Abstract 361P
Background
HER2 amplification/overexpression (HER2-positive [HER2+]) is reported in ∼3-5% of all pts with mCRC. Treatment strategies for mCRC focus on prolonging survival, delaying tumor progression, and maintaining health-related quality of life (HRQoL). Tucatinib (TUC) is a highly selective, HER2-directed, tyrosine kinase inhibitor. Results from the MOUNTAINEER (NCT03043313) study demonstrated that dual HER2 inhibition with TUC and trastuzumab (T) in pts with HER2+ RAS WT mCRC is well tolerated with durable clinical benefit. Here we report the impact of TUC + T on HRQoL in pts from MOUNTAINEER.
Methods
MOUNTAINEER is a global, multi-center, open-label, phase 2 trial that enrolled pts with HER2+ RAS WT mCRC previously treated with fluoropyrimidine, oxaliplatin, irinotecan, and anti-VEGF mAb. Overall, 117 pts were enrolled or randomized to receive TUC + T (cohorts A [n=45] and B [n=41]) or TUC monotherapy (cohort C [n=31]). HRQoL was assessed with EQ-5D-5L and EORTC QLQ-C30 for cohorts B and C. Cohort A was not assessed for HRQoL. Questionnaires were administered at predose on Cycle 1 Day 1 (C1 D1), C1 D8, C1 D15, then every D1 of C2-4 and every 3 following cycles until end of treatment. HRQoL data for cohorts B and C were analyzed using descriptive statistics.
Results
Thirty-seven pts in cohort B and 28 pts in cohort C had ≥1 dose of study treatment and completed baseline and at least 1 follow-up HRQoL assessment. For both cohorts, the mean changes from baseline during the treatment period for EORTC QLQ-C30 generally remained stable across all scales, including global health status/QoL and functional domains. Descriptive analyses showed some fluctuations in observed individual domain scores; however, global health status/QoL remained stable over time. EQ-5D-5L VAS scores also remained similar over time.
Conclusions
HRQoL was maintained for pts treated with TUC + T or TUC monotherapy throughout the treatment period. These results, together with the primary efficacy and safety data from MOUNTAINEER, further support the overall tolerability profile of TUC + T and suggest this regimen may be an important treatment option for pts with HER2+ mCRC.
Clinical trial identification
NCT03043313.
Editorial acknowledgement
Under guidance of the authors, assistance in medical writing was provided by Irene Park, PhD, of Seagen Inc. and was funded by Seagen Inc. in accordance with Good Publication Practice (GPP3) guidelines.
Legal entity responsible for the study
Seagen Inc.
Funding
This study was sponsored by Seagen Inc., Bothell WA, USA.
Disclosure
C. Wu: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Array Biopharma, Pfizer; Financial Interests, Personal, Invited Speaker: PrecisCA; Financial Interests, Institutional, Invited Speaker, PI for investigator initiated clinical trial: Vaccinex; Financial Interests, Institutional, Invited Speaker, local PI for phase III clinical trial: Boston Biomedical Inc; Financial Interests, Institutional, Invited Speaker: Lycera, Seagen, Symphogen, Rapt Therapeutics, INBRX; Non-Financial Interests, Advisory Role, Safety monitoring committee: Seagen. J.H. Strickler: Financial Interests, Personal, Advisory Board: SeaGen, AstraZeneca, Amgen, Pfizer, Bayer, AbbVie, Natera, Viatris, Inivata, Silverback Therapeutics; Financial Interests, Personal, Other, Consulting: Mereo, GSK, Pionyr Immunotherapeutics; Financial Interests, Institutional, Invited Speaker: SeaGen, Roche Genentech, AbbVie, AstraZeneca, Amgen, AStar D3, Sanofi, Curegenix, Nektar, Leap Therapeutics, Daiichi Sankyo, Erasca, Gossamer Bio, Silverback Therapeutics. A. Cercek: Financial Interests, Personal, Other, Consulting: Array Biopharma, Bayer, Proteus; Financial Interests, Institutional, Research Grant: AbbVie, Rgenix, Seagen Inc., Tesaro. S. Siena: Financial Interests, Personal, Other, Consulting: Amgen, Bayer, Bristol-Myers Squibb, CheckmAb, Clovis