Abstract 539P
Background
NTRK1/2/3 gene fusions are oncogenic drivers found in a range of tumour types. Entrectinib is a potent TRKA/B/C inhibitor that had a favourable efficacy and safety profile in STARTRK-2 pts with NTRK-fp tumours. We present the impact of entrectinib on PROs including health-related quality of life (HRQoL).
Methods
STARTRK-2 is an open-label, multicentre, phase II basket study. PROs were pre-specified secondary endpoints evaluated in all enrolled pts with NTRK-fp tumours. All pts completed the European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaire (QLQ-C30). NSCLC and CRC pts completed the QLQ-LC13 and the QLQ-CR29 modules, respectively. A clinically meaningful change from baseline is >10 points. PROs were completed on D1, C1 and then at each 4-wk treatment cycle.
Results
This analysis included 71 NTRK-fp efficacy-evaluable pts (data cut-off 31 Oct 2018) with follow-up ≥6 months. Questionnaire completion rates were ≥85.7% at baseline and ≥60% at study visits where ≥25% of pts were still enrolled. Pts reported moderate/high baseline functioning and HRQoL scores. While on entrectinib, scores generally showed no change or a trend towards an improvement from baseline up to 12.3 points (Table); role functioning and pain showed clinically meaningful improvement. Pts reported moderate lung cancer-related symptom burden at baseline, with trends towards improvement in symptom severity during treatment, including a clinically meaningful improvement in cough. CRC-related symptoms (e.g. bloating) were unchanged or improved over time. Symptoms commonly associated with treatment (e.g. nausea) were absent or of low severity.
Conclusions
These PRO data support a positive benefit-risk profile for entrectinib. Treatment burden was minimal, and pts with NTRK-fp tumours who were symptomatic at baseline demonstrated trends towards improvement in HRQoL and cancer-related symptoms during treatment. Table: 539P
| NTRK-fp tumours (n=71) | ||
| Mean baseline score | Change in mean score from baseline, Cycle 13 Day 1* | |
| Higher score = better HRQoL and function (improvement) | ||
| EORTC QLQ-C30: Functional scales (n=71) | ||
| Global health status | 68.59 | +5.26 |
| Functioning | ||
| Physical | 74.77 | +6.32 |
| Role | 66.92 | +12.28 |
| Cognitive | 83.85 | 0.00 |
| Lower score = lower symptom severity (improvement) | ||
| EORTC QLQ-C30: Symptom scales (n=71) | ||
| Fatigue | 34.87 | –9.94 |
| Dyspnoea | 21.54 | –8.77 |
| Pain | 25.38 | –12.28 |
| EORTC QLQ-LC13: Symptom scales (n=12) | ||
| Cough | 38.89 | –11.11 |
| Chest pain | 5.56 | 0.00 |
| Dyspnoea | 26.85 | –7.41 |
Clinically meaningful change from baseline is >10 points. ∗Last time point at which ≥25% of pts remained enrolled on the study.
Clinical trial identification
STARTRK-2 (NCT02568267).
Editorial acknowledgement
Third-party medical writing assistance, under the direction of the authors, was provided by Laura Vergoz, PhD, of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
A.P. Conley: Advisory/Consultancy, Research grant/Funding (self): Genentech/Roche. G.D. Demetri: Honoraria (self): M.J. Hennessey / OncLive, Medscape, AACR/ASCO; Advisory/Consultancy: Roche, Ignyta, Genentech, Bayer, EMD-Serono, Loxo Oncology, Daiichi Sankyo, WCG/Arsenal Capital, Blueprint Medicines, Merrimack Pharmaceuticals, PharmaMar, Pfizer, Novartis, Epizyme, AbbVie, GlaxoSmithKline, Janssen, Mirati, Sanofi, ICON PLC, Ziopharm; Research grant/Funding (institution): Roche, Ignyta, Bayer, Loxo Oncology, Daiichi-Sankyo, Janssen, Pfizer, Novartis, Epizyme, AbbVie; Travel/Accommodation/Expenses: Epizyme, Roche; Shareholder/Stockholder/Stock options: Blueprint Medicines, G1 Therapeutics, CARIS Life Sciences, Bessor Pharmaceuticals, ERASCA Pharmaceuticals, CHAMPIONS Oncology, Translate BIO, RELAY Therapeutics, Caprion HistoGeneX; Licensing/Royalties: Novartis to Dana-Farber Cancer Institute; Officer/Board of Directors, Board of Directors Member: Blueprint Medicines, Translate BIO; Non-remunerated activity/ies: Alexandria Real Estate Equities; Advisory/Consultancy: Polaris Pharmaceuticals, Medscape, Relay Therapeutics, Caprion/HistoGeneX, McCann Health. R.C. Doebele: Advisory/Consultancy: Ignyta, Genentech/Roche, Loxo Oncology, Bayer, Eli Lilly, AstraZeneca, Pfizer, Blueprint Medicines, Anchiano, and Rain Therapeutics; Research grant/Funding (institution): Ignyta, Loxo, Mirati, Pfizer, Eli Lilly, and Strategia; Travel/Accommodation/Expenses: Ignyta, Genentech/Roche, Eli Lilly, Pfizer, Blueprint Medicines, and Rain Therapeutics; Shareholder/Stockholder/Stock options: Rain Therapeutics; Licensing/Royalties, Patent and biologic