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.

Abstract

4004 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 . [Table: see text]

Adjuvant Chemotherapy for Stage III Colon Cancer

“…The 5-year OS was not significantly different between 3 months (82.4%) and 6 months of treatment (82.8%) in the whole population (HR:1.02, 95%CI 0.95-1.11). Interestingly, for high-risk stage III patients treated with CAPOX, the absolute difference in 5-year OS rate between 3 and 6 months was only 1% (71.4% versus 72.4%, respectively) with an HR of 1.02 (95%CI 0.89-1.20), while for those treated with FOLFOX, the absolute difference in 5-year OS rate was 2.8% between the two treatment durations (72.5% versus 75.3%) with a HR of 1.12 (95%CI 0.98-1.27) [33].…”

Impact of relative dose intensity of oxaliplatin in adjuvant therapy among stage III colon cancer patients on early recurrence: a retrospective cohort study

“…Interestingly, the risk of early recurrence in patients with RDI-O < 60% concerned especially low-risk group. These results should be referred to the abovementioned IDEA project and CAPOX e cacy in low-risk group [20][21][22]. It seems, that RDI-O may be a more accurate re ection of the true patient-relevant bene t of adjuvant chemotherapy among stage III CC.…”

“…Tsai et al have shown that at least eight FOLFOX cycles are needed to have OS bene t, and seven to ensure DFS [19]. Moreover, in the International Duration Evaluation of Adjuvant Therapy (IDEA) project in stage III CC patients, the noninferiority of FOLFOX/CAPOX regimens used for 3 vs. 6 months was not demonstrated [20][21][22]. Although in the lower risk group (pT1-3/N1), the 3-month (4 cycles) CAPOX was as effective as the 6-month (8 cycles) treatment and the 3-year rate of DFS was 74.6% and 75.5%, respectively [20][21][22].…”

Impact of relative dose intensity of oxaliplatin in adjuvant therapy among stage III colon cancer patients on early recurrence: a retrospective cohort study

“…Tsai et al have shown that at least eight FOLFOX cycles are needed to have OS bene t, and seven to ensure DFS [19]. Moreover, in the International Duration Evaluation of Adjuvant Therapy (IDEA) project in stage III CC patients, the noninferiority of FOLFOX/CAPOX regimens used for 3 vs. 6 months was not demonstrated [20][21][22]. However, in the lower risk group (pT1-3/N1), the 3-month (4 cycles) CAPOX was as effective as the 6-month (8 cycles) treatment and the 3-year rate of DFS was 74.6% and 75.5%, respectively [20][21][22].…”