Jung Hyun Ae, Hong Min Hee, Lee Hyun Woo, Lee Kyung Hee, Kim Il Hwan, Min Young Joo, Ahn Hee Kyung, Shim Byoung Yong, Choi Yoon Hee, Lee Yun-Gyoo, Kim Jeong A, Jang Joung Soon, Shin Seong-Hoon, Park Keon Uk, Kang Jin Hyoung, Park Keunchil
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
Transl Lung Cancer Res. 2022 Jul;11(7):1369-1379. doi: 10.21037/tlcr-22-79.
Irrespective of the first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor chosen, acquired resistance to therapy is inevitable. Therefore, a key consideration when assessing therapeutic choices is the availability of subsequent treatment options following disease progression. We assessed clinical outcomes in patients who received first-line afatinib treatment with various second-line treatments including osimertinib for patients acquiring the T790M mutation.
A total of 737 mutation-positive (EGFR M+) non-small cell lung cancer (NSCLC) patients receiving first-line afatinib treatment were categorized by second-line treatment: T790M+ sequentially treated with osimertinib (cohort A, n=116); T790M- given chemotherapy or others (cohort B, n=143); patients with unknown T790M status (cohort C, n=111); and patients who were undergoing afatinib treatment at the time of data collection, were dead, had discontinued afatinib treatment due to serious adverse events or were lost to follow-up (cohort D, n=367). The primary outcomes were total time on treatment (TOT) and TOT for first-line (TOT-1) and second-line treatments (TOT-2). Secondary outcomes were objective response rates (ORR), overall survival (OS), and central nervous system (CNS) efficacy.
Median total TOT in cohorts A, B, C, and D were 35.10 months [95% confidence interval (CI): 30.09-43.53 months], 18.80 months (95% CI: 16.92-20.20 months), 12.00 months (95% CI: 10.22-14.98 months), and 42.60 months (95% CI: 30.95-59.23 months), respectively. The ORR of patients given afatinib was 75.7%. In patients with initial brain metastasis without local treatment, the CNS response rate was 67.0% and CNS progression-free survival was 24.70 months (95% CI: 19.84-33.15 months).
This study showed that sequential approach of afatinib followed by second line treatment is an effective therapeutic strategy for M+ NSCLC patients.
无论选择何种一线表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，治疗获得性耐药都不可避免。因此，评估治疗选择时的一个关键考虑因素是疾病进展后后续治疗方案的可用性。我们评估了接受一线阿法替尼治疗的患者接受包括奥希替尼在内的各种二线治疗（用于发生T790M突变的患者）后的临床结局。
共有737例接受一线阿法替尼治疗的EGFR突变阳性（EGFR M+）非小细胞肺癌（NSCLC）患者按二线治疗进行分类：T790M+患者序贯接受奥希替尼治疗（A组，n = 116）；T790M-患者接受化疗或其他治疗（B组，n = 143）；T790M状态未知的患者（C组，n = 111）；以及在数据收集时正在接受阿法替尼治疗、已死亡、因严重不良事件停止阿法替尼治疗或失访的患者（D组，n = 367）。主要结局为总治疗时间（TOT）以及一线治疗（TOT-1）和二线治疗（TOT-2）的TOT。次要结局为客观缓解率（ORR）、总生存期（OS）和中枢神经系统（CNS）疗效。
A、B、C和D组的中位总TOT分别为35.10个月[95%置信区间（CI）：30.09 - 43.53个月]、18.80个月（95%CI：16.92 - 20.20个月）、12.00个月（95%CI：10.22 - 14.98个月）和42.60个月（95%CI：30.95 - 59.23个月）。接受阿法替尼治疗患者的ORR为75.7%。在初始有脑转移且未进行局部治疗的患者中，CNS缓解率为67.0%，CNS无进展生存期为24.70个月（95%CI：19.84 - 33.15个月）。
本研究表明，阿法替尼序贯二线治疗是EGFR M+ NSCLC患者的一种有效治疗策略。
