DESTINY-Breast04 (NCT03734029) demonstrated significantly improved overall and progression-free survival (PFS) with T-DXd vs TPC in pts with HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization-negative) mBC, with manageable safety. Here, we report additional safety data.
Pts with centrally confirmed HER2-low mBC, treated with 1-2 prior lines of chemotherapy, were randomly assigned 2:1 to receive T-DXd or TPC. An analysis of selected treatment-emergent adverse events (TEAEs) and age (<65 vs ≥65 years [y]) was done; endpoints included time to first onset (TTO), duration of first event (DUR), and resolution.
At data cutoff (January 11, 2022), median (m) treatment duration was 8.2 months (mo; range [r], 0.2-33.3) for T-DXd vs 3.5 mo (r, 0.3-17.6) for TPC. Exposure-adjusted incidence rates (EAIRs; per pt-y) for any-grade TEAEs were lower for T-DXd vs TPC (1.30 vs 2.66). mTTO and mDUR of any-grade interstitial lung disease (ILD) in pts treated with T-DXd were 129 days (d; r, 26-710 d) and 47 d (r, 13-365 d). 13 pts had adjudicated drug-related grade 1 ILD; of those pts, 6 were rechallenged with T-DXd after resolution (details to be presented). Incidence of any-grade drug-related neutropenia (NP) and febrile NP was lower for T-DXd vs TPC; subsequent granulocyte colony-stimulating factor use was 6.7% vs 19.8%. Nausea/vomiting (N/V) events in T-DXd vs TPC were 79.5% vs 35.5%. T-DXd-treated pts received more antiemetic prophylaxis (AP; 50.9%) vs TPC-treated pts (37.2%); 92.3% of T-DXd and 68.8% of TPC N/V events in AP-treated pts resolved. Incidence of any-grade drug-related TEAE was consistent between pts aged <65 y and ≥65 y. For T-DXd, incidence of grade ≥3 TEAEs and TEAEs associated with drug discontinuations (DD) was higher in pts aged ≥65 y compared to those aged <65 y; the most common TEAE associated with DD was ILD/pneumonitis. However, mPFS favored T-DXd over TPC in all patients, regardless of age. EAIR, TTO, and DUR data for selected TEAEs will be presented.
T-DXd demonstrated a manageable safety profile to support its use as the new standard of care in pts with HER2-low mBC.
NCT03734029.
Under the guidance of authors, assistance in medical writing and editorial support was provided by Elize Wolmarans, PhD, and Soniya Patel, PhD, of ApotheCom, and was funded by Daiichi Sankyo, Inc.
Daiichi Sankyo, Inc., and AstraZeneca.
This study was funded by Daiichi Sankyo, Inc., and AstraZeneca.
H.S. Rugo: Financial Interests, Personal, Advisory Role, Consultancy: Puma, NAPO, Blueprint, Scorpion Therapeutics; Financial Interests, Personal, Invited Speaker, Travel Expenses, including accommodations: Merck, AstraZeneca, Gilead; Other, Institutional, Research Grant: Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo, Inc., F. Hoffmann-La Roche AG/Genentech Inc., Gilead Sciences, Inc., GlaxoSmithKline, Lilly, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, OBI Pharma, Pfizer, Pionyr Immunotherapeutics, Sermonix Pharmaceuticals Inc., Taiho Oncology, Inc., Veru Inc. W. Jacot: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, Novartis, Roche, Pfizer, Eli Lilly, MSD, BMS, Chugai, Seagen, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi Sankyo; Financial Interests, Invited Speaker: Roche, Novartis, Daiichi Sankyo, Daiichi Sankyo. E. Tokunaga: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Eli Lilly, Daiichi Sankyo. J. Sohn: Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo; Financial Interests, Personal, Research Grant: Seagen, MSD, Roche, Novartis, AstraZeneca, Lilly, Pfizer, GlaxoSmithKline, Daiichi Sankyo, Inc., Sanofi, Boehringer Ingelheim. F. Cardoso: Financial Interests, Personal, Other, Consultancy: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Medscape, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, Prime Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva; Financial Interests, Personal, Advisory Board: Gilead, Iqvia, Touchime; Financial Interests, Institutional, Invited Speaker: Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Bayer, Daiichi, Eisai, Fresenius GmbH, Genentech, GlaxoSmithKline, Ipsen, Incyte, Nektar