Sharett institute of Oncology, Hebrew University-Hadassah Medical Center, Jerusalem, 91120, Israel.
Foundation Medicine Inc, Cambridge, MA, United States.
Lung Cancer. 2019 Nov;137:48-51. doi: 10.1016/j.lungcan.2019.09.008. Epub 2019 Sep 12.
Identifying new predictive biomarkers in lung cancer that will prolong survival for additional subgroups of patients is of utmost importance. We report response to treatment and survival among homologous recombination deficient (HRD) lung cancer patients mostly BRCA mutation carriers to better define the predictive value of HRD status among non-small cell lung cancer (NSCLC).
We retrospectively evaluated our genetic and pathology database and identified 14 carriers of germline mutation in BRCA1 (n = 5), BRCA2 (n = 8), or PALB2 (n = 1) and a patient with a somatic BRCA2 mutation. Platinum compounds were part of the initial or follow-on treatment protocols in 9/11 with metastatic disease. Overall survival (OS) and response to platinum were analyzed in these patients.
Median OS for the 11 patients was 30 months. The 2- and 3-year survival rates in our cohort were 62.5% and 28.6%, respectively, and 7/10 patients with metastatic lung cancer survived for more than 1 year which compares favorably with the literature. Of eight patients who were treated with platinum compounds, seven responded; however, in two the response endured for <6 months. The Foundation Medicine LOH/HRD genomic score was calculated in three patients and the level was high in 2/3 (66%), including 1/2 tumors in germline BRCA mutation carriers and tumor in the patient with a somatic BRCA2 mutation. In both complete response to platinum was recorded.
Response rate to platinum compounds and survival in these patients do suggest that platinum-based therapies should still be incorporated in our treatment regimen for the patients with HRD lung cancer, and that BRCA and other HRR associated gene testing may be important in lung cancer patients.
鉴定肺癌新的预测性生物标志物，使更多亚组患者的生存时间延长，这一点至关重要。我们报告了同源重组缺陷（HRD）肺癌患者（主要为 BRCA 突变携带者）的治疗反应和生存情况，以更好地确定 HRD 状态在非小细胞肺癌（NSCLC）中的预测价值。
我们回顾性地评估了我们的遗传和病理数据库，确定了 14 名携带 BRCA1（n=5）、BRCA2（n=8）或 PALB2（n=1）种系突变的患者和 1 名体细胞 BRCA2 突变患者。在 11 名转移性疾病患者中，铂类化合物是初始或后续治疗方案的一部分。对这些患者的总生存期（OS）和对铂类药物的反应进行了分析。
11 名患者的中位 OS 为 30 个月。本队列的 2 年和 3 年生存率分别为 62.5%和 28.6%，10 名转移性肺癌患者中有 7 名存活时间超过 1 年，这与文献相比是有利的。在接受铂类化合物治疗的 8 名患者中，有 7 名患者有反应；然而，其中 2 名患者的反应持续时间<6 个月。在 3 名患者中计算了 Foundation Medicine LOH/HRD 基因组评分，其中 2/3（66%）水平较高，包括 2 名种系 BRCA 突变携带者的肿瘤和 1 名体细胞 BRCA2 突变患者的肿瘤。在这两名患者中均观察到对铂类的完全反应。
这些患者对铂类化合物的反应率和生存率确实表明，对于 HRD 肺癌患者，铂类为基础的治疗仍应纳入我们的治疗方案，BRCA 和其他 HRR 相关基因检测在肺癌患者中可能很重要。
