center, Morgantown, WV; ¹¹Department of Oncology, Oxford University, Oxford, United Kingdom; ¹²Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology IRCCS, Padua, Italy; ¹³Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA; ¹⁴Cancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; ¹⁵Bioclinic Thessaloniki Medical Oncology Unit, Thessaloniki, Greece; ¹⁶Ospdale Papa Giovanni XXIII, Bergamo, Italy; ¹⁷Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece; ¹⁸Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan; ¹⁹Dana-Farber Cancer Institute, Boston, MA; ²⁰Sorbonne Université, Department of Medical Oncology, Hôpital Saint-Antoine, Paris, France; ²¹Division of Medical Oncology, Bank Of Cyprus Oncology Centre, Nicosia, Cyprus

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