Therapeutics, Nerviano, Novartis, Macrogenics, Medigene, MedImmune, Merck, Millenium, Pfizer, Pierre-Fabre, Roche, Sanofi-Aventis, Sonus, Taiho Oncology, Tesaro, Tigris, Wilex, Wyeth, Gilead; Non-Financial Interests, Leadership Role, President: ABC Global Alliance and ABC Consensus Conference and Guidelines; Non-Financial Interests, Member: ESMO, ESO, EORTC, BCG, IBCSG, SOLTI, ASCO, AACR, EACR, SIS, ASPIC. B. Xu: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer, Roche; Financial Interests, Institutional, Research Grant: Henrui. M.J. Gil: Financial Interests, Personal, Invited Speaker, Honoraria: AstraZeneca, Novartis, Pfizer, Pierre-Fabre, Roche; Financial Interests, Personal, Advisory Role, Advisory/ Consultancy: Daiichi Sankyo, Seagen, Gilead; Financial Interests, Personal, Advisory Board, Travel Expenses, including accommodations: Daiichi Sankyo, Pfizer. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, BMS, Puma, Oncolytics Biotech, MSD, Guardant Health, Peptomyc; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Institutional, Other, Contracted research: Boehringer, Medica Scientia inno. Research; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics, Oncolytics Biotech; Financial Interests, Personal, Royalties: Reveal Genomics; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation, Actitud Frente al Cáncer Foundation. H. Moore: Financial Interests, Personal, Advisory Role, Consulting Fees: Myovant; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Daiichi Sankyo, Sermonic, Seagen. U. Hasler-Strub: Financial Interests, Personal, Other, Travel Expenses, including accommodations: Daiichi Sankyo. D.A.A. Cameron: Financial Interests, Personal, Advisory Role, Consultancy: Seagen, Daiichi Sankyo, AstraZeneca, Synthon, Novartis, GSK. H. Lindman: Financial Interests, Personal, Invited Speaker, Honoraria: Lilly, AstraZeneca, Daiichi Sankyo, Pierre Fabre; Financial Interests, Personal, Advisory Role, Consultancy: Lilly, MSD, Daiichi Sankyo, Novartis, Seagen, Gilead, AstraZeneca; Financial Interests, Personal, Research Grant: Roche. R. Rajagopalan, C.M.A. Orbegoso, F. Cheng, A. Puri: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. S. Modi: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Genentech, AstraZeneca, Seagen, Macrogenics; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, Genentech, AstraZeneca, Seagen. All other authors have declared no conflicts of interest.
In DESTINY-Breast02 (NCT03523585), T-DXd improved progression-free and overall survival vs TPC in pts with HER2+ mBC who were resistant/refractory to trastuzumab emtansine (T-DM1) (Krop et al. SABCS 2022). Here, we report data on PROs and health-related quality of life (QoL).
Pts with HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization amplified) T-DM1–resistant/refractory mBC were assigned 2:1 to T-DXd or TPC (trastuzumab + capecitabine or lapatinib + capecitabine). PROs were collected and measured at prespecified timepoints using the European Organization for Research and Treatment of Cancer QoL questionnaires (EORTC QLQ)-C30, the breast-cancer–specific EORTC QLQ-BR45 (scored as EORTC QLQ-BR23), and the EuroQol 5-dimension 5-level (EQ-5D-5L) visual analog scale. Change from baseline (CFB) and time to definitive deterioration (TDD) were assessed. QLQ-C30 global health status (GHS)/QoL score was the primary variable of interest.
In the T-DXd (n = 406) and TPC (n = 202) arms (median treatment duration of the safety analysis set: 11.3 vs ∼4.5 mo), questionnaire compliance was >92% at baseline and >76% at cycles 3-29. Mean CFB of GHS/QoL remained stable (within ±10 points) up to cycle 39 for T-DXd and cycle 21 for TPC, after which the number of pts on treatment was not informative (n < 10%). Median TDD was longer with T-DXd vs TPC for GHS/QoL (14.1 vs 5.9 mo; HR, 0.56 [95% CI, 0.44-0.71]) and for all measured QLQ-C30 subscales, including physical functioning (18.7 vs 6.8 mo; HR, 0.46 [95% CI, 0.36-0.60]) and pain (18.7 vs 5.8 mo; HR, 0.38 [95% CI, 0.29-0.49]), with the exception of nausea/vomiting (5.7 vs 6.1 mo; HR, 1.09 [95% CI, 0.86-1.39]). With T-DXd vs TPC, pts experienced prolonged TDD on the QLQ-BR23 arm symptom subscale (18.3 vs 8.8 mo; HR, 0.57 [95% CI, 0.44-0.75]).
