Prospective pooled analysis of six phase III trials investigating duration of adjuvant (adjuv) oxaliplatin-based therapy (3 vs 6 months) for patients (pts) with stage III colon cancer (CC): The IDEA (International Duration Evaluation of Adjuvant chemotherapy) collaboration.

Abstract

LBA1 Background: Since 2004, 6 months (m) of oxaliplatin (oxali)-based treatment has been the standard of care as adjuvant therapy for stage III CC. Since oxali is associated with cumulative neurotoxicity, shorter duration of adjuv therapy could spare pts toxicity and lead to substantial saving in health expenditures. Methods: A prospective, pre-planned pooled analysis of 6 concurrently conducted randomized phase III trials (SCOT, TOSCA, Alliance/SWOG 80702, IDEA France (GERCOR/PRODIGE), ACHIEVE, HORG) was performed to evaluate the non-inferiority (NI) of 3m compared with 6m (ref) of adjuv FOLFOX/XELOX. The primary endpoint was disease-free survival (DFS), defined as time from enrolment to relapse, 2nd CRC, and death (all causes). NI was to be declared if the 2-sided 95% confidence interval (CI) for DFS hazard ratio (HR 3m v 6m) estimated by a stratified Cox model was below 1.12. NI was examined within regimen and stage subgroups as pre-planned. Results: The analysis included 12,834 pts from 12 countries, accrued from 6/07 to 12/15. Stage distribution: 13% T1-2, 66% T3, 21% T4; 28% N2; 40% received XELOX. G3+ neurotoxicity was higher in the 6m v 3m arm (16 v 3% FOLFOX, 9 v 3% XELOX, p<0.0001). With a median follow-up of 39 mos, 3263 DFS events were observed. Overall, the 3 year DFS rate was 74.6% (3m) and 75.5% (6m), with estimated DFS HR of 1.07 (95%CI, 1.00-1.15). The 3m v 6m DFS HRs were 1.16 (95%CI, 1.06-1.26) and 0.95 (95% CI, 0.85-1.06) for FOLFOX and XELOX treated pts, respectively. The 3m v 6m DFS HRs were 1.01 (95%CI, 0.90-1.12) in T1-3 N1, and 1.12 (95%CI, 1.03-1.23) for T4 or N2 pts. Conclusions: While NI was not established for the overall cohort, NI of 3m v 6m oxali-based adjuv therapy was supported for XELOX. As each IDEA trial treated varying proportions of pts with XELOX (0 to 75%), the regimen interaction likely produced the differential outcomes observed between individual studies. Certain substages (T1-3 N1) also showed NI for 3m v 6m. These data provide a framework for discussions on risks and benefits of individualized adjuv therapy approaches. Support: U10CA180821, U10CA180882, U10CA180888, U10CA180835, INCA, PHRC2009, EME 09/800/34, HTA 14/140/84, CRUK C1348/A15960, JFMC. Clinical trial information: NCT01150045.

Impact of number of cycles of platinum-based first-line chemotherapy for advanced urothelial carcinoma

“…There was no significant difference in OS between those receiving 3-5 versus 6-9 cycles of platinum-based first-line chemotherapy (HR 1.02, p=0.91). We also observed no significant interactions with the type of platinum and "completed planned chemotherapy" as defined by the and recent data also suggest that 3 months of adjuvant therapy may be adequate [27][28][29] . In the case of ovarian cancer, 6 cycles of platinum-based chemotherapy are targeted by convention, with no data refining the necessity of 6 cycles 30 .…”

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].…”

ASCO- und ESMO-Update 2017 – Neuigkeiten vom 53. Meeting der American Society of Clinical Oncology/ASCO 2017 und European Society for Medical Oncology/ESMO-Congress 2017

“…15 % der Patienten noch nach 4 Jahren an einer klinisch relevanten peripheren Neuropathie. Auf dem ASCO 2017 wurde die IDEA-Initiative als Abstrakt Nummer 1 in der Plenarsitzung vorgestellt, die in einer internationalen Kollaboration die Nicht-Unterlegenheit einer dreimonatigen adjuvanten Oxaliplatin-Kombination gegenüber einer sechsmonatigen Therapie prüfte [22]. Auf dem ESMO wurden diese Daten aktualisiert [23].…”