Oncology, Daiichi Sankyo, Incyte, Merck, Novartis, Seagen Inc., Roche/Genentech; Financial Interests, Personal, Ownership Interest, Equity ownership: Guardant, Myriad; Financial Interests, Personal, Royalties: Amgen; Financial Interests, Institutional, Research Grant: MSD Oncology; Financial Interests, Personal, Other, Travel expenses: Amgen, Bayer, Roche. T. André: Financial Interests, Personal, Advisory Board, Advisory Board on February 12, 2021: Astellas pharma; Financial Interests, Personal, Advisory Board, Advisory Board on February 2021: Kaleido Biosciences; Financial Interests, Personal, Invited Speaker, and advisory board: Amgen; Financial Interests, Personal, Invited Speaker, Invited speaker in a symposium December 2020: AstraZeneca; Financial Interests, Personal, Advisory Board, and consultant fees and consultant contract: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board, Advisory board in January 2020: Clovis; Financial Interests, Personal, Advisory Board, Advisory board in January 2020: Gritstone Oncology; Financial Interests, Personal, Advisory Board: Haliodx; Financial Interests, Personal, Advisory Board, and consultant fees/consultant contract and invited speaker: MSD Oncology; Financial Interests, Personal, Invited Speaker, and other: Pierre Fabre; Financial Interests, Personal, Invited Speaker, in an symposium in 2020: Roche; Financial Interests, Personal, Invited Speaker, in a meeting in 2019: Ventana; Financial Interests, Personal, Invited Speaker, In an educational meeting in 2019: Sanofi; Financial Interests, Personal, Advisory Board, in a symposium in 2020: Servier; Financial Interests, Personal, Expert Testimony, Consultant with personal fees and invited speaker: Servier; Financial Interests, Personal, Advisory Board, in 2019: GSK; Financial Interests, Personal, Invited Speaker, in 2020 and 2021: GSK; Financial Interests, Personal, Expert Testimony, consultant contract: Seagen; Financial Interests, Personal, Invited Speaker, Virtual symposuim Lecture: 1 MSI-H CRC: Implementation of Immunotherapy in clinical practice (30 minutes) – (this will be pre-recorded) Q&A – Live Q&A – (10 minutes) (on July 2, 2021): MSD Oncology; Financial Interests, Personal, Invited Speaker, June 2022: Sanofi; Financial Interests, Personal, Expert Testimony, Contract: Merck & Co., Inc, Gritstone Oncologie; Financial Interests, Personal, Advisory Board, Contrat: BMS; Financial Interests, Institutional, Other, Investigator and Scientific Committee president: Gercor Academic group; Financial Interests, Institutional, Invited Speaker, PI Garnet study: GSK; Financial Interests, Institutional, Invited Speaker, Keynote 164 and 171 and 811: MSD; Financial Interests, Institutional, Invited Speaker, BMS CA209-8HW, BMS CA209-142, BMS CA209-577: BMS; Financial Interests, Institutional, Invited Speaker, SPOTLIGHT study: Astellas; Financial Interests, Personal, Invited Speaker, and international PI: Servier; Non-Financial Interests, Invited Speaker, Vice President: Gercor group; Non-Financial Interests, Invited Speaker, Member of Scientific Committee: ARCADFoundation. K. Ng: Financial Interests, Personal, Other, Consulting: Bayer, Genentech/Roche, Lilly, Seagen Inc., Tarrex Biopharma, X-Biotix Therapeutics; Financial Interests, Institutional, Research Grant: Celgene, Genentech/Roche, Gilead, Pharmavite, Revolution Medicines, Trovagene. E. Van Cutsem: Financial Interests, Personal, Advisory Board: AbbVie, Astellas, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Halozyme, GSK, Helsinn, Incyte, Ipsen, Janssen Research, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Pierre Fabre, Roche, Seagen Inc., Servier, Sirtex, Terumo, Taiho, TRIGR, Zymeworks; Financial Interests, Institutional, Research Grant: Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Seagen Inc., Servier. A.S. Paulson: Financial Interests, Personal, Invited Speaker, Medical