Mean CFB in GHS/QoL suggested that overall health and QoL were maintained in T-DXd-treated pts. TDD was longer on all measured QLQ-C30 subscales, except for nausea/vomiting, for pts receiving T-DXd vs TPC. These results continue to support the benefit of T-DXd in pts with T-DM1–resistant HER2+ mBC.
NCT03523585.
Under the guidance of authors, assistance in medical writing and editorial support was provided by Caylin Bosch, PhD, and Toinette Labuschagné, PhD, of ApotheCom, and was funded by Daiichi Sankyo, Inc.
Daiichi Sankyo, Inc., and AstraZeneca.
This study was funded by Daiichi Sankyo, Inc., and AstraZeneca. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201).
T.N. Fehm: Financial Interests, Personal, Other, Honoraria: Onkowissen, Medconcept; Financial Interests, Institutional, Other, Honoraria: Novartis, Pfizer, Daiichi Sankyo, Roche, Stemlines, MSD, Pierre Fabre, AstraZeneca. F. Cottone, K. Dunton: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. F. André: Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi; Financial Interests, Institutional, Other, advisory board: Guardant Health; Financial Interests, Institutional, Other, Advisory board: MEDIMMUNE, Gilead, Relay therapeutics; Other, Founder: Pegacsy. I. Krop: Financial Interests, Personal, Advisory Board: Genentech/Roche, AstraZeneca, Daiichi Sankyo, Macrogenics, Seagen; Financial Interests, Personal, Other, DSMB member: Novartis; Financial Interests, Personal, Other, DSMC member: Merck; Financial Interests, Personal, Full or part-time Employment, Spouse: PureTech, Freeline; Financial Interests, Personal, Stocks/Shares, Spouse: PureTech, Freeline; Financial Interests, Institutional, Invited Speaker: Pfizer, Macrogenics, Genentech, Roche. Y.H. Park: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Lilly, MSD, Eisai, Roche, Daiichi Sankyo, Menarini, Bixink; Financial Interests, Personal, Research Grant: MSD, AstraZeneca, Roche, Pfizer, Novartis; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. M. De Laurentiis: Financial Interests, Personal, Invited Speaker: Novartis, Roche, Lilly, MSD, Daiichi Sankyo, AstraZeneca, Pfizer, Menarini, GSK, Gilead; Financial Interests, Personal, Advisory Board: Novartis, Roche, Eli Lilly, MSD, Daiichi Sankyo, AstraZeneca, GSJ, Menarini, Gilead, Seagen. Y. Miyoshi: Financial Interests, Personal, Speaker’s Bureau: Chugai, Eli Lilly, Daiichi Sankyo, Taiho, MAD, Kyowa-Kirin, Eisai, AstraZeneca; Financial Interests, Institutional, Research Grant: Chugai, Eli Lilly, Daiichi Sankyo, Taiho, MAD, Kyowa-Kirin, Eisai, AstraZeneca. A. Armstrong: Financial Interests, Personal, Advisory Board: MSD, Gilead; Financial Interests, Personal, Stocks/Shares, Spouse Shares: AstraZeneca; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Personal, Other, Travel: MSD, Gilead; Financial Interests, Invited Speaker, Travel: Novartis. R. Yerushalmi: Financial Interests, Personal, Invited Speaker: Roche, Teva, Medison, MSD, Astra-Zeneca; Financial Interests, Personal, Advisory Board: Roche, Pfizer, Novartis, AstraZeneca, Gilead. F.P. Duhoux: Financial Interests, Personal, Other, Honoraria: Roche, Pfizer, Lilly, AstraZeneca, Novartis, Amgen, Daiichi Sankyo, Pierre Fabre; Financial Interests, Personal, Other, Travel: Daiichi Sankyo, Gilead, Pfizer, Roche; Financial Interests, Personal, Research Grant: Fondation Belge contre le Cancer. T. Takano: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Chugai, Eli Lilly. W. Lu: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. C. Livings: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Egorov: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. S. Kim: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Lilly, DaeHwa Pharma, ISU Abx, Daiich-Sankyo, Beigene, HLB Life Science, Samsung Bioepics, OBI pharma; Financial Interests, Personal, Invited Speaker: Legochem Bioscience; Financial Interests, Personal, Ownership Interest: Genopeaks, Neogene TC; Financial Interests, Institutional, Research Grant: Novartis, Sanofi-Genzyme, DongKook Pharm Co. All other authors have declared no conflicts of interest.
