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。