material licensing fees: Ignyta, Loxo, Abbott Molecular, Genentech/Roche, Chugai, Foundation Medicine, Black Diamond, Rain Therapeutics, Voronoi, Pearl River, Ariad. A. Drilon: Honoraria (institution): Ignyta/Roche/Genentech, Loxo/Bayer/Lily, TP Therapeutics, AstraZeneca, Pfizer, Blueprint, Takeda/Ariad/Millennium, Helsinn, BeiGene, BerGenBio, Hengrui, Exelixis, Tyra, Verastem, MORE Health, AbbVie, 14ner/Elevation Oncology, Axis, Peerview Institute; Research grant/Funding (self): Foundation Medicine; Research grant/Funding (institution): Pfizer, Exelixis, Taiho, Teva, GlaxoSmithKline, Pharmamar; Licensing/Royalties: Wolters Kluwer; Honoraria (institution): OncLive, Paradigm Medical Communications, Remedica Ltd, ArcherDX, Foundation Medicine, PeerVoice, Research to Practice, Medscapem, WebMD. L. Paz-Ares: Advisory/Consultancy: Genentech/Roche, Loxo Oncology, Bayer, Eli Lilly, AstraZeneca, Pfizer, Bayer, Merck Sharp & Dohme, Novartis, Amgen, Pharmamar, Boehringer Ingelheim, Celgene, Servier, Sysmex, Incyte, Ipsen, Adacap, Sanofi, and Blueprint Medicines; Research grant/Funding (institution): BMS, AstraZeneca, and Merck Sharp & Dohme; Shareholder/Stockholder/Stock options: Altum sequencing; Officer/Board of Directors: Genómica, Altum sequencing. P. Cassier: Honoraria (self): Novartis, Roche/Genentech, Blueprint Medicines, Amgen, AstraZenca, Merck Serono; Honoraria (institution): Celgene, Plexxikon, AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Taiho Pharmaceutical, Toray Industries, Transgene, Loxo, GlaxoSmithKline, Innate Pharma, Janssen; Travel/Accommodation/Expenses: Roche, Amgen, Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme, Netris Pharma. S. Siena: Advisory/Consultancy: Amgen, Bayer, BMS, CheckMab, Celgene, Daiichi Sankyo, Incyte, Merck, Novartis, Roche, and Seattle Genetics. M-J. Ahn: Honoraria (self): AstraZeneca, Lilly, Takeda, Roche, MSD; Advisory/Consultancy: AstraZeneca, Lilly, Takeda, Roche, MSD, Merck, Boehringer Ingelheim, Ono Pharmaceutical, Bristol-Myers Squibb, and Alpha Pharmaceutical, Progeneer. T. Seto: Honoraria (self): Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, MSD, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, Takeda Pharmaceutical; Research grant/Funding (institution): AbbVie, AstraZeneca, Bayer Yakuhin, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, LOXO Oncology, Merck Serono, MSD, Nippon Boehringer Ingelheim, Novartis Pharma, Pfizer Japan, Takeda Pharmaceutical; Full/Part-time employment: Precision Medicine Asia; Honoraria (self): Thermo Fisher Scientific. S-H.I. Ou: Honoraria (self): Pfizer, Roche/Genentech, AstraZenca, Takeda/ARIAD, Daiichi Sankyo; Honoraria (institution): Pfizer, Roche/Genentech, AstraZenca, Takeda/ARIAD, Daiichi Sankyo; Advisory/Consultancy: Pfizer, Roche/Genentech, AstraZenca, Takeda/ARIAD, Daiichi Sankyo; Speaker Bureau/Expert testimony: Pfizer, Roche/Genentech, AstraZenca, Takeda/ARIAD, Daiichi Sankyo; Research grant/Funding (institution): Pfizer, Roche/Genentech, AstraZenca, Takeda/ARIAD, Daiichi Sankyo, Janssen, Mirati, Revolution Medicine, Lilly/LOXO Oncology, BluePrint Medicine; Shareholder/Stockholder/Stock options: Turning Point Therapeutics. C. Grohé: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Lilly, Novartis; Research grant/Funding (self), Research grant/Funding (institution): Novartis, Ipsen. V. Zagonel: Honoraria (institution): Bayer, Roche, Lilly; Advisory/Consultancy: BMS, Merck; Speaker Bureau/Expert testimony: Bayer, Roche, BMS, Astellas, Servier, AstraZenca, Lilly; Research grant/Funding (institution): Roche, Bayer, BMS, Jansen , Lilly; Travel/Accommodation/Expenses: Bayer, Roche, Servier. A. Spira: Honoraria (institution): Amgen, Novartis, BMS, Merck, Takeda, Janssen, AstraZenca; Advisory/Consultancy: Amgen, Novartis; Research grant/Funding (institution): Roche, Amgen, Takeda, Janssen, Cytomx, AbbVie, AstraZenca. A. Cheng: Research grant/Funding (institution): Roche. A. Kapre: Full/Part-time employment: Genentech. E. Piault: Full/Part-time employment: Genentech, AstraZeneca. C.D. Rolfo: Advisory/Consultancy: Mylan, Oncompass, Archer, Inivata, MD Serono; Speaker Bureau/Expert testimony: Merck Sharp and Dohme, AstraZeneca; Leadership role: IASLC Educational Committee Member and LATAM (IASLC) co-chair, ESO Scientific Committee Board, ISLB Vice-president and Educational Chair, Educational Chair OLA ; Research grant/Funding (self): Biomarkers, Guardant Health (Research collaboration) Lung Cancer Research Foundation-Pfizer Grant; Research grant/Funding (institution): American Cancer Society grant PY30 NIH grant. All other authors have declared no conflicts of interest.