Capivasertib is a potent, selective pan-AKT inhibitor. In the phase III CAPItello-291 trial in pts with AI-resistant, HR+/HER2– ABC, the addition of capivasertib to fulvestrant (fulv) significantly improved the dual primary endpoints of PFS in the overall (hazard ratio [HR] 0.60; 95% confidence interval [CI] 0.51–0.71; p<0.001) and AKT pathway-altered population (HR 0.50; 95% CI 0.38–0.65; p<0.001) compared with placebo plus fulv. Here we report PFS in key clinically relevant subgroups (data cut-off Aug 15, 2022).
Pts were randomised 1:1 to receive fulv (500 mg IM on days 1 and 15 of cycle 1, and day 1 of each subsequent 28-day cycle) with either placebo or capivasertib (400 mg twice daily; 4 days on, 3 days off). Randomisation was stratified by the presence of liver metastases, prior use of CDK4/6 inhibitor (CDK4/6i) and region. Preplanned exploratory PFS analyses included prior use of CDK4/6i, prior chemotherapy (CT) for ABC, and presence of liver metastases.
Overall, 708 pts were randomised to capivasertib-fulv (n=355) or placebo-fulv (n=353): 289 pts (40.8%) had AKT pathway-altered tumours; 496 pts (70.1%) had received prior CDK4/6i; 129 pts (18.2%) had received prior CT for ABC, and 306 pts (43.2%) had liver metastases. PFS benefit of capivasertib-fulv over placebo-fulv was broadly consistent across key clinical subgroups (Table). In cross-subgroup comparison, placebo-fulv efficacy was lower in pts with prior CDK4/6i exposure and pts with liver metastases. Findings in the AKT pathway-altered population were consistent with the overall population and will be presented. PFS in the overall population
n Median PFS, months (95% CI) HR (95% CI) (unadjusted) Capivasertib-fulv Placebo-fulv Prior CDK4/6i Yes 496 5.5 (3.9–6.8) 2.6 (2.0–3.5) 0.62 (0.51–0.75) No 212 10.9 (7.4–13.0) 7.2 (4.8–7.9) 0.65 (0.47–0.91) Prior CT for ABC Yes 129 3.8 (3.0–7.3) 2.1 (1.9–3.6) 0.61 (0.41–0.91) No 579 7.3 (5.6–8.2) 3.7 (3.4–5.1) 0.65 (0.54–0.78) Liver metastases Yes 306 3.8 (3.5–5.5) 1.9 (1.8–1.9) 0.61 (0.48–0.78) No 402 9.2 (7.4–11.1) 5.5 (3.9–5.8) 0.62 (0.49–0.79)
Exploratory PFS analyses confirmed a consistent benefit of treatment with capivasertib-fulv vs fulv alone in clinically relevant subgroups, including pts with prior CDK4/6i exposure or liver metastases, subgroups with poor prognosis on fulv alone.
NCT04305496, Actual Primary Completion Date: August 15, 202.2 Estimated Study Completion Date: June 7, 2024.
AstraZeneca-funded medical writing support was provided by Suzanne Patel, Ph.D., from BOLDSCIENCE Inc. Capivasertib was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).
AstraZeneca.
AstraZeneca.
