Panitumumab plus trifluridine-tipiracil confers survival advantage in RAS wild-type MCRC

In the third-line treatment of patients with refractory RAS wild-type metastatic colorectal cancer (MCRC), use of panitumumab plus the standard-of-care trifluridine-tipiracil appears to prolong progression-free survival (PFS) when compared with trifluridine-tipiracil alone, according to data from a phase II study.

The study included 62 patients with RAS wild-type MCRC who had 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. These patients were randomized to receive trifluridine-tipiracil alone (n=17; median age 66 years, 54.8 percent men) or in combination with panitumumab (n=31, combination group; median age 65 years, 61.3 percent men).

The primary endpoint of PFS was significantly longer in the panitumumab group than in the standard-of-care group (4.0 vs 2.5 months; hazard ratio [HR], 0.48, 95 percent confidence interval [CI], 0.28–0.82; p=0.007).

Pretreatment plasma RAS/BRAF wild-type circulating tumour (ct) DNA was able to pinpoint which patients achieved prolonged clinical benefit with panitumumab plus trifluridine-tipiracil vs trifluridine-tipiracil alone.

The PFS rates were 38.5 percent vs 13.0 percent at 6 months and 15.4 percent vs 0 percent at 12 months.

Results of a ctDNA liquid-biopsy extended mutation analysis in a subgroup of patients with baseline plasma RAS/BRAF WT ctDNA showed that in 15 of 23 patients (65.2 percent) whose tumours were wild type for KRAS, NRAS, BRAFV600E, EGFR, ERBB2, MAP2K1, and PIK3CA, the median PFS was 6.4 months. Among these 15 patients, two (13.3 percent) had partial response, 11 (73.3 percent) had stable disease, and two (13.3 percent) had disease progression as best response.