Department of Internal Medicine, Center for Integrated Oncology, University Hospital Cologne, Cologne, Germany.
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Eur J Cancer. 2023 Apr;183:98-108. doi: 10.1016/j.ejca.2022.10.030. Epub 2022 Dec 10.
Capmatinib, a MET inhibitor, showed substantial antitumour activity with manageable side effects in patients with MET exon 14 (METex14)-mutated advanced non-small cell lung cancer (aNSCLC) in the GEOMETRY mono-1 study. We report patient-reported outcomes (PROs) from this study.
Enrolled treatment-naïve (1L) or pre-treated (2L) patients with aNSCLC with a METex14-skipping mutation received 400 mg capmatinib twice daily during 21-day treatment cycles. PROs were collected at baseline and every six weeks thereafter using EORTC QLQ-C30 global health status/quality of life (GHS/QoL), QLQ-LC13 symptoms, and EQ-5D-5L visual analogue scale (VAS) questionnaires.
As of 6 January 2020, 27/28 1L and 65/69 2L patients had completed PROs at baseline; compliance rates remained >70%. Cough improved early, with meaningful improvements (≥10-point change from baseline) observed throughout cycles (mean change from baseline [SD] by week 7: 1L -13.0 [39.9], 2L -8.2 [28.4]; week 43: 1L -28.2 [26.7], 2L -10.5 [27.3]). QoL, assessed by GHS/QoL and VAS, improved by week 7 in 1L and 2L patients, with improvements generally sustained over time. Median time to definitive deterioration (TTDD) in GHS/QoL was 16.6 months (95% CI: 9.7, not estimable [NE]) in 1L and 12.4 months (95% CI: 4.2, 19.4) in 2L patients. Median TTDD for dyspnoea was 19.4 months (95% CI: 12.4, NE) and 22.1 months (95% CI: 9.9, NE) for 1L and 2L patients, respectively, and NE for cough and chest pain.
Capmatinib was associated with clinically meaningful improvements in cough and preserved QoL, further supporting its use in patients with METex14-mutated aNSCLC.
ClinicalTrials.gov registry number: NCT02414139.
在 GEOMETRY mono-1 研究中，MET 抑制剂卡马替尼（capmatinib）在 MET 外显子 14（METex14）突变的晚期非小细胞肺癌（aNSCLC）患者中显示出显著的抗肿瘤活性，且副作用可管理。我们报告了这项研究的患者报告结局（PRO）。
纳入未经治疗（1L）或经治（2L）的具有 METex14 跳跃突变的 aNSCLC 患者，接受每日两次 400mg 卡马替尼治疗，治疗周期为 21 天。在基线和此后每六周使用 EORTC QLQ-C30 全球健康状况/生活质量（GHS/QoL）、QLQ-LC13 症状和 EQ-5D-5L 视觉模拟量表（VAS）问卷收集 PRO。
截至 2020 年 1 月 6 日，28 例 1L 和 69 例 2L 患者完成了基线 PRO；合规率保持在>70%。咳嗽早期改善，整个周期内均观察到有意义的改善（较基线改善≥10 分）（第 7 周时的平均变化[SD]：1L-13.0[39.9]，2L-8.2[28.4]；第 43 周：1L-28.2[26.7]，2L-10.5[27.3]）。1L 和 2L 患者的 GHS/QoL 和 VAS 评估的 QoL 在第 7 周得到改善，并且随着时间的推移，改善通常持续。1L 患者的 GHS/QoL 中明确恶化的中位时间（TTDD）为 16.6 个月（95%CI：9.7，无法估计[NE]），2L 患者为 12.4 个月（95%CI：4.2，19.4）。1L 和 2L 患者的呼吸困难 TTDD 中位数分别为 19.4 个月（95%CI：12.4，NE）和 22.1 个月（95%CI：9.9，NE），咳嗽和胸痛的 TTDD 为 NE。
卡马替尼与咳嗽的临床显著改善和保留的 QoL 相关，进一步支持其在 METex14 突变的 aNSCLC 患者中的应用。
ClinicalTrials.gov 注册号：NCT02414139。
