A new study demonstrated that, in treatment-naïve patients with metastatic colorectal cancer (mCRC), intermittent treatment with FOLFIRI and panitumumab was associated with long progression-free survival (PFS) and with less skin toxicity than a continuous treatment approach.
The study results were presented at the 2022 ASCO Annual Meeting by Antonio Avallone, MD, of Istituto Nazionale Tumori Fondazione G. Pascale in Naples, Italy, and colleagues.
In this prospective, open-label phase 2 trial (ClinicalTrials.gov Identifier: NCT04425239), patients with unresectable, treatment-naïve RAS/BRAF wild-type mCRC were randomly assigned to either of 2 study arms, and stratified based on numerous characteristics.
Arm A received continuous treatment with FOLFIRI (leucovorin calcium, 5-fluorouracil, and irinotecan) and panitumumab until disease progression, at which point patients may receive second-line therapy.
Arm B was the intermittent-treatment arm, and patients in this arm received 8 cycles of FOLFIRI and panitumumab with a treatment-free interval afterward. Treatment would resume for 8 cycles if progressive disease occurred off treatment, and this approach persisted unless the patient had progressive disease while on treatment.
Both arms received tumor assessments at 8-week intervals. The primary endpoint of the study was 1-year PFS on treatment (PFSOT).
A total of 137 patients were randomly assigned to arm A (69 patients) or arm B (68 patients). Median ages were 62 years in arm A and 66 years in arm B. The ECOG performance status score was 0 in 84% of patients in arm A and 72% in arm B. The right colon was involved in 17% of patients in arm A and 15% in arm B. Prior adjuvant therapy had been received by 22% in arm A and 31% in arm B. There was a single metastatic site in 33% of patients in arm A and in 26% in arm B.
The median follow-up was 20 months (IQR, 13 to 29), and the median number of treatment cycles per patient was 13 for each arm.
Arm A had a median PFSOT of 13.2 months (95% CI, 9.6-16.8), and the median PFSOT in arm B was 17.1 months (95% CI, 9.3-24.9). The 12-month PFSOT rates were 52.1% for arm A and 60.8% for arm B. The disease control rates were 94% for arm A and 90% for arm B.
The safety population included 69 patients from arm A and 67 patients from arm B. Grade 3 to 4 toxicities related to the skin were reported in 25% of patients in arm A and in 13% in arm B. Grade 3 or 4 neutropenia was reported in 23% in arm A and in 24% in arm B, and grade 3 or 4 diarrhea was reported in 13% and 15%, respectively. The intermittent approach also was reportedly associated with less toxicity-related treatment discontinuation.
The study investigators concluded that the trial met its primary endpoint and with intermittent treatment being associated with less skin toxicity than seen with continuous treatment. They also considered these results with intermittent treatment to be particularly relevant during the COVID-19 pandemic era.
Disclosures: Some authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Avallone A, Giuliani F, Nasti G, et al. Randomized intermittent or continuous panitumumab plus FOLFIRI (FOLFIRI/PANI) for first-line treatment of patients (pts) with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC): The IMPROVE study. Presented at ASCO 2022; June 3-7, 2022. Abstract 3503.