Highlights
- •Capmatinib is indicated for advanced NSCLC with MET exon 14 skipping alterations.
- •We present the analysis of the patient-reported outcomes from the GEOMETRY mono-1 trial.
- •Patient-reported outcomes included the EORTC QLQ-C30, EORTC QLQ-LC13, and EQ-5D-5L.
- •Capmatinib led to clinically meaningful improvements in cough and preserved QoL.
- •Benefit was observed for both treatment-naïve and previously treated patients.
Abstract
Introduction
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.
Methods
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.
Results
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.
Conclusions
Capmatinib was associated with clinically meaningful improvements in cough and preserved
QoL, further supporting its use in patients with METex14-mutated aNSCLC.
Trial registration
ClinicalTrials.gov registry number: NCT02414139.
Keywords
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References
- Module 1 Working Group. Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK: a population-based study, 2004–2007.Thorax. 2013; 68: 551-564https://doi.org/10.1136/thoraxjnl-2012-202297
- Changing trends in diagnosis, staging, treatment and survival in lung cancer: comparison of three consecutive cohorts in an Australian lung cancer centre.Intern Med J. 2016; 46: 946-954https://doi.org/10.1111/imj.13132
- Symptom burden and performance status in a population-based cohort of ambulatory cancer patients.Cancer. 2010; 116: 5767-5776https://doi.org/10.1002/cncr.25681
- Evolution of symptom burden of advanced lung cancer over a decade.Clin Lung Cancer. 2017; 18 (e6): 274-280https://doi.org/10.1016/j.cllc.2016.12.010
- Newly diagnosed patients with advanced non-small cell lung cancer: a clinical description of those with moderate to severe depressive symptoms.Lung Cancer. 2019; 145: 195-204https://doi.org/10.1016/j.lungcan.2019.11.015
- Symptoms in adults with lung cancer. A systematic research review.J Pain Symptom Manag. 2000; 19: 137-153https://doi.org/10.1016/s0885-3924(99)00150-5
- Distress screening in a multidisciplinary lung cancer clinic: prevalence and predictors of clinically significant distress.Lung Cancer. 2007; 55: 215-224https://doi.org/10.1016/j.lungcan.2006.10.001
- Comprehensive molecular profiling of lung adenocarcinoma.Nature. 2014; 511: 543-550https://doi.org/10.1038/nature13385
- Activation of MET by gene amplification or by splice mutations deleting the juxtamembrane domain in primary resected lung cancers.J Thorac Oncol. 2009; 4: 5-11https://doi.org/10.1097/JTO.0b013e3181913e0e
- MET amplification and exon 14 splice site mutation define unique molecular subgroups of non-small cell lung carcinoma with poor prognosis.Clin Cancer Res. 2016; 22: 3048-3056https://doi.org/10.1158/1078-0432.CCR-15-2061
- Profiling of oncogenic driver events in lung adenocarcinoma revealed MET mutation as independent prognostic factor.J Thorac Oncol. 2015; 10: 1292-1300https://doi.org/10.1097/JTO.0000000000000620
- Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors.Cancer Discov. 2015; 5: 850-859https://doi.org/10.1158/2159-8290.CD-15-0285
- Impact of MET inhibitors on survival among patients with non-small cell lung cancer harboring MET exon 14 mutations: a retrospective analysis.Lung Cancer. 2019; 133: 96-102https://doi.org/10.1016/j.lungcan.2019.05.011
- Capmatinib US prescribing information.Novartis, New Jersey, USA2020
- Tepotinib US prescribing information.Merck KGaA, Rockland, USA2021
Novartis. Novartis announces MET inhibitor Tabrecta™ approved in Japan for advanced non-small cell lung cancer with METex14 | Novartis. https://www.novartis.com/news/media-releases/novartis-announces-met-inhibitor-tabrecta-approved-japan-advanced-non-small-cell-lung-cancer-metex14. Accessed April 1, 2022.
Novartis. Novartis announces Tabrecta first published overall survival and updated overall response data in patients with METex14 metastatic NSCLC. https://www.novartis.com/news/media-releases/novartis-announces-tabrecta-first-published-overall-survival-and-updated-overall-response-data-patients-metex14-metastatic-nsclc. Accessed April 1, 2022.
- GEOMETRY mono-1 investigators. Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer.N Engl J Med. 2020; 383: 944-957https://doi.org/10.1056/NEJMoa2002787
- Safety of MET tyrosine kinase inhibitors in patients with MET exon 14 skipping non-small cell lung cancer: a clinical review.Clin Lung Cancer. 2022; 23: 195-207https://doi.org/10.1016/j.cllc.2022.01.003
- The European organization for research and treatment of cancer qlq-C30: a quality-of-life instrument for use in international clinical trials in Oncology.J Natl Cancer Inst. 1993; 85: 365-376https://doi.org/10.1093/jnci/85.5.365
- The EORTC QLQ-LC13: a modular supplement to the EORTC core quality of life questionnaire (QLQ-C30) for use in lung cancer clinical trials. EORTC study group on quality of life.Eur J Cancer. 1994; 30A: 635-642https://doi.org/10.1016/0959-8049(94)90535-5
- Interpreting the significance of changes in health-related quality-of-life scores.J Clin Oncol. 1998; 16: 139-144https://doi.org/10.1200/JCO.1998.16.1.139
- Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L).Qual Life Res. 2011; 20: 1727-1736https://doi.org/10.1007/s11136-011-9903-x
- Quality of life of patients with lung cancer.OncoTargets Ther. 2016; 9: 1023-1028https://doi.org/10.2147/OTT.S100685
- Estimation of minimally important differences in EQ-5D utility and VAS scores in cancer.Health Qual Life Outcome. 2007; 5: 70https://doi.org/10.1186/1477-7525-5-70
- Health-related quality of life in patients with NSCLC harboring MET exon 14 skipping treated with tepotinib.in: Presented at the European Society for Medical Oncology Virtual Congress. 2020 (September 19–21)
- Evidence-based guidelines for interpreting change scores for the European organisation for the research and treatment of cancer quality of life questionnaire core 30.Eur J Cancer. 2012; 48: 1713-1721https://doi.org/10.1016/j.ejca.2012.02.059
- Evidence-based guidelines for determination of sample size and interpretation of the European organisation for the research and treatment of cancer quality of life questionnaire core 30.J Clin Oncol. 2011; 29: 89-96https://doi.org/10.1200/JCO.2010.28.0107
Article info
Publication history
Published online: January 10, 2023
Accepted:
October 28,
2022
Received in revised form:
October 26,
2022
Received:
May 23,
2022
Identification
Copyright
© 2022 Published by Elsevier Ltd.
