Efficacy of regorafenib and 5-fluorouracil-based rechallenge treatment in the third-line treatment of metastatic colorectal cancer: A Turkish oncology group study.

202 Background: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib (Reg) revealed promising results by improving overall survival compared to best supportive care. However, in real-world practice rechallenge chemotherapy (CTr) is often preferred even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. Methods: In this retrospective multi-institutional trial, mCRC patients from 21 centers in Turkey progressing after 2 lines of chemotherapy between 2012-2020 were analyzed. Patients who were treated with Reg or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. Overall survival (OS), objective response rate (ORR), progression free survival (PFS) and toxicity were analyzed. Chi-square, Kaplan-Meier method and Cox regression analysis were used for analysis. Results: The clinical data of 441 mCRC patients were analyzed. Of these, 284 received regorafenib while 156 received rechallenge chemotherapy. The mean age was 57 and 56% was male. Median OS since the diagnosis was better with CTr than with Reg (48 months (95% CI, 43.4–52.6) vs. 39 months (95% CI, 35.4–42.5), p<0.001). Median OS after the third-line treatment was 12.0 (95% CI, 9.9–14) and 9.0 months (95% CI, 7.5–10.4) for CTr and Reg groups, respectively (p<0.001). PFS was 6 months for patients receiving CTr and 4 months for those treated with Reg (p = 0.139). ORR was significantly higher in CTr group than Reg (p<0.001). BRAF status, MSI status and treatment type (CTr vs. Reg) are factors found associated with OS in Cox regression analysis (p<0.001, p=0.021 and p<0.001, respectively). Adverse effects were seen in 82% and 68.2% of patients receiving Reg and CTr, respectively. Discontinuation of treatment due to adverse effects was higher in patients treated with Reg (10% vs. 2.5%). Conclusions: Our analysis revealed that rechallenge is an appreciated option, in both efficacy and toxicity, when the limited treatment options for mCRC is considered. Although regorafenib treatment contributes to survival, CTr shows better disease control. Our study has the highest number of patients in the literature. Still, prospective studies are mandatory for validation of CTr in the third-line treatment of mCRC.