Response to crizotinib + regorafenib + PD-1 inhibitor in a metastatic BRAF V600E MT colon cancer patients with acquired C-MET amplification and TPM4- ALK fusion: case report and review of literature

Abstract Colorectal cancer (CRC) with BRAFV600E CRC had a relatively poor prognosis. We report the case of a 49-year-old Chinese male was diagnosed asascending colon adenocarcinoma (cT3N+?M1) with liver metastases. The patient performed next-generation sequencing(NGS) using tissue and circulating tumor DNA (ctDNA), and the results showed a BRAFV600E mutation. He received an initial combination treatment with cetuximab, darafenib, and trametinib with a partial response (PR) assessment. We changed the therapy regimen on this patient several times because of the patient's intolerance to the drugs or the inefficacy of the treatment. During this period, we detected the c-MET amplification and TPM4-ALK fusion by NGS after triplet targeted therapy (tislelizumab, darafenib, and trametinib), thus he was finally treated with PD-1 inhibitor (Tislelizumab), MET/ALK inhibitor (Crozitinib) plus BRAF inhibitor (regorafenib). Imageological examinations showed that PR was achieved and ctDNA sequencing results indicated a significantly reduced BRAF mutation frequency, MET amplification and TPM4-ALK fusion were undetectable. This study reported a co-existence of a BRAFV600E mutation, c-MET amplification and TPM4-ALK fusion in a CRC patient. Administration of crizotinib combined with regorafenib and Tislelizumab obtained an obvious response. Furthermore, continuous ctDNA detection appears to be a promising technique to monitor tumor burden, which may provide better clinical decision support during the disease course.