Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego Moores Cancer Center, La Jolla, CA.
Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Diego Moores Cancer Center, La Jolla, CA.
JCO Precis Oncol. 2022 Jan;6:e2000508. doi: 10.1200/PO.20.00508.
Next-generation sequencing is increasingly used in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide matched therapy; however, outcome data are limited. We evaluate the effect of the degree of matching of tumors to treatment as well as compliance to MTB recommendations on outcomes.
Overall, 164 patients with consecutive gynecologic and breast cancers presented at MTB were assessed for clinicopathologic data, next-generation sequencing results, MTB recommendations, therapy received, and outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment over total pathogenic alterations, and compliance to MTB recommendations were analyzed in context of oncologic outcomes.
Altogether, 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS ≥ 40% had higher overall response rate (30.8% 7.1%; = .001), progression-free survival (PFS; hazard ratio [HR] 0.51; 95% CI, 0.31 to 0.85; = .002), and a trend toward improved overall survival (HR 0.64; 95% CI, 0.34 to 1.25; = .082) in univariate analysis. The PFS advantage remained significant in multivariate analysis (HR 0.5; 95% CI, 0.3 to 0.8; = .006). Higher MTB recommendation compliance was significantly associated with improved median PFS (9.0 months for complete; 6.0 months for partial; 4.0 months for no compliance; = .004) and overall survival (17.1 months complete; 17.8 months partial; 10.8 months none; = .046). Completely MTB-compliant patients had higher MS ( < .001). In multivariate analysis comparing all versus none MTB compliance, overall response (HR 9.5; 95% CI, 2.6 to 35.0; = .001) and clinical benefit (HR 8.8; 95% CI, 2.4 to 33.2; = .001) rates were significantly improved with higher compliance.
Compliance to MTB recommendations resulted in higher degrees of matched therapy and correlates with improved outcomes in patients with gynecologic and breast cancers.
下一代测序技术在妇科和乳腺癌中的应用日益广泛。多学科分子肿瘤委员会(MTB)可以指导匹配治疗;然而,相关数据有限。我们评估了肿瘤与治疗的匹配程度以及对 MTB 建议的遵守程度对结果的影响。
总体而言,对 164 例连续就诊于 MTB 的妇科和乳腺癌患者的临床病理数据、下一代测序结果、MTB 建议、接受的治疗和结果进行评估。在肿瘤学结果背景下,分析了匹配评分(MS),定义为治疗靶向的改变百分比与总致病性改变百分比的比值,以及对 MTB 建议的遵守程度。
共有 113 名女性在 MTB 后接受了治疗评估;54%的患者接受了匹配治疗。MS≥40%的患者总体缓解率更高(30.8%vs7.1%, =.001),无进展生存期(PFS;风险比[HR]0.51;95%CI,0.31 至 0.85; =.002)和总生存(OS)有改善趋势(HR 0.64;95%CI,0.34 至 1.25; =.082)。在单变量分析中,PFS 优势仍然显著。多变量分析显示,PFS 仍有显著改善(HR 0.5;95%CI,0.3 至 0.8; =.006)。更高的 MTB 建议遵守率与中位 PFS(完全遵守者 9.0 个月,部分遵守者 6.0 个月,不遵守者 4.0 个月; =.004)和总生存(完全遵守者 17.1 个月,部分遵守者 17.8 个月,不遵守者 10.8 个月; =.046)的改善显著相关。完全 MTB 遵守的患者 MS 更高( <.001)。在比较所有 MTB 与无 MTB 依从性的多变量分析中,总缓解率(HR 9.5;95%CI,2.6 至 35.0; =.001)和临床获益率(HR 8.8;95%CI,2.4 至 33.2; =.001)随着依从性的提高而显著改善。
对 MTB 建议的遵守导致了更高程度的匹配治疗,与妇科和乳腺癌患者的改善结果相关。