Patient-reported outcomes in capmatinib-treated patients with METex14-mutated advanced NSCLC: Results from the phase II GEOMETRY mono-1 study.
Authors: Wolf Juergen , Garon Edward B. , Groen Harry J.M. , Tan Daniel Shao-Weng , Gilloteau Isabelle , Le Mouhaer Sylvie , Cai Can , Chassot-Agostinho Andrea , Reynolds Maria , Odom Dawn , Heist Rebecca Suk 
Published: June 2021

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Background: Capmatinib, a potent, selective MET inhibitor, showed substantial antitumor activity and manageable tolerability in patients with METex14-mutated advanced non-small cell lung cancer (aNSCLC) in the GEOMETRY mono-1 trial (NCT02414139). Patient-reported outcomes (PROs) from this study are reported here. Methods: GEOMETRY mono-1 enrolled patients ≥18 years with METex14-mutated or MET-amplified, ALK-negative and EGFR wild-type, treatment-naïve (1L) or pre-treated (2L+) aNSCLC, to receive capmatinib orally 400 mg bid during 21-day treatment cycles. Here we report results for patients with METex14 mutations. PROs (EORTC QLQ-C30, QLQ-LC13 and EQ-5D-5L) were collected at baseline (BL) and every 6 weeks (Wks) until end of treatment. Key PROs (in patients with BL and ≥1 post-BL value) included change from BL in QLQ-C30 global health status (GHS), QLQ-LC13 symptoms (cough, chest pain and dyspnea), and EQ-5D-5L visual analogue scale (VAS), with a ≥10-point change from BL considered clinically meaningful. Time to definitive deterioration (TTDD) in QLQ-LC13 symptoms (time from treatment initiation to first date of ≥10% symptom change from BL with no later reduction) was assessed using Kaplan-Meier. QLQ-LC13 symptoms over time were explored by BIRC-assessed clinical response to capmatinib. Results: By Jan 6, 2020 cut-off, median capmatinib exposure was 48.2 (4.0 117.4) Wks and 22.1 (0.4 136.0) Wks for 1L and 2L+ patients, respectively. A total of 27/28 1L patients and 65/69 2L+ patients completed PROs at BL, and completion rate remained high (mostly > 70%) through treatment cycles. Mean [SD] BL PRO scores were moderate-to-high in 1L and 2L+ patients (GHS: 64.7 [21.6] and 58.8 [21.0.]; cough: 35.9 [32.6] and 28.7 [28.2]; chest pain: 12.8 [23.2] and 17.2 [22.7]; dyspnea: 23.5 [23.4] and 22.2 [20.8]; VAS: 67.7 [20.8] and 61.9 [18.8], respectively). Overall change from BL in PROs was maintained over time. Cough improved early, with meaningful improvements observed through cycles, notably in 1L patients (mean change from BL [SD] at Wk 7: 1L -13.0 [39.9], 2L+ -8.2 [28.4]; Wk 25: 1L -15.6 [33.0], 2L+ -6.0 [31.5]; Wk 43: 1L -28.2 [26.7], 2L+ -10.5 [27.3]). Median TTDD in GHS was 16.6 months (95% CI: 9.7, NE [not estimated]) and 12.4 months (95% CI: 4.2, 19.4) in 1L and 2L+ patients, respectively. Median TTDD for cough and chest pain was NE in both 1L and 2L+ patients, and for dyspnea was 19.4 months (95% CI: 12.4, NE) and 22.1 months (95% CI: 9.9, NE), respectively. QLQ-LC13 symptoms improved at all cycles in patients achieving clinical complete response or partial response, while symptom worsening was seen in those with no clinical response. Conclusions: Capmatinib was associated with clinically meaningful improvements in cough, delayed time to lung symptom deterioration, and preserved QoL, supporting its use as a treatment option in patients with METex14-mutated aNSCLC. Clinical trial information: NCT02414139.