The phase 2 PARERE trial demonstrated that panitumumab, an anti-EGFR antibody guided by circulating tumor DNA (ctDNA), outperformed regorafenib in terms of response and survival rates among patients with chemorefractory metastatic colorectal cancer (mCRC) with RAS and BRAF wild-type (wt) status.

These results will first be presented by Chiara Cremolini, MD, University of Pisa, Pisa, Italy, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting at Chicago, Illinois.

This open-label, multicenter, randomized trial enrolled patients with RAS/BRAF wt mCRC who previously benefited from first-line anti-EGFR therapy and had received at least 1 intervening anti-EGFR-free regimen. Eligible patients were selected prospectively using ctDNA to confirm absence of resistance mutations (RAS/BRAF wt) at the time of retreatment.

The primary end point was overall survival (OS) and secondary end points included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and safety.

Between December 2020 and December 2024, 428 patients were molecularly screened, and 213 patients were randomized to receive either panitumumab followed by regorafenib (Arm A, n = 106) or regorafenib followed by panitumumab (Arm B, n = 107). Patients in Arm B were slightly older (median 64 years vs 62 years) and were less likely to have left-sided tumors (92% vs 88%). Both arms reported a median of 2 prior lines of therapy.

At a median follow-up of 23.5 months, 194 and 135 first and second progression events were recorded, respectively. Interim efficacy data showed superiority for first-line panitumumab (Arm A) in terms of ORR and PFS compared to first-line regorafenib (Arm B). Patients in Arm A demonstrated higher median PFS (4.1 months vs 2.4 months; harzard ratio [HR], 1.23; 95% confidence interval [Ci], 0.93 to 1.64 P = .15) and ORR (16% vs 1.9%; odds ratio [OR], 0.1; 95% CI, 0.18 to 0.56; P <.01) than patients in Arm B. Additionally, the DCR was also higher in Arm A than in Arm B (59.4% vs 31.8%; OR, 0.32; 95% CI, 0.18 to 0.56; P <.01).

Safety profiles were consistent with known adverse event patterns for both panitumumab and regorafenib.

"PARERE is the largest randomized trial demonstrating an ORR and PFS advantage in favor of liquid biopsy-guided anti-EGFR re-tx, compared to regorafenib, in the late-line setting of RAS/BRAF wt mCRC,” the researchers concluded.

Source:

Cremolini C, Ciracì P, Pietrantonio F, et al. Panitumumab retreatment followed by regorafenib versus the reverse sequence in chemorefractory metastatic colorectal cancer patients with RAS and BRAF wild-type circulating tumor DNA (ctDNA): Results of the phase II randomized PARERE trial by GONO. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract LBA3515.