Quality of Life in Adult and Pediatric Patients with Tropomyosin Receptor Kinase Fusion Cancer Receiving Larotrectinib.

Neurotrophic tyrosine receptor kinase (NTRK) gene fusions lead to chimeric tropomyosin receptor kinase (TRK) fusion proteins, which act as primary oncogenic drivers in diverse tumor types in adults and children. Larotrectinib, a highly selective and central nervous system-active TRK inhibitor, has shown high objective response rates, durable disease control, and a favorable safety profile in patients with TRK fusion cancer. The impact of larotrectinib on health-related quality of life (HRQoL) was evaluated in adult and pediatric patients in two phase I/II clinical trials (NAVIGATE; NCT02576431 and SCOUT; NCT02637687). Patients completed HRQoL questionnaires (EORTC QLQ-C30, EQ-5D-5L, and PedsQL) at baseline and at planned treatment cycle visits. Changes in questionnaire scores were evaluated over time, and by tumor type and treatment response. Questionnaires from 40 adult and 17 pediatric (2-19 years of age) patients receiving larotrectinib were completed at baseline and at least one post-baseline timepoint. Meaningful within-patient HRQoL improvements occurred at one or more timepoints in 60% of adults and 76% of pediatric patients. Sustained improvements in EORTC QLQ-C30 and PedsQL scores were rapid, occurring within 2 months of treatment initiation in 68% and 71% of patients, respectively. Improvements were observed regardless of tumor type and appeared to correlate with clinical efficacy. The rapid within-patient HRQoL improvements in adult and pediatric patients with TRK fusion cancer are consistent with the clinical profile of larotrectinib. Our results provide valuable information for use of this agent in this patient population. A plain language summary of this article is available in the supplementary appendix.

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Déclaration de conflit d'intérêts

Conflict of Interest SK discloses an advisory role, honoraria, and travel support from Bayer. JB discloses research funding from PsiOxus, Bayer, EMD Serono, Symphogen, Roche/Genentech, and Immunomed; honoraria from Nestle; and consulting/advisory roles with Rafeal, Seattle Genetics, EMD Serono, Bayer, Eisai, Taiho, Armo, Gritstone, AstraZeneca, Celgene, and Erytech. LM discloses a speaker bureau role for Bayer. CMvT discloses advisory roles for Bayer and Novartis. UNL discloses an advisory role for Bayer. RJS discloses consulting/advisory roles for Celsion, Clovis, Incyte, Flatiron Health, and Immunogen. KK and BHC are employees of Bayer HealthCare. SN was an employee of Bayer HealthCare at the time this work was conducted. CC is an employee of RTI International. TWL discloses consultancy for Novartis, Bayer, Loxo Oncology, and Lilly; and research funding from Pfizer, Novartis, Bayer, Loxo Oncology, Abbvie, Amgen, Atara, Biotherapeutics, BMS, Lilly, Epizyme, GSK, Janssen, Jubilant Pharmaceuticals, Novella Clinical, and Servier. DMH discloses consulting/advisory roles with Chugai Pharma, CytomX Therapeutics, Boehringer Ingelheim, AstraZeneca, Pfizer, Bayer, and Genentech; research funding from AstraZeneca, Puma Biotechnology, Loxo Oncology, and Bayer; and travel/accommodation/expenses from Genentech and Chugai Pharma. AD discloses honoraria/advisory roles with Ignyta/Genentech/Roche, Loxo Oncology/Bayer/Lilly, Takeda/Ariad/Millenium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, Beigene, BergenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem, and MORE Health; associated research paid to institution from Pfizer, Exelixis, GlaxoSmithKline, Teva, Taiho, and PharmaMar; research with Foundation Medicine; royalties from Wolters Kluwer; food/beverages from Merck and Puma Biotechnology; and CME honoraria from Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, and Research to Practice. DSH discloses research/grant funding from AbbVie, Adaptimmune, Amgen, AstraZeneca, Bayer, BMS, Daiichi-Sankyo, Eisai, Fate Therapeutics, Genentech, Genmab, Ignyta, Infinity, Kite, Kyowa, Lilly, Loxo Oncology, Merck, MedImmune, Mirati, MiRNA, Molecular Templates, Mologen, NCI-CTEP, Novartis, Pfizer, Seattle Genetics, and Takeda; travel/accommodation/expenses from Loxo Oncology, MiRNA, ASCO, AACR, SITC, and Genmab; consulting/advisory roles for Alpha Insights, Axiom, Adaptimmune, Baxter, Bayer, Genentech, GLG, Group H, Guidepoint Global, Infinity, Janssen, Merrimack, Medscape, Numab, Pfizer, Seattle Genetics, Takeda, and Trieza Therapeutics; and ownership interests in Molecular Match (advisor), OncoResponse (founder) and Presagia Inc (Advisor). BT and BG have nothing to disclose.