Rechallenge with Anti-EGFR Treatment in RAS/BRAF wt Metastatic Colorectal Cancer (mCRC) in Real Clinical Practice: Experience of the GITuD Group.

IF 4.4 3区医学 Q2 ONCOLOGY Targeted Oncology Pub Date : 2024-07-01 Epub Date: 2024-05-23 DOI:10.1007/s11523-024-01062-z

Mercedes Salgado Fernández, Margarita Reboredo López, Marta Covela Rúa, Sonia Candamio, Paula González-Villarroel, Luis Felipe Sánchez-Cousido, Begoña Graña, Alberto Carral-Maseda, Soledad Cameselle-García, Vanesa Varela Pose, Maria Elena Gallardo-Martín, Nieves Martínez-Lago

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Abstract

Background: There are few third- and fourth-line therapeutic options for metastatic colorectal cancer (mCRC). In RAS/BRAF wild-type (wt) mCRC previously treated with anti-epidermal growth factor receptor (anti-EGFR) (first-line) and relapsed after a good response, retreatment with anti-EGFR (rechallenge) emerges as a therapeutic alternative.

Objective: The aim was to show the activity and safety of anti-EGFR rechallenge in RAS/BRAF wt mCRC in real-world practice.

Patients and methods: A multicenter, retrospective, observational study (six hospitals of the Galician Group of Research in Digestive Tumors) was conducted. Adult patients with RAS/BRAF wt mCRC, evaluated by liquid biopsy, were included. They received anti-EGFR rechallenge (cetuximab, panitumumab) as monotherapy, or combined with chemotherapy, in third- or subsequent lines. Efficacy (overall response rate [ORR], disease control rate [DCR], overall survival [OS], and progression-free survival [PFS]) and safety (incidence of adverse events [AEs]) were assessed.

Results: Thirty-one patients were analyzed. Rechallenge (median 6 cycles [range 1-27], mainly cetuximab [80.7%]), started at a median anti-EGFR-free time of 18.4 months (1.7-37.5 months) after two (38.7%) or more (61.3%) lines of treatment; 64.5% of patients received a full dose. Median OS and PFS were 9.8 months (95% confidence interval [CI] 8.2-11.4) and 2.6 months (95% CI 1.7-3.4), respectively. ORR was 10%, and DCR was 30%. The most common AEs were diarrhea (35.5%), anemia (29%), emesis (6.4%), and neutropenia (6.4%); < 5% grade ≥ 3; 48.4% of patients reported anti-EGFR-related skin toxicity (grade > 1). Hypomagnesemia required supplements in 29% of patients. Dose delays (≥ 3 days) and reduction (≥ 20%) were reported in 11 (35.5%) and seven patients (22.6%), respectively.

Conclusions: In RAS/BRAF wt mCRC patients, an anti-EGFR rechallenge provides a feasible therapeutic option with clinical benefit (survival) and a manageable safety profile.

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在实际临床实践中对 RAS/BRAF wt 转移性结直肠癌 (mCRC) 进行抗 EGFR 治疗的再挑战：GITuD小组的经验。

背景：转移性结直肠癌（mCRC）的三线和四线治疗方案很少。对于曾接受过抗表皮生长因子受体（anti-EGFR）治疗（一线）并在良好反应后复发的RAS/BRAF野生型（wt）mCRC，抗EGFR再治疗（再挑战）成为一种治疗选择：患者和方法：一项多中心、回顾性、前瞻性研究发现，在RAS/BRAF wt mCRC患者中，抗EGFR再治疗的活性和安全性在实际应用中得到了验证：进行了一项多中心、回顾性、观察性研究（加利西亚消化系统肿瘤研究小组的六家医院）。研究纳入了通过液体活检评估的RAS/BRAF wt mCRC成人患者。他们接受了抗表皮生长因子受体再挑战（西妥昔单抗、帕尼单抗）单药治疗，或在第三线或后续治疗中联合化疗。对疗效（总反应率[ORR]、疾病控制率[DCR]、总生存期[OS]和无进展生存期[PFS]）和安全性（不良反应发生率[AEs]）进行了评估：对31名患者进行了分析。再挑战（中位 6 个周期[范围 1-27]，主要是西妥昔单抗[80.7%]）开始于两线（38.7%）或更多线（61.3%）治疗后的中位无抗 EGFR 时间 18.4 个月（1.7-37.5 个月）；64.5% 的患者接受了全剂量治疗。中位OS和PFS分别为9.8个月（95% 置信区间[CI] 8.2-11.4）和2.6个月（95% CI 1.7-3.4）。ORR为10%，DCR为30%。最常见的不良反应为腹泻（35.5%）、贫血（29%）、呕吐（6.4%）和中性粒细胞减少（6.4%）；1）。29%的患者需要补充低镁血症。分别有 11 例（35.5%）和 7 例（22.6%）患者的剂量延迟（≥ 3 天）和减少（≥ 20%）：在RAS/BRAF wt mCRC患者中，抗EGFR再挑战提供了一种可行的治疗方案，具有临床获益（生存期）和可控的安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Targeted Oncology 医学-肿瘤学

CiteScore

8.40

自引率

3.70%

发文量

审稿时长

>12 weeks

期刊介绍： Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes: Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches. Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways. Current Opinion articles that place interesting areas in perspective. Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations. Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement. Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.