【摘要号：MO40-6】encorafenib联合西妥昔单抗和binimetinib治疗BRAF V600E突变转移性结直肠癌的临床预后

BEACON CRC研究证明了encorafenib联合西妥昔单抗治疗BRAF V600E突变转移性结直肠癌（mCRC）患者的临床疗效。本研究旨在通过全面的分子分析，以确定联合方案治疗BRAF V600E突变mCRC的疗效决定因素。

背景

方法

我们调查了2018年4月至2023年5月在国家癌症中心医院东区接受encorafenib、binimetinib和西妥昔单抗（三联方案）或encorafenib和binimetinib（双联方案）治疗的BRAF V600E突变mCRC患者的临床预后。

本研究纳入58例患者，其中45例患者接受三联方案治疗，13例患者接受双联方案治疗。41例患者既往接受过一线治疗，17例患者既往接受过二线或更多线治疗。5例患者表现出MSI-H/dMMR状态。

总体患者客观缓解率为37.9%（三联方案为42.2%，二联方案为23.1%），疾病控制率为81.0%（三联方案为84.4%，二联方案为69.2%）。中位无进展生存期和总生存期分别为5.3个月（三联方案为5.4个月，双联方案为4.9个月）和10.8个月（三联方案10.5个月，双联方案为20.5个月）。

5例MSI-H/dMMR患者均接受了抗PD-1治疗，其中3例患者的无进展生存期比encorafenib联合西妥昔单抗联合或不联合binimetinib的患者更长。

结果

结论

在BRAF V600E突变的mCRC中，encorafenib联合西妥昔单抗加或不加binimetinib的临床预后与关键试验中的结果一致。

MO40-5

Impact of early tumor shrinkage and depth of response in patients with BRAF V600E-mutant metastatic colorectal cancer

Background

Early tumor shrinkage (ETS) and the depth of response (DpR) are early on-treatment surrogate markers for survival in patients with metastatic colorectal cancer (mCRC). However, the utility of ETS and DpR for BRAF V600E mutant (MT) mCRC which has a poor prognosis remains unclear. The aim of this study is to evaluate the association between ETS and DpR and clinical outcomes in BRAF V600E MT mCRC.

Methods

mCRC patients who were diagnosed BRAF V600E MT and treated with 1st line chemotherapy from June 2011 to March 2023 at single cancer institute were enrolled. We analyzed the association between ETS and DpR and clinical outcome. Subgroup analysis of clinical factors related to progression free survival (PFS) and overall survival (OS) was performed using multivariate analysis.

Results

In total, 54 patients of BRAF V600E MT mCRC had at least one target lesion. Patients with ETS ≥ 20% and DpR ≥ 25% (median value) were 24 (44.4%) and 27 (50%) respectively. PFS was 7.5 months (95% confidence interval (CI), 5.0-9.9) and OS was 17.1 months (95% CI, 11.7-20.2). Patients with ETS ≥ 20% had longer PFS and tended to have longer OS than those with non-ETS, with a median PFS of 9.8 months vs. 4.8 months (P = 0.048, hazard ratio (HR), 0.55; 95% CI, 0.30-1.00), and a median OS of 22.6 months vs. 11.6 months (P = 0.18, HR, 0.67; 95% CI, 0.37-1.21). Patients with DpR ≥ 25% had also longer PFS and OS than those with non-DpR, with a median PFS of 11.0 vs. 4.3 months (P < 0.01, HR, 0.36; 95% CI, 0.20-0.66) and a median OS of 22.6 vs. 10.1 months (P = 0.047, HR, 0.55; 95% CI, 0.31-1.00). In multivariate analysis, DpR was significantly associated with both longer PFS (HR: 0.27, 95% CI: 0.14–0.55, P < 0.01) and OS (HR: 0.52, 95% CI: 0.29–0.96, P = 0.04).

Conclusions

ETS and DpR may be early surrogate markers for clinical outcome in BRAF V600E MT mCRC who were treated with 1st line chemotherapy.

MO40-6

Clinical outcome of encorafenib, cetuximab and binimetinib in BRAF V600E-mutated metastatic colorectal cancer

Background

BEACON CRC trial demonstrated the clinical efficacy of encorafenib plus cetuximab with or without binimetinib in patients with BRAF V600E-mutated metastatic colorectal cancer (mCRC). This study aimed to perform a comprehensive molecular analysis to identify determinants of responsiveness to the combination therapy in BRAF V600E-mutated mCRC.

Methods

We investigated clinical outcome in patients with BRAF V600E-mutated mCRC who received encorafenib, binimetinib and cetuximab (triplet) or encorafenib and binimetinib (doublet) at National Cancer Center Hospital East from April 2018 to May 2023.

Results

Fifty-eight patients (45 with triplet and 13 doublet) were included in this study. Forty-one patients had received one prior line of therapy, while 17 patients had received two or more prior lines of therapy. Five patients exhibited MSI-high or dMMR status. The objective response rate was 37.9% (42.2% with triplet and 23.1% with doublet) and the disease control rate was 81.0% (84.4% with triplet and 69.2% with doublet). The median progression-free survival and overall survival were 5.3 months (5.4 months with triplet and 4.9 months with double) and 10.8 months (10.5 months with triplet and 20.5 months with doublet), respectively. All five patients with MSI-high or dMMR received anti-PD-1 therapy, with three of them showed longer progression-free survival compared with that of encorafenib plus cetuximab with or without binimetinib.

Conclusion

Clinical outcomes of encorafenib plus cetuximab with or without binimetinib in BRAF V600E-mutated mCRC were comparable to those in the pivotal trial. Biomarker analysis including whole-exome sequencing, RNA sequencing consensus, molecular subtypes and multiplex fluorescence immunohistochemistry will be presented at the meeting.

（来源：肿瘤瞭望-消化时讯）

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