SAPPHIRE: a randomised phase II study of planned discontinuation or continuous treatment of oxaliplatin after six cycles of modified FOLFOX6 plus panitumumab in patients with colorectal cancer

Abstract Background Fluorouracil (5-FU), leucovorin (LV) and oxaliplatin( FOLFOX) plus panitumumabtherapy is a commonly used first-line chemotherapy for metastatic colorectal cancer (mCRC). However, the long-term administration of oxaliplatinis associated with peripheral neuropathy (PN). We investigated whether the planned discontinuation of oxaliplatinafter FOLFOXplus panitumumabtherapy can maintain efficacy and reduce PN incidence. Patients and methods Chemotherapy-naive patients with RAS wild-type mCRC, aged ≥20 years, were enrolled and received six cycles of modified FOLFOX6 (mFOLFOX6) plus panitumumabas induction therapy. Patients who completed induction therapy without progression were randomised to mFOLFOX6 plus panitumumab(group A) or to 5-FU/LV plus panitumumab(group B). The primary end-point was the progression-free survival (PFS) rate at 9 months after randomisation. The secondary end-points were PFS, overall survival (OS), time to treatment failure (TTF), response rate (RR) and safety. Results In total, 164 patients were enrolled; of whom, 113 patients were then randomised (group A, n = 56; group B, n = 57). The median follow-up after randomisation was 19.6 months. The PFS rates at 9 months and median PFS were 46.4% (80% confidence interval [CI], 38.1–54.9) and 9.1 months (95% CI, 8.6–11.1) in group A, compared with 47.4% (80% CI, 39.1–55.8) and 9.3 months (95% CI, 6.0–13.0) in group B, respectively. RR, OS and TTF were also similar in both groups. Grade ≥2 PN incidence was lower in group B (9.3%) than in group A (35.7%). Conclusion Planned discontinuation of oxaliplatinafter six cycles of mFOLFOX6 plus panitumumabis a potential treatment option in patients with mCRC, achieving similar efficacy while reducing oxaliplatin-associated PN compared with mFOLFOX6 plus panitumumab. Trial registration number NCT02337946