Oncology Department, Geneva University Hospital, Geneva, Switzerland.
Oncology Department, Geneva University Hospital, Geneva, Switzerland
Cancer Genomics Proteomics. 2020 Sep-Oct;17(5):597-603. doi: 10.21873/cgp.20216.
BACKGROUND/AIM: Non-small cell lung cancer (NSCLC) patients with activating somatic mutations in the epidermal growth factor receptor (EGFR) have better outcomes with tyrosine kinase inhibitors (TKIs) than with chemotherapy. However, even with the most effective therapies, not all patients respond. The presence of concurrent pathogenic mutations could play a role in resistance. The objective of this study was to analyze the impact of concurrent mutations in genes other than EGFR on survival outcomes of patients treated with TKIs for EGFR-mutated NSCLC.
We conducted a retrospective cohort analysis of patients with advanced NSCLC treated with TKIs in our center between January 2016 and December 2019. Clinical and pathological characteristics, EGFR mutational status, presence of co-occurring genetic alterations, overall (OS) and progression-free survival (PFS) were evaluated.
Of the 42 patients with advanced NSCLC harboring EGFR mutations who received TKIs in our center, 22 (52%) had no concurrent mutations, 15 (36%) had a non-pathogenic, non-resistance co-mutation, and 5 (12%) had a concurrent resistance mutation. The median OS of the global population was 14.9 months, with a shorter OS in the group harboring a concurrent resistance mutation (7.7 vs. 18.1 months, p=0.002). Concurrent mutations possibly associated with resistance were found in PIK3CA, KRAS and PTEN genes.
Concurrent resistance mutations in genes other than EGFR influenced the outcome of patients with NSCLC, while non-resistance mutations did not alter survival, compared to the absence of co-mutations. This evidence highlights the importance of a careful interpretation of molecular findings. The best treatment options for these patients should be studied in randomized controlled trials.
背景/目的：与化疗相比，表皮生长因子受体（EGFR）激活体细胞突变的非小细胞肺癌（NSCLC）患者使用酪氨酸激酶抑制剂（TKI）的效果更好。然而，即使使用最有效的疗法，并非所有患者都有反应。同时存在致病性突变可能在耐药性中起作用。本研究的目的是分析除 EGFR 以外的其他基因同时发生突变对接受 EGFR 突变 NSCLC 患者 TKI 治疗的生存结果的影响。
我们对 2016 年 1 月至 2019 年 12 月在我们中心接受 TKI 治疗的晚期 NSCLC 患者进行了回顾性队列分析。评估了临床和病理特征、EGFR 突变状态、共存遗传改变的存在、总生存期（OS）和无进展生存期（PFS）。
在我们中心接受 TKI 治疗的 42 例晚期 NSCLC 患者中，22 例（52%）无同时发生突变，15 例（36%）存在非致病性、非耐药性共突变，5 例（12%）存在同时发生的耐药性突变。总体人群的中位 OS 为 14.9 个月，携带同时发生的耐药性突变的组 OS 更短（7.7 与 18.1 个月，p=0.002）。在 PIK3CA、KRAS 和 PTEN 基因中发现了可能与耐药性相关的同时发生的突变。
除 EGFR 以外的基因中的同时发生的耐药性突变影响 NSCLC 患者的结局，而非耐药性突变与无共突变相比并未改变生存。这一证据强调了仔细解释分子发现的重要性。应在随机对照试验中研究这些患者的最佳治疗选择。