education, non-branded, industry sponsored: Ideo Oncology; Financial Interests, Personal, Advisory Board: Amgen, BMS, Eisai, Ipsen, Incyte, Exelixis, AAA, Pfizer, QED, Lilly, Mirati, Hutchinson, Astellas; Financial Interests, Personal, Stocks/Shares: Alexion, Actinium, Aptose; Financial Interests, Invited Speaker: Ipsen, Hutchinson, BMS, Exelixis, hutchinson med, Taiho, Lilly, AstraZeneca, Incyte, Seattle Genetics, Deciphera, Tempus, Zentalis, G1 therapeutics, Merck, Camurus, Novartis, Surface, Relay Therapeutics; Financial Interests, Institutional, Invited Speaker: Mirati, Bayer. J. Hubbard: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Advisory Board: Incyte, Bayer, BeiGene; Financial Interests, Institutional, Invited Speaker: Boston Biomedical, Senhwa Biosciences, Bayer, Merck, Taiho Pharmaceutical, TreoBio, Hutchison MediPharma, Seattle Genetics, Tovogene, TriOncology, Incyte, Pionyr, G1 Therapeutics, eFFECTOR Therapeutics, Roche. A. Coveler: Financial Interests, Institutional, Invited Speaker: Seagen, AbGenomics, Novocure, Amgen, Actuate Therapeutics, Surface Oncology, Nucana, Nextrast. C. Fountzilas: Financial Interests, Institutional, Research Grant: Pfizer Inc, Taiho Oncology, Merck Sharp & Dohme Corp., National Comprehensive Cancer Network; Financial Interests, Institutional, Invited Speaker: Seattle Genetics, Inc., TransThera Biosciences, AstraZeneca, Aravive, Inc., Merck Sharp & Dohme Corp., Puma Biotechnology, Kadmon, Astellas Pharma, Pfizer Inc, Dragonfly Therapeutics, MedImmune, LLC., Hoosier Cancer Research Network, Incyte Corporation, Rafael Pharmaceuticals, Kinex Phamaceuticals, Syndax Pharmaceuticals, SWOG, National Cancer Institute, Erythech Pharma, Lilly, Corcept Therapeutics, Ipsen. A. Kardosh: Financial Interests, Personal, Advisory Board: Exelixus; Financial Interests, Personal, Full or part-time Employment: OHSU. P.M. Kasi: Financial Interests, Personal, Advisory Board, Consultancy/Advisory Board: Foundation Medicine, Natera Oncology, AstraZeneca, Merck MSD, Tempus, Bayer, Lilly, Delicath Systems, QED Therapeutics, Servier, Taiho Oncology, Exact Sciences, Eisai; Financial Interests, Institutional, Advisory Board, Consultancy/Advisory Board: Taiho, Ipsen; Financial Interests, Institutional, Funding, Investigator initiated trial cooperative group PI trial support and funding.: Tersera; Financial Interests, Institutional, Funding, Investigator initiated trial support and funding: Boston Scientific. H.J. Lenz: Financial Interests, Personal, Advisory Board, Advisory Role and Lectures: Bayer; Financial Interests, Personal, Advisory Board, Advisory Role and Lectures: Merck; Financial Interests, Personal, Advisory Board, Advisory Role and lecture: ROche; Financial Interests, Personal, Advisory Board: Jazz Pharmaceuticals, oncocyte, Orion, Astellas, BMS; Financial Interests, Personal, Advisory Board, Scientific Advisory Board: 3T Biosscience; Financial Interests, Personal, Advisory Board, Advisory Board: Fulgent. K.K. Ciombor: Financial Interests, Personal, Advisory Board: Pfizer, Merck, Lilly/Loxo, Replimune, Personalis; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Institutional, Invited Speaker: Genentech, Merck, Incyte, Seagen, BMS, Nucana, Daiichi Sankyo, Calithera, Array. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Hoffman La - Roche, Bristol Myers Squibb, Servier, Amgen, Merck Serono, Array Biopharma, Sanofi, Bayer; Financial Interests, Institutional, Research Grant: Hoffman La-Roche, Sanofi Aventis, Amgen, Merck Serono, MSD, Boehringer Ingelheim, AbbVie, Pierre-Fabre, Novartis, Bristol-Myers Squibb, GlaxoSmithKline, Medimmune, Array Pharmaceuticals, AstraZeneca. L. Hsu: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc. M. Stecher: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc. K. Zhao: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc. T. 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