Chan O S H, Lee V H F, Mok T S K, Mo F, Chang A T Y, Yeung R M W
Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.
Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China.
Clin Oncol (R Coll Radiol). 2017 Sep;29(9):568-575. doi: 10.1016/j.clon.2017.04.035. Epub 2017 May 9.
Almost all patients with epidermal growth factor receptor (EGFR) mutations will develop resistance to first-line EGFR tyrosine kinase inhibitors (TKIs). The management of oligoprogression on EGFR TKI is controversial. Irradiating progressing tumours may potentially eradicate the resistant clone and allow continuation of EGFR TKI, but the clinical data remain sparse. We aimed to assess the effect of radiotherapy on survival outcomes in patients with oligoprogression in a matched-cohort study.
This was a retrospective matched-cohort study comparing patients with EGFR mutation-positive stage IV non-small cell lung cancer receiving radiotherapy versus chemotherapy for progression. Patients in the radiotherapy group received radiotherapy (mainly stereotactic ablative radiotherapy) for oligoprogression, whereas the chemotherapy group received only systemic chemotherapy upon progression. Key prognostic factors including gender, age, performance status, time to first progression and mutation subtypes were matched.
Twenty-five patients with oligoprogression (radiotherapy group) were identified, and a matched chemotherapy group with the same number of patients was generated. The median duration of follow-up was 24.3 and 34 months for the radiotherapy and chemotherapy groups, respectively. The median overall survival of the radiotherapy group was significantly longer than the chemotherapy group, 28.2 versus 14.7 months (P = 0.026). The median progression-free survival (PFS) was 7.0 and 4.1 months after radiotherapy and chemotherapy, respectively (P = 0.0017). The use of radiotherapy was an independent predictive factor of overall survival and PFS in multivariate analysis. Only one patient had ≥grade 3 toxicity after radiotherapy. The frequency of secondary T790M mutation and subsequent Osimertinib exposure were similar in both groups.
Radiotherapy may effectively extend EGFR TKI therapy for patients with oligoprogression on TKI. Improved PFS and overall survival were observed, although potential biases should not be overlooked. Further randomised studies are warranted.
几乎所有表皮生长因子受体(EGFR)突变的患者都会对一线EGFR酪氨酸激酶抑制剂(TKIs)产生耐药性。EGFR-TKI治疗期间寡进展的管理存在争议。对进展性肿瘤进行放疗可能会根除耐药克隆并允许继续使用EGFR-TKI,但临床数据仍然很少。我们旨在通过一项匹配队列研究评估放疗对寡进展患者生存结局的影响。
这是一项回顾性匹配队列研究,比较接受放疗与化疗的EGFR突变阳性IV期非小细胞肺癌患者的病情进展情况。放疗组患者因寡进展接受放疗(主要是立体定向消融放疗),而化疗组患者病情进展时仅接受全身化疗。对包括性别、年龄、体能状态、首次进展时间和突变亚型在内的关键预后因素进行匹配。
确定了25例寡进展患者(放疗组),并生成了一个相同数量患者的匹配化疗组。放疗组和化疗组的中位随访时间分别为24.3个月和34个月。放疗组的中位总生存期明显长于化疗组,分别为28.2个月和14.7个月(P = 0.026)。放疗和化疗后的中位无进展生存期(PFS)分别为7.0个月和4.1个月(P = 0.0017)。在多变量分析中,放疗的使用是总生存期和PFS的独立预测因素。放疗后只有1例患者出现≥3级毒性。两组继发性T790M突变的频率和随后奥希替尼的暴露情况相似。
放疗可能有效地延长EGFR-TKI对TKI寡进展患者的治疗时间。观察到PFS和总生存期有所改善,尽管潜在偏倚不容忽视。有必要进行进一步的随机研究。