Osimertinib in poor performance status patients with T790M-positive advanced non-small-cell lung cancer after progression of first- and second-generation EGFR-TKI treatments (NEJ032B).
Osimertinib in poor performance status patients with T790M-positive advanced non-small-cell lung cancer after progression of first- and second-generation EGFR-TKI treatments (NEJ032B).
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DOI：
10.1007/s10147-021-02043-2
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发表时间：
2022-01
影响因子：
3.3
通讯作者：
Isobe T
中科院分区：
文献类型：
--
作者：
Tsubata Y;Watanabe K;Saito R;Nakamura A;Yoshioka H;Morita M;Honda R;Kanaji N;Ohizumi S;Jingu D;Nakagawa T;Nakazawa K;Mouri A;Takeuchi S;Furuya N;Akazawa Y;Miura K;Ichihara E;Maemondo M;Morita S;Kobayashi K;Isobe T
奥希替尼对于 T790M 突变阳性、对表皮生长因子受体 (EGFR) 酪氨酸激酶抑制剂 (TKI) 耐药的晚期非小细胞肺癌 (NSCLC) 患者有效。然而，其对于体能状态（PS）较差的患者的有效性和安全性尚不清楚。入组患者在接受吉非替尼、厄洛替尼或阿法替尼治疗后出现疾病进展； T790M突变； IIIB、IV 期或疾病复发； PS为2-4。奥西替尼口服给药剂量为 80 毫克/天。这项 II 期研究（注册，jRCTs061180018）的主要终点是缓解率，次要终点是无进展生存期 (PFS)、总生存期 (OS)、疾病控制率和安全性。 33 名患者入组，其中 69.7% 和 24.2% 的 PS 分别为 2 和 3。一名患者因违反方案而被排除；其余32名患者的有效率为53.1%；疾病控制率为75.0%； PFS 为 5.1 个月；操作系统为 10.0 个月。最常见的 3 级或更高严重程度的不良事件是淋巴细胞减少（12.1%）。所有级别和 3-5 级的患者中，分别有 15.2% (5/33) 和 6.1% (2/33) 出现间质性肺疾病 (ILD)。一名患者因 ILD 导致治疗相关死亡。给予奥希替尼后激活 EGFR 突变呈阴性的患者的中位 PFS 比这些突变呈阳性的患者更长。奥希替尼对 EGFR-TKI 耐药、PS 较差、T790M 突变阳性晚期 NSCLC 患者足够有效。 TKI 治疗后血浆 EGFR 突变清除率可以预测对 EGFR-TKI 的反应。
Osimertinib is effective in patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, its effectiveness and safety in patients with poor performance status (PS) are unknown. Enrolled patients showed disease progression after treatment with gefitinib, erlotinib, or afatinib; T790M mutation; stage IIIB, IV, or recurrent disease; and PS of 2–4. Osimertinib was orally administered at a dose of 80 mg/day. The primary endpoint of this phase II study (registration, jRCTs061180018) was response rate and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety. Thirty-three patients were enrolled, of which 69.7% and 24.2% had PS of 2 and 3, respectively. One patient was excluded due to protocol violation; in the remaining 32 patients, the response rate was 53.1%; disease control rate was 75.0%; PFS was 5.1 months; and OS was 10.0 months. The most frequent adverse event of grade 3 or higher severity was lymphopenia (12.1%). Interstitial lung disease (ILD) was observed at all grades and at grades 3–5 in 15.2% (5/33) and 6.1% (2/33) of patients, respectively. Treatment-related death due to ILD occurred in one patient. Patients negative for activating EGFR mutations after osimertinib administration had longer median PFS than those positive for these mutations. Osimertinib was sufficiently effective in EGFR-TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. Plasma EGFR mutation clearance after TKI treatment could predict the response to EGFR-TKIs.
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