期刊
FRONTIERS IN ONCOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2023.1227644
关键词
colorectal cancer; immune checkpoint inhibitor; microsatellite stable; regorafenib; ErbB
类别
In this study, the efficacy and safety of regorafenib combined with PD-1 inhibitor in refractory MSS CRC were evaluated. The results showed that this combination treatment regimen is feasible and well-tolerated. ERBB2/ERBB3 mutation was identified as a potential predictive factor for treatment response.
BackgroundMicrosatellite stable (MSS) colorectal cancer (CRC) has been referred to as the cold tumor because of almost no response to anti-programmed death-1 (PD-1) antibody. A recent REGONIVO trial showed that regorafenib plus nivolumab had an encouraging efficacy in MSS metastatic CRC (mCRC). However, only a small subset of patients may benefit from the combination therapy. We aim to evaluate the efficacy and safety data of immune checkpoint inhibitors combined with regorafenib in refractory MSS mCRC and to discover biomarkers that can effectively stratify the beneficial patient population.MethodsWe retrospectively analyzed patients with MSS mCRC who received regorafenib combined with anti-PD-1 antibody therapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and status of gene mutation were reviewed and evaluated.ResultsTwenty-one patients received combination treatment. At a median treatment duration of 4 months, one patient achieved complete response, three patients achieved partial response, and two patients achieved stable disease as the best response. The ORR and DCR were 19% and 28.5% in the overall population, respectively. The median PFS was 4 months, and the median OS was 25 months. Only erbb2 receptor tyrosine kinase 2/erbb3 receptor tyrosine kinase 3 (ERBB2/ERBB3) mutation status was confirmed to be a potential predictive factor for effective treatment. In patients with ERBB2/ERBB3 mutation, ORR, DCR, and PFS exhibited significant improvements in comparison with that in wild-type patients. Grade 3 or higher treatment-related adverse events occurred in three patients (14.3%).ConclusionsRegorafenib in combination with PD-1 inhibitor provides a feasible treatment regimen for refractory MSS mCRC with tolerated toxicity. Patients with ERBB2/ERBB3 mutation may be the preferred population for this combination regimen.
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