Abstract 1255P
Background
The phase II VISION trial showed durable clinical activity of tepotinib in pts with advanced METex14 skipping NSCLC. To complement the clinical findings, utilities were analyzed based on pt-reported outcomes (PROs) from VISION (Cohort A; data cut: July 1, 2020). Utilities are preference-based, health-related quality of life (HRQL) metrics expressed on a scale including 0 (dead) and 1 (full health).
Methods
EORTC QLQ-C30 and EQ-5D-5L questionnaires were completed at Day 1, then every 6 weeks for 9 months, and then every 12 weeks, for up to 30 days after the last tepotinib dose. EORTC QLE-C10D and EQ-5D utilities were derived using UK value sets. Linear mixed models analyzed utilities according to baseline observation and progression status, assessed by independent review committee (IRC) or investigators (INV).
Results
Utilities were estimated for 150 of 151 pts, with 983 observations for EORTC and 907 for EQ-5D. Mean EORTC utilities increased after tepotinib initiation, from 0.657 at baseline to 0.688 in the IRC-assessed progression-free period, and decreased after progression (0.638). Consistent trends were seen when progression was based on INV assessment. Analyses of EQ-5D utilities yielded similar findings and utilities from the two questionnaires were generally highly correlated (Table). Progression status significantly predicted utility in all progression-based models (p≤0.002). In exploratory analyses based on IRC progression, EQ-5D utility was not significantly predicted by prior treatment (yes/no; p=0.580), adenocarcinoma (p=0.830) or squamous histology (p=0.930). Table: 1255P
| Mean utility* (± standard error) | |||
| EORTC | EQ-5D | ||
| Progression by independent review committee | Baseline observation | 0.657 (±0.012) | 0.640 (±0.016) |
| Pre-progression | 0.688 (±0.015) | 0.723 (±0.017) | |
| Post-progression | 0.638 (±0.012) | 0.647 (±0.015) | |
| Progression by investigator assessment | Baseline observation | 0.657 (±0.012) | 0.640 (±0.015) |
| Pre-progression | 0.685 (±0.015) | 0.719 (±0.017) | |
| Post-progression | 0.636 (±0.012) | 0.638 (±0.015) |
*On a scale including 0 (dead) and 1 (full health). EORTC, European Organisation for Research and Treatment of Cancer; EQ-5D, EuroQoL 5-dimension.
Conclusions
VISION is the first trial of a MET inhibitor to provide data on PROs and utilities in METex14 skipping NSCLC. EORTC and EQ-5D utilities show an increase in HRQL from baseline during tepotinib therapy until progression, which exceeds the previously reported minimally important difference of 0.08 for EQ-5D. Utility with tepotinib did not vary by prior treatment or histology.
Clinical trial identification
NCT02864992.
Editorial acknowledgement
Medical writing assistance (funded by Merck KGaA, Darmstadt, Germany) was provided by Mark Dyson, DPhil (Berlin, Germany) on behalf of Syneos Health (London, UK).
Legal entity responsible for the study
Merck KGaA, Darmstadt, Germany.
Funding
Merck KGaA, Darmstadt, Germany.
Disclosure
N. Reinmuth: Financial Interests, Personal, Other, Honoraria - Scientific Meetings and travelling support: BMS; Financial Interests, Personal, Other, Honoraria - Scientific Meetings and travelling support: MSD; Financial Interests, Personal, Other, Honoraria - Scientific Meetings and travelling support: AstraZeneca; Financial Interests, Personal, Other, Honoraria - Scientific Meetings and travelling support: Roche; Financial Interests, Personal, Other, Honoraria - Scientific Meetings and travelling support: Takeda; Financial Interests, Personal, Other, Honoraria - Scientific Meetings and travelling support: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria - Scientific Meetings and travelling support: Pfizer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: F. Hoffmann-La Roche; Financial Interests, Personal, Speaker’s Bureau: F. Hoffmann-La Roche; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Speaker’s Bureau: Takeda. S. Popat: Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: BeiGene; Financial Interests, Personal, Advisory Role: Blueprint; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Guardant Health; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Merck KGaA; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Takeda; Other, Personal, Other: Amgen; Other, Personal, Other: MSD; Financial Interests, Personal, Principal Investigator, Coordinating PI: ARIAD; Financial Interests, Personal, Principal Investigator, Coordinating PI: Boehringer Ingelheim; Financial Interests, Personal, Principal Investigator, Coordinating PI: Celgene; Financial Interests, Personal, Principal Investigator, Coordinating PI: Daiichi Sankyo; Financial Interests, Personal, Principal Investigator, Coordinating PI: Takeda; Financial Interests, Personal, Principal Investigator, Coordinating PI: Turning Point Therapeutics; Non-Financial Interests, Personal, Advisory Role: ALK Positive UK; Non-Financial Interests, Personal, Advisory Role: Lung Cancer Europe; Non-Financial Interests, Personal, Advisory Role: International Association for the Study of Lung Cancer and Ruth Strauss Foundation; Non-Financial Interests, Personal, Leadership Role: British Thoracic Oncology Group; Non-Financial Interests, Personal, Leadership Role: European Thoracic Oncology Platform; Non-Financial Interests, Personal, Officer: European Society of Medical Oncology; Non-Financial Interests, Personal, Member of the Board of Directors: Mesothelioma Applied Research Foundation. L. Paz-Ares: Financial Interests, Personal, Other, Consultancy: AstraZeneca; Financial Interests, Personal, Other, Consultancy: Lilly; Financial Interests, Personal, Other, Consultancy: EMD; Financial Interests, Personal, Other, Consultancy: Spectrum Pharmaceuticals; Financial Interests, Personal, Other, Consultancy: Daiichi Sankyo/Lilly; Financial Interests, Personal, Other, Research: Lilly; Financial Interests, Personal, Other, Research: Boehringer Ingelheim; Financial Interests, Personal, Leadership Role: Genomica; Financial Interests, Personal, Leadership Role: ALTUM Sequencing; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Personal, Other, Travel expenses: MSD; Financial Interests, Personal, Other, Travel expenses: BMS; Financial Interests, Personal, Other, Travel expenses: Pfizer; Financial Interests, Personal, Other, Travel expenses: Takeda; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: BMS; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: PharmaMar; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Celgene; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Personal, Other, Honoraria: Ipsen; Financial Interests, Personal, Other, Honoraria: Servier; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: Blueprint Medicines; Financial Interests, Personal, Other, Honoraria: Mirati Therapeutics; Financial Interests, Personal, Other, Honoraria: Takeda. E. Knowles: Financial Interests, Personal, Full or part-time Employment: Delta Hat. A. Hatswell: Financial Interests, Personal, Full or part-time Employment: Delta Hat. T. McLean: Financial Interests, Personal, Full or part-time Employment: Merck Serono Limited. S. Adrian: Financial Interests, Personal, Full or part-time Employment: Merck KGaA. B. Gaumond: Financial Interests, Personal, Full or part-time Employment: EMD Serono, an affiliate of Merck KGaA. H. Vioix: Financial Interests, Personal, Full or part-time Employment: Merck KGaA. P.K. Paik: Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Calithera; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Advisory Role: Xencor; Financial Interests, Personal, Advisory Role: Bicara; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Institutional, Other, research institution has received research expenses: Celgene; Financial Interests, Institutional, Other, research institution has received research expenses: EMD Serono.