Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego Moores Cancer Center, La Jolla, CA, USA.
Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea.
Mol Oncol. 2022 Jul;16(13):2575-2584. doi: 10.1002/1878-0261.13202. Epub 2022 Apr 8.
Treatment for advanced colorectal cancer is often limited by complex molecular profiles, which promote resistance to systemic agents and targeted monotherapies. Recent studies suggest that a personalized, combinatorial approach of matching drugs to tumor alterations may be more effective. We implemented a precision medicine strategy by forming a Molecular Tumor Board (MTB), a multidisciplinary team of clinicians, scientists, bioinformaticians and geneticists. The MTB integrated molecular profiling information and patient characteristics to develop N-of-One treatments for 51 patients with advanced colorectal cancer. All patients had metastatic disease and 63% had received ≥ 3 prior therapy lines. Overall, 34/51 patients (67%) were matched to ≥ 1 drug recommended by the MTB based on individual tumor characteristics, whereas 17/51 (33%) patients received unmatched therapies. Patients who received matched therapy demonstrated significantly longer progression-free survival (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.21-0.81; P = 0.01) and a trend towards higher clinical benefit rates (41% vs. 18%, P = 0.058) (all multivariate) compared to patients receiving unmatched therapy. The MTB facilitated personalized matching of drugs to tumor characteristics, which was associated with improved progression-free survival in patients with advanced colorectal cancer.
晚期结直肠癌的治疗常常受到复杂分子谱的限制，这些谱促进了对全身药物和靶向单药治疗的耐药性。最近的研究表明，针对肿瘤改变的个性化、组合药物匹配方法可能更有效。我们通过组建一个分子肿瘤委员会（MTB）来实施精准医学策略，这是一个由临床医生、科学家、生物信息学家和遗传学家组成的多学科团队。MTB 整合了分子谱信息和患者特征，为 51 名晚期结直肠癌患者制定了 N-of-One 治疗方案。所有患者均患有转移性疾病，63%的患者接受了≥3 线既往治疗。总体而言，根据个体肿瘤特征，34/51 名患者（67%）与 MTB 推荐的≥1 种药物匹配，而 17/51 名患者（33%）接受了不匹配的治疗。接受匹配治疗的患者无进展生存期显著延长（风险比 [HR]，0.41；95%置信区间 [CI]，0.21-0.81；P=0.01），且临床获益率（41% vs. 18%）也有升高趋势（均为多变量），与接受不匹配治疗的患者相比。MTB 促进了药物与肿瘤特征的个性化匹配，这与晚期结直肠癌患者无进展生存期的改善相关。
