Platinum-sensitivity in metastatic colorectal cancer: towards a definition

First-line oxaliplatin-based therapy is the standard treatment of metastatic colorectal cancer (mCRC), but its dose-limiting toxicity is sensory neuropathy. The OPTIMisation of OXaliplatin (OPTIMOX) stop-and-go approach with oxaliplatin-free interval (OFI) offers a reasonable strategy. Influence of the first-line oxaliplatin-based treatment efficacy and the duration of OFI on tumour sensitivity to oxaliplatin reintroduction were investigated.

This was a pooled analysis of OPTIMOX1 and OPTIMOX2 studies, on 285 patients with previously untreated mCRC and FOLFOX reintroduction. An optimal OFI was estimated. Efficacy endpoints measured from reintroduction of FOLFOX included response rate (RR), progression-free survival (PFS) and overall survival (OS).

Two groups of OFI <6 and ≥ 6 months, were defined. The RR following FOLFOX reintroduction were 14% and 22% in patients with an OFI <6 and ≥ 6 months, respectively (overall RR 19%). The median PFS after FOLFOX reintroduction following OFI< 6 and ≥ 6 months were 3.0 [95% confidence intervals (CI): 2.7-3.7] and 5.5 months [95% CI: 4.8-6.5], respectively. The median OS following OFI <6 months was 8.8 months [95% CI: 7.5-10.5] and OFI ≥ 6 was months 16.8 months [95% CI: 15.3-19.6]. In the case of partial response (PR), median PFS and OS were 4.6 [95% CI: 4.1-5.0] and 14 months [95% CI: 12.1-16.4], respectively, whereas in patients with initial stable disease (SD) 3.4 [95% CI: 2.7-4.7] and 10.3 months [95% CI: 7.3-12.9], respectively.

A sensitive population of patients more likely to benefit from oxaliplatin reintroduction is defined by the efficacy of induction therapy followed by an OFI of at least 6 months between two periods of FOLFOX therapy. OFI of < 6 months identifies a subgroup of partially-resistant patients who can still benefit from oxaliplatin reintroduction.