OBJECTIVES In non-small cell lung cancer patients with acquired resistance to first- or second-generation EGFR-TKIs, osimertinib is approved in the presence of the T790 M resistance mutation. We assessed the efficacy of osimertinib in both T790M-positive and T790M-negative patients. MATERIALS AND METHODS The TREM-study is an investigator-initiated, multi-centre, single-arm, phase 2 clinical trial conducted in five Northern European countries. Patients with progression on at least one previous EGFR-TKI were assigned to treatment with 80 mg of osimertinib daily until radiological progression or death. Patients were included regardless of the presence of T790 M. The primary endpoint was objective response rate (ORR). RESULTS Of 199 included patients, 120 (60 %) were T790M-positive, 52 (26 %) were T790M-negative and 27 (14 %) had unknown T790M-status. 24 % had brain metastases and 15 % had an ECOG performance status of 2. Overall ORR was 48 % (95 % CI, 41 %-55 %), 60 % (51 %-69 %) for T790M-positive patients and 28 % (15 %-41 %) for T790M-negative patients, p < 0.001. ORR for patients with co-occurring del19 vs L858R was 61 % vs 32 %, p = 0.001. Duration of response was similar between the T790M-positive and -negative groups (11.8 vs 10.7 months, p = 0.229). Overall median progression-free survival (PFS) was 8.9 months (95 % CI, 7.4-10.5), and 10.8 vs 5.1 months for T790M-positive vs -negative patients (HR 0.62, p = 0.007). Median overall survival (OS) was 17.9 months (95 % CI, 14.4-21.3). For T790M-positive vs -negative median OS was 22.5 vs 13.4 months, (HR 0.55, p = 0.002). CONCLUSIONS This study confirms the efficacy of osimertinib for T790M-positive patients. There was also clinically significant activity of osimertinib in a proportion of T790M-negative patients. CLINICAL TRIAL REGISTRATION This trial is registered with ClinicalTrials.gov (NCT02504346).

中文翻译：

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奥西替尼用于EGFR突变的晚期非小细胞肺癌的T790M阳性和阴性患者（TREM研究）。

目的在对第一代或第二代EGFR-TKI具有获得性耐药性的非小细胞肺癌患者中，在存在T790 M耐药性突变的情况下，批准使用osimertinib。我们评估了Oimertinib在T790M阳性和T790M阴性患者中的疗效。材料和方法TREM研究是由研究人员发起的，在五个北欧国家进行的多中心，单臂2期临床试验。在至少一项先前的EGFR-TKI上进展的患者，每天接受80 mg奥西替尼治疗，直至放射学进展或死亡。无论是否存在T790 M，均纳入患者。主要终点为客观缓解率（ORR）。结果在199名患者中，有120名（60％）为T790M阳性，T790M阴性的为52（26％），T790M状态未知的为27（14％）。T790M阳性患者的脑转移率为24％，ECOG表现状态为2。15％的总ORR为48％（95％CI，41％-55％），60％（51％-69％）。 T790M阴性患者（15％-41％），p <0.001。del19 vs L858R并发患者的ORR为61％vs 32％，p = 0.001。T790M阳性和阴性组的反应持续时间相似（11.8 vs 10.7个月，p = 0.229）。T790M阳性与阴性患者的总体中位无进展生存期（PFS）为8.9个月（95％CI，7.4-10.5），分别为10.8和5.1个月（HR 0.62，p = 0.007）。中位总生存期（OS）为17.9个月（95％CI，14.4-21.3）。对于T790M阳性与阴性，中位OS​​为22.5 vs 13.4个月（HR 0.55，p = 0.002）。结论这项研究证实了奥西替尼对T790M阳性患者的疗效。在一部分T790M阴性患者中，奥西替尼在临床上也具有明显的活性。临床试验注册本试验已在ClinicalTrials.gov（NCT02504346）中注册。