Hafliger Emilie, Boccaccino Alessandra, Lapeyre-Prost Alexandra, Perret Audrey, Gallois Claire, Antista Maria, Pilla Lorenzo, Lecomte Thierry, Scartozzi Mario, Soularue Emilie, Salvatore Lisa, Bourgeois Vincent, Salati Massimiliano, Tougeron David, Evesque Ludovic, Vaillant Jean-Nicolas, El-Khoury Reem, Lonardi Sara, Cremolini Chiara, Taieb Julien
Department of Gastroenterology and Digestive Oncology, SIRIC CARPEM, Georges-Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP-Paris Centre), Université de Paris, Paris France.
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy.
Eur J Cancer. 2022 Jun;168:34-40. doi: 10.1016/j.ejca.2022.03.011. Epub 2022 Apr 15.
Encorafenib plus cetuximab is efficient in anti-EGFR-naïve patients with BRAF mutated (BRAFm) metastatic colorectal cancer (mCRC). No data are available concerning the efficacy of BRAF inhibitors associated with anti-EGFRs (B + E) in patients previously treated with an anti-EGFR agent.
We retrospectively collected a series of patients with BRAFm mCRC treated with B + E after previous anti-EGFR treatment, in 14 centers. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of treatment, and we reported objective response and disease control rates (ORR, DCR; RECIST V1.1).
Twenty-five BRAFm mCRC patients were enrolled. Prior to B + E treatment, 4/10/11 patients were treated with 1/2/> 2 previous treatment lines. Ten patients received previous panitumumab, 14 cetuximab, 1 both. Immediate progression with previous anti-EGFR was reported for 7 patients. Anti-BRAF was encorafenib for 21 patients, dabrafenib for 4 patients, with cetuximab for 24 patients and panitumumab for 1 patient. ORR was 40% (10 patients) and DCR was 80% (20 patients). Median PFS and OS were 4.8 months (95% CI, 4.01-7.95) and 10.1 months (95% CI, 7.75-NR). DCR amongst patients with previous primary resistance to anti-EGFR (N = 7) was 100%. Two patients discontinued B + E due to drug-related adverse event.
Though in a limited retrospective series of patients, these results show the efficacy of the combination of anti-BRAF and anti-EGFRs in BRAFm mCRC patients previously treated with an anti-EGFR. The use of this combination should thus not be ruled out in this population with limited therapeutic options.
恩考芬尼联合西妥昔单抗对初治的BRAF突变（BRAFm）转移性结直肠癌（mCRC）患者有效。关于BRAF抑制剂联合抗表皮生长因子受体（anti-EGFR）药物（B+E）在既往接受过抗EGFR药物治疗的患者中的疗效，尚无相关数据。
我们回顾性收集了14个中心既往接受过抗EGFR治疗后接受B+E治疗的一系列BRAFm mCRC患者。从治疗开始计算无进展生存期（PFS）和总生存期（OS），并报告客观缓解率和疾病控制率（ORR、DCR；实体瘤疗效评价标准第1.1版）。
共纳入25例BRAFm mCRC患者。在接受B+E治疗前，4/10/11例患者接受过1/2/＞2线既往治疗。10例患者既往接受过帕尼单抗治疗，14例接受过西妥昔单抗治疗，1例两者均接受过。7例患者报告在既往抗EGFR治疗后立即出现疾病进展。21例患者使用的抗BRAF药物为恩考芬尼，4例为达拉非尼，24例联合西妥昔单抗，1例联合帕尼单抗。ORR为40%（10例患者），DCR为80%（20例患者）。中位PFS和OS分别为4.8个月（95%CI，4.01-7.95）和10.1个月（95%CI，7.75-未达到）。既往对抗EGFR原发性耐药的患者（n=7）中DCR为100%。2例患者因药物相关不良事件停用B+E。
尽管本研究为有限的回顾性患者系列，但这些结果显示了抗BRAF与抗EGFR联合用药在既往接受过抗EGFR治疗的BRAFm mCRC患者中的疗效。因此，在这个治疗选择有限的人群中，不应排除使用这种联合治疗方案。