M. Oliveira: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo / AstraZeneca, GSK, Gilead, PUMA Biotechnology, Pierre Fabre, Roche, Seagen, iTEOS, MSD; Financial Interests, Personal, Invited Speaker: Eisai, Gilead, Guardant Health, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Seattle Genetics, AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer-Ingelheim, GSK, Genentech, Immunomedics, Novartis, Roche, Seattle Genetics, Zenith Epigenetics, Gilead; Financial Interests, Invited Speaker: Roche; Non-Financial Interests, Invited Speaker: SOLTI Breast Cancer Research; Other, Travel Grant: Pierre Fabre, Roche, Novartis, Eisai. H.S. Rugo: Financial Interests, Personal, Advisory Role: Napo Pharmaceuticals, Scorpion Therapeutics, Blueprint Medicines, Puma Biotechnology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck, AstraZeneca, Gilead Sciences; Financial Interests, Institutional, Funding: OBI Pharma, Pfizer, Novartis, Lilly, Genentech, Merck, Daiichi Sankyo, Sermonix Pharmaceuticals, AstraZeneca, Gilead Sciences, Astellas Pharma, Pionyr, Taiho Oncology, Veru; Financial Interests, Institutional, Invited Speaker: GlaxoSmithKline. S.J. Howell: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Advisory Board: Pfizer. F. Dalenc: Non-Financial Interests, Institutional, Advisory Role: AstraZeneca, Daiichi, Pfizer, Seagen, Gilead, Novartis. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, MERCK SHARP& DOHME, GSK, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, MERCK SHARP& DOHME, Daiichi Sankyo; Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca. H.L. Gomez Moreno: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Roche, Novartis, AstraZeneca, Bristol Myers Squibb, Lilly; Financial Interests, Personal, Funding: MSD Oncology. X. Hu: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Novartis, Pfizer. K. Jhaveri: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Pfizer, Genentech/Roche, Lilly/Loxo Oncology, BMS, Scorpion Therapeutics, Biotheranostics, Blueprint Medicines, Taiho Oncology, Jounce Therapeutics, Seattle Genetics, Daiichi Sankyo, AbbVie, Olema, Pharmaceuticals, Sun Pharma Advanced, Research Company Ltd., Menarini/Stemline, Eisai; Financial Interests, Institutional, Funding: Novartis, AstraZeneca, Pfizer, Genentech/Roche, Lilly/Loxo Oncology, Merck, PUMA Biotechnology, Zymeworks, Gilead, Context Therapeutics. S. Loibl: Financial Interests, Institutional, Advisory Board, Member: Amgen, AstraZeneca, BMS, Celgene, EirGenix, GSK, Lilly, Pierre Fabre, Roche, Seagen, AbbVie, Sanofi, Gilead, Merck, Novartis, Relay Therapeutics; Financial Interests, Institutional, Invited Speaker: AstraZeneca, DSI, Novartis, Pfizer, Roche, Gilead, Seagen; Financial Interests, Institutional, Advisory Board: DSI, Pfizer, Olema; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Personal, Full or part-time Employment, CEO: GBG Forschungs GmbH; Financial Interests, Institutional, Invited Speaker, Ki67: VM Scope GmbH; Financial Interests, Institutional, Research Grant: AstraZeneca, Celgene, Novartis, Immunomedics/Gilead, Pfizer, Roche, Daiichi Sankyo; Financial Interests, Institutional, Funding: AbbVie, Molecular Health; Financial Interests, Personal, Other, PIPenelope/Padma: Pfizer; Financial Interests, Personal, Other, SC PALOMA3: Pfizer; Financial Interests, Personal, Other, SC SOLAR1: Novartis; Financial Interests, Personal, Other, SC ASCENT: Immunomedics/Gilead; Financial Interests, Personal, Other, SC HERCLIMB: Seagen; Financial Interests, Personal, Other, SC Katherine: Roche; Financial Interests, Personal, Other, SC Capitello; EC Cambria 1: AstraZeneca; Financial Interests, Personal, Other, SC Inavo: Roche; Financial Interests, Personal, Other, SC Destiny B05; SC Destiny B09: Daiichi Sankyo; Non-Financial Interests, Principal Investigator, After publication of primary endpoint: PI Aphinity; Non-Financial Interests, Advisory Role, Group in Germany responsible for breast cancer guidelines: AGO Kommission Mamma; Non-Financial Interests, Member, German Gynaecological Oncology society: AGO; Non-Financial Interests, Member, German Cancer Society: DKG; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member, Member guideline committee; past