Panitumumab Plus Regorafenib Treatment Sequence Did Not Significantly Impact Survival in RAS/BRAF Wild-Type Metastatic Colorectal Cancer
Final results from the phase 2 PARERE study demonstrate that treatment sequence strategy of panitumumab plus regorafenib did not significantly impact overall survival (OS) results among patients with RAS and BRAF wild-type metastatic colorectal cancer (mCRC).
These findings were presented by Marco Maria Germani, MD, University of Pisa, Pisa, Italy, at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.
In this multicenter, open-label study, 213 patients who previously derived benefit from first-line anti-EGFR therapy without RAS or BRAF mutations detected in ctDNA ≥ 1 year after receiving anti-EGFR-free treatment were randomized on a 1-to-1 basis to receive panitumumab plus regorafenib either after progression (arm A, n = 106) or reverse sequence (arm B, n = 107). The primary end point was overall survival (OS). Key secondary end points included objective response rate (ORR), duration of response, and progression-free survival (PFS).
At a median follow-up of 31.9 months, median OS was 11.6 months in arm A and 11.7 months in arm B (hazard ratio [HR] 1.13; 85% confidence interval [CI], 0.90 to 1.41; P = .441). Post-study treatment was administered to 51% and 44% of patients, respectively. Subgroup analysis results revealed that shorter OS was reported in patients with an EGFR-free interval of ≤ 6 months (P = .041) in arm A. Higher ORR, disease control rate, and PFS was observed with panitumumab regardless of treatment sequence
“Anti-EGFR [retreatment] is an option in the continuum-of-care of chemorefractory mCRC [patients] with RAS and BRAF [wild-type] tumors, with no alterations of acquired resistance in their ctDNA,” concluded Dr Germani et al. “A clearly better [treatment] sequence was not identified, except for the subgroup of [patients] with an anti-EGFR-free interval ≤ 6 [months] where the [regorafenib]-first sequence seems preferable.”
Source:
Germani MM, Ciraci P, Piertrantonio 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): Final results of the randomized PARERE trial by GONO. Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA32
