Overall survival (OS) and long-term disease-free survival (DFS) of three versus six months of adjuvant (adj) oxaliplatin and fluoropyrimidine-based therapy for patients (pts) with stage III colon cancer (CC): Final results from the IDEA (International Duration Evaluation of Adj chemotherapy) collaboration.

Authors

null

Alberto F. Sobrero

Ospedale Policlinico San Martino IRCCS, Genoa, Italy

Alberto F. Sobrero , Thierry Andre , Jeffrey A Meyerhardt , Axel Grothey , Timothy Iveson , Takayuki Yoshino , Ioannis Sougklakos , Jeffrey P. Meyers , Roberto Labianca , Mark P. Saunders , Dewi Vernerey , Takeharu Yamanaka , Ioannis Boukovinas , Eiji Oki , Vassilis Georgoulias , Valter Torri , Andrea Harkin , Julien Taieb , Anthony Frank Shields , Qian Shi

Organizations

Ospedale Policlinico San Martino IRCCS, Genoa, Italy, Saint-Antoine Hospital and Sorbonne Universités, Paris, France, Dana-Farber Cancer Institute, Boston, MA, West Cancer Center, Germantown, TN, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, National Cancer Center Hospital East, Kashiwa, Japan, University of Heraklion, Heraklion, Greece, Mayo Clinic, Rochester, MN, Cancer Center, ASST Papa Giovanni XXIII, Bergamo, Italy, Christie Hospital, Manchester, United Kingdom, Methodology and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon, France, Yokohama City University School of Medicine, Yokohama, Japan, Bioclinic Thessaloniki Medical Oncology Unit, Athens, Greece, Kyushu University, Fukuoka, Japan, Iaso General Hospital, Athens, Greece, Istituto Mario Negri, Milan, Italy, Cancer Research UK Clinical Trials Unit, Institute of Cancer Research, University of Glasgow, Glasgow, United Kingdom, Hôpital Européen Georges-Pompidou, Sorbonne Paris Cite/Paris Descartes University, Paris, France, Karmanos Cancer Institute, Wayne State University, Detroit, MI, Department of Health Science Research, Mayo Clinic, Rochester, MN

Research Funding

U.S. National Institutes of Health
U.S. National Institutes of Health, Other Government Agency

Background: In overall population, IDEA pooled analysis did not demonstrate non-inferiority (NI) regarding 3y DFS in pts with stage III CC receiving 3m vs. 6m of adj FOLFOX/CAPOX. However, in pts treated with CAPOX (especially in low-risk pts), 3m of therapy was as effective as 6m. Results of OS and 5y DFS are reported. Methods: OS was defined as time from enrollment to death due to all causes. OS NI margin was conservatively set to be Hazard Ratio (HR) = 1.11, which is equivalent to: the maximum acceptable loss of OS efficacy, by shortening treatment to 3m, was half of the OS efficacy gained in MOSAIC trial (i.e., 2.26% absolute reduction in 5y OS rate). Pre-planned sub-group analyses included by regimen and risk group for both OS and 5y DFS. NI was to be declared if the one-sided false discovery rate adjusted (FDRa) NI p-value < 0.025. Results: With an overall median survival follow-up of 72 m (range per study, 62 to 84 m), 2584 deaths and 3777 DFS events among 12,835 pts from six trials were observed. Across 6 studies, 39.5% of pts received CAPOX (rate by study, 0% to 75.1%). Overall, the 5y OS rate was 82.4% (3m) and 82.8% (6m), with estimated OS HR of 1.02 (95% confidence interval [CI], 0.95-1.11; FDRa NI p, 0.058) and absolute 5-y OS rate difference of -0.4% (95% CI, -2.1 to 1.3%). Overall, the 5y DFS rate was 69.1% (3m) and 70.8% (6m), with estimated DFS HR of 1.08 (95%CI, 1.01-1.15, FDRa NI p, 0.22). HRs (95% CI) within subgroups see table. Conclusions: 5y OS rate reported in IDEA trials was higher than historical rates, regardless of duration of therapy. While overall survival in IDEA did not meet prior statistical assumptions for NI in overall population, the 0.4% difference in 5y OS should be placed in clinical context. OS and 5y DFS results continue to support the use of 3m adjuvant CAPOX for the vast majority of stage III colon cancer pts. This conclusion is strengthened by the substantial reduction of toxicities, inconveniencies and cost associated with shorter treatment duration. Clinical trial information: NCT01150045; 2009-010384-16; NCT00749450; ISRCTN59757862; 2007-003957-10; UMIN000008543; 2007-000354.

OSLong-term DFS
CAPOX0.96 (0.85, 1.08)0.98 (0.88, 1.08)
FOLFOX1.07 (0.97, 1.18)1.16 (1.06, 1.26)
Low Risk (T1-3 N1)0.95 (0.84, 1.08)1.04 (0.94, 1.14)
High Risk (T4 or N2)1.08 (0.98, 1.19)1.12 (1.03, 1.22)

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Oral Abstract Session

Session Title

Gastrointestinal Cancer—Colorectal and Anal

Track

Gastrointestinal Cancer—Colorectal and Anal

Sub Track

Colorectal Cancer–Local-Regional Disease

Clinical Trial Registration Number

NCT01150045; 2009-010384-16; NCT00749450; ISRCTN59757862; 2007-003957-10; UMIN000008543; 2007-000354

Citation

J Clin Oncol 38: 2020 (suppl; abstr 4004)

DOI

10.1200/JCO.2020.38.15_suppl.4004

Abstract #

4004

Abstract Disclosures