Multicenter phase 2 trial of intermittent versus continuous first-line panitumumab plus FOLFIRI for RAS/BRAF wild-type metastatic colorectal cancer

Panitumumab (PAN) plus chemotherapy is a standard first-line treatment for RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC). However, clinical application of this treatment is limited by the inevitable development of resistance and anti-EGFR-induced skin toxicity. The multicenter phase 2 IMPROVE trial in Italy evaluated intermittent use of first-line PAN plus FOLFIRI for RAS/BRAF wt mCRC. Patients were randomized to continuous PAN-FOLFIRI until progression (arm A) or eight cycles of PAN-FOLFIRI, followed by treatment-free interval until progression, followed by another eight cycles of PAN-FOLFIRI followed by treatment-free interval until progression (arm B). The primary endpoint was progression-free survival on treatment (PFSot) rate at 12 months. Tne median number of cycles was 13 in arm A and 16 in arm B. The median PFSot was 11.2 months in arm A and 17.5 months in arm B, with 12-months PFSot rates of 45.7% and 58.8%, respectively. Median overall survival was 36.3 and 35.1 months in arms A and B, respectively. The overall rate of grade >2 PAN-related skin adverse events was 30.3% in arm A and 17.9% in arm B. The authors conclude that intermittent PAN plus FOLFIRI after the induction phase was feasible, with reduced toxicity while allowing patients more time off treatment.