Chemotherapy Rechallenge May Be Better Third-Line Option Than Regorafenib for Metastatic CRC

Chemotherapy rechallenge provides a greater benefit than regorafenib as third-line treatment for metastatic colorectal cancer (CRC), according to a retrospective study published in BMC Cancer.

The study included 394 patients with metastatic CRC who had disease progression after 2 lines of chemotherapy, 1 of which included 5-fuorouracil (5-FU).

For third-line therapy, patients received either regorafenib (n=266) or rechallenge with 5-FU-based chemotherapy (n=128). The median age of the overall cohort was 57 (range, 25-84) years, and 50% of the patients were women.

The proportion of female patients was higher in the rechallenge arm than in the regorafenib arm (P =.023), but there were no other significant differences between the treatment arms.

The median follow-up was 42.55 months. Patients who received chemotherapy rechallenge had a significant improvement in disease control rate (DCR). The DCR was 77% with chemotherapy and 49.5% with regorafenib (P <.001)

There was no significant difference in progression-free survival (PFS) between the treatment arms, but chemotherapy rechallenge significantly improved overall survival (OS).

The median PFS was 5.82 months with chemotherapy rechallenge and 4.01 months with regorafenib (P =.167). The median OS was 11.99 months and 8.08 months, respectively (P <.001).

In a multivariate analysis, independent predictors of longer OS were rechallenge treatment (hazard ratio [HR], 0.717; 95% CI, 0.556-0.924; P =.010), female sex (HR, 0.69; 95% CI, 0.54-0.88; P =.003), and response to both prior lines of treatment (HR, 0.428; 95% CI, 0.245-0.748; P =.003).

The researchers theorized that a possible reason for the inferior OS observed with regorafenib could be the need for dose reductions related to adverse events in this treatment arm. Sixty percent of patients in the regorafenib arm required a 50% or higher dose reduction due to intolerance.

The incidence of adverse events was significantly higher in the regorafenib arm than in the rechallenge arm — 84.2% and 65.6%, respectively (P <.001). Rates of nausea, diarrhea, mucositis, acneiform rash, and hepatotoxicity were significantly higher in the regorafenib arm, but the rate of neuropathy was higher in the rechallenge arm.

The researchers acknowledged that this study is limited by its retrospective nature. However, they concluded that, in the absence of prospective data, this study contributes “valuable” data to the literature, and “rechallenge treatment should be preferred” as a third-line option for patients with metastatic CRC.

This article originally appeared on Cancer Therapy Advisor