Department of Oncology, Oncology Unit, University of Torino, San Luigi Gonzaga Hospital, Orbassano, Italy.
Department of Oncology, Pathology Unit, University of Torino, San Luigi Gonzaga Hospital, Orbassano, Italy.
Cancer. 2023 Jun 1;129(11):1662-1671. doi: 10.1002/cncr.34731. Epub 2023 Mar 11.
KRAS mutation-positive (KRAS-positive), advanced nonsmall-cell lung cancer (NSCLC) is characterized by a poor prognosis. KRAS mutations are extremely heterogeneous from a biologic point of view, and real-world data by mutation subtype in the era of immunotherapy are still incomplete.
The objective of this study was to retrospectively analyze all consecutive patients with advanced/metastatic, KRAS-positive NSCLC who were diagnosed at a single academic institution since the advent of immunotherapy. The authors report on the natural history of the disease as well as the efficacy of first-line treatments in the entire cohort and by KRAS mutation subtypes as well as the presence/absence of co-mutations.
From March 2016 to December 2021, the authors identified 199 consecutive patients who had KRAS-positive, advanced or metastatic NSCLC. The median overall survival (OS) was 10.7 months (95% confidence interval [CI], 8.5-12.9 months), and there were no differences by mutation subtype. Among 134 patients who received first-line treatment, the median OS was 12.2 months (95% CI, 8.3-16.1 months), and the median progression-free survival was 5.6 months (95% CI, 4.5-6.6 months). At multivariate analysis, only an Eastern Cooperative Oncology Group performance status of 2 was associated with significantly shorter progression-free survival and OS.
KRAS-positive, advanced NSCLC is characterized by a poor prognosis despite the introduction of immunotherapy. Survival was not associated with KRAS mutation subtype.
This study evaluated the efficacy of systemic therapies for advanced/metastatic nonsmall cell lung cancer harboring KRAS mutations, along with the potential predictive and prognostic role of mutation subtypes. The authors found that advanced/metastatic, KRAS-positive nonsmall cell lung cancer is characterized by a poor prognosis and that first-line treatment efficacy is not related to different KRAS mutations, although a numerically shorter median progression-free survival was observed in patients who had p.G12D and p.G12A mutations. These results underline the need for novel treatment options in this population, such as next-generation KRAS inhibitors, which are in clinical and preclinical development.
KRAS 突变阳性（KRAS 阳性）的晚期非小细胞肺癌（NSCLC）的预后较差。从生物学角度来看，KRAS 突变非常具有异质性，免疫治疗时代的真实世界数据按突变亚型仍不完全。
本研究旨在回顾性分析自免疫治疗问世以来，在一家学术机构诊断的所有连续的 KRAS 阳性、晚期/转移性 NSCLC 患者。作者报告了疾病的自然史，以及整个队列以及按 KRAS 突变亚型以及有无共突变的一线治疗的疗效。
从 2016 年 3 月至 2021 年 12 月，作者确定了 199 名连续的 KRAS 阳性、晚期或转移性 NSCLC 患者。中位总生存期（OS）为 10.7 个月（95%置信区间 [CI]，8.5-12.9 个月），且无突变亚型差异。在 134 名接受一线治疗的患者中，中位 OS 为 12.2 个月（95%CI，8.3-16.1 个月），中位无进展生存期为 5.6 个月（95%CI，4.5-6.6 个月）。多变量分析显示，仅东部肿瘤协作组（ECOG）体能状态 2 与明显较短的无进展生存期和 OS 相关。
尽管免疫治疗已经问世，但 KRAS 阳性的晚期 NSCLC 仍具有较差的预后。生存与 KRAS 突变亚型无关。
普通语言摘要：本研究评估了针对 KRAS 突变的晚期/转移性非小细胞肺癌的系统治疗疗效，以及突变亚型的潜在预测和预后作用。作者发现，晚期/转移性 KRAS 阳性非小细胞肺癌的预后较差，并且一线治疗的疗效与不同的 KRAS 突变无关，尽管在具有 p.G12D 和 p.G12A 突变的患者中观察到中位无进展生存期略短。这些结果强调了在这一人群中需要新的治疗选择，例如正在临床和临床前开发的下一代 KRAS 抑制剂。
