In the Italian phase II VELO trial reported in JAMA Oncology, Napolitano et al found that anti-EGFR treatment rechallenge with the addition of panitumumab to trifluridine/tipiracil improved progression-free survival in the third-line setting for patients with RAS wild-type metastatic colorectal cancer.
Study Details
In the open-label multicenter trial, 62 patients with a partial or complete response to first-line chemotherapy plus an anti-EGFR monoclonal antibody and an anti-EGFR drug-free interval of at least 4 months during second-line therapy were randomly assigned between June 2019 and April 2022 to receive trifluridine/tipiracil with (n = 31) or without (n = 31) panitumumab. The primary endpoint was progression-free survival.
Progression-Free Survival
Median progression-free survival was 4.0 months (95% confidence interval [CI] = 2.8–5.3 months) in the panitumumab group vs 2.5 months (95% CI = 1.4–3.6 months) in the control group (hazard ratio [HR] = 0.48, 95% CI = 0.28–0.82, P = .007); rates at 6 and 12 months were 35.5% vs 9.7% (P = .02) and 12.9% vs 0% (P = .04).
Among patients with pretreatment plasma RAS/BRAF wild-type circulating tumor DNA (ctDNA), median progression-free survival was 4.5 months (95% CI = 2.2–6.8 months) in the panitumumab group vs 2.6 months (95% CI = 1.0–4.3 months) in the control group (HR = 0.48, 95% CI = 0.26–0.89, P = .02); rates at 6 and 12 months were 38.5% vs 13.0% (P = .047) and 15.4% vs 0% (P = .052).
KEY POINTS
- The addition of panitumumab to trifluridine/tipiracil significantly improved progression-free survival.
- Among patients with pretreatment plasma RAS/BRAF wild-type ctDNA, median progression-free survival was 4.5 vs 2.6 months, with 6-month rates of 38.5% vs 13.0%.
Among 23 patients in the panitumumab group with RAS/BRAF wild-type ctDNA, liquid biopsy extended mutation analysis showed that 15 were wild-type for KRAS, NRAS, BRAF V600E, EGFR, ERBB2, MAP2K1, and PIK3CA. Among these 15 patients, median progression-free survival was 6.4 months (95% CI = 3.7–9.2 months); best response among these patients was partial response in 2, stable disease in 11, and progressive disease in 2.
Adverse Events
The median number of treatment cycles was four (range = 1–26) in the panitumumab group and two (range = 1–10) in the control group. Grade 3 or 4 adverse events occurred in 16 patients (51.6%) in the panitumumab group vs 9 (29.0%) in the control group. Adverse events led to dose reductions in 51.6% vs 29.0% of patients (P = .07). No treatment discontinuations occurred due to adverse events, and no treatment-related deaths were observed.
The investigators concluded, “In this randomized clinical trial, third-line treatment with the anti-EGFR monoclonal antibody panitumumab plus the standard-of-care trifluridine/tipiracil resulted in improved progression-free survival compared with treatment with trifluridine/tipiracil alone among patients with refractory RAS wild-type metastatic colorectal cancer. The findings support the clinical utility of liquid biopsy–guided anti-EGFR rechallenge therapy for refractory RAS wild-type metastatic colorectal cancer.”
Teresa Troiani, MD, PhD, of the Department of Precision Medicine, Università Degli Studi Della Campania “Luigi Vanvitelli,” Napoli, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by a grant from the Regione Campania. For full disclosures of the study authors, visit jamanetwork.com.
