Metastatic colorectal cancer (mCRC) remains a major clinical challenge, particularly for patients with RAS and BRAF wild-type (wt) tumours. Panitumumab, an anti-EGFR monoclonal antibody, combined with chemotherapy, is standard in this population but is often limited by resistance and toxicity. The phase II IMPROVE trial evaluated whether an intermittent strategy with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus panitumumab could reduce toxicity while maintaining efficacy in first-line treatment.1
IMPROVE was an Italian, open-label, multi-centre, randomised, non-comparative phase II trial. Patients with unresectable RAS/BRAF wt mCRC were randomised 1:1 to continuous FOLFIRI plus panitumumab until progression (arm A) or an intermittent schedule (arm B) consisting of an eight-cycle induction phase, followed by a treatment-free interval until progression. At this point, another treatment period of up to eight cycles is restarted. The intermittent strategy can be continued until progression on treatment is observed. The primary endpoint was progression-free survival on treatment (PFSot) at 12 months. Secondary outcomes included overall survival (OS), response rates, and safety.
A total of 137 patients were enrolled. At a median follow-up of 43.2 months, the intermittent treatment strategy met its primary endpoint, with a 12-month PFSot rate of 58.5% vs 45.7% in the continuous arm. Median PFSot was 17.5 months for intermittent therapy and 11.2 months for continuous therapy. Median OS was similar between arms, 35.1 months (intermittent) and 36.3 months (continuous). The overall response rates were 61.2% in the intermittent arm compared to 68.1% in the continuous arm. Notably, intermittent treatment reduced grade >2 skin toxicity related to panitumumab (17.9% vs 30.3%) and allowed more time off treatment. The benefits of intermittent therapy were most pronounced in patients with left-sided tumours.
Intermittent panitumumab plus FOLFIRI demonstrated reduced toxicity and comparable survival outcomes vs continuous therapy in patients with RAS/BRAF wt mCRC.
Top
