An Italian phase II trial (IMPROVE) has revealed that intermittent administration of panitumumab in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) demonstrates promising efficacy and reduced toxicity in the first-line treatment of patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC). The study, published in the Journal of Clinical Oncology, suggests a potential shift in how this regimen is administered to improve patient outcomes.
Study Design and Key Findings
The noncomparative multicenter trial, conducted between May 2018 and June 2021, randomly assigned 137 patients to either continuous FOLFIRI plus panitumumab until disease progression (n = 69) or an intermittent approach (n = 68). The intermittent group received eight cycles of induction treatment with FOLFIRI plus panitumumab, followed by a treatment-free interval until disease progression, at which point another treatment period of up to eight cycles was restarted. Both groups received panitumumab every two weeks at 6 mg/kg, along with irinotecan at 180 mg/m2, leucovorin at 200 mg/m2, and fluorouracil as a 400 mg/m2 bolus followed by 2,400 mg/m2 as a 48-hour continuous infusion. The primary endpoint was progression-free survival on treatment at 12 months, with a null hypothesis for median progression-free survival-on treatment of less than 7 months.
After a median follow-up of 43.2 months, the intermittent group demonstrated a median progression-free survival on treatment of 17.5 months, compared to 11.2 months in the continuous group. The rates of 12-month progression-free survival on treatment were 58.5% and 45.7% in the intermittent and continuous groups, respectively. Overall response rates were 61.2% and 68.1%, while median overall survival was 35.1 months and 36.3 months in the intermittent and continuous groups, respectively.
Treatment-Free Interval and Adverse Events
Notably, the median treatment-free interval in the intermittent group between the end of treatment induction and the first round of treatment reinduction was 4 months (range = 2–46 months). This suggests that patients in the intermittent arm experienced a significant period without active treatment, potentially improving their quality of life.
Furthermore, the overall rates of grade >2 skin panitumumab-related adverse events were lower in the intermittent group (17.9%) compared to the continuous group (30.3%), indicating a reduction in toxicity with the intermittent approach.
Implications for Clinical Practice
The investigators concluded that intermittent FOLFIRI plus panitumumab after the induction phase is feasible and met the primary endpoint with reduced toxicity, while allowing patients more time off treatment. These findings suggest that an intermittent approach could be a viable option for first-line treatment of RAS/BRAF wild-type mCRC, potentially improving patient outcomes and quality of life.
According to Antonio Avallone, MD, of the Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Napoli, corresponding author of the Journal of Clinical Oncology article, this approach offers a balance between efficacy and tolerability, which is crucial in managing metastatic colorectal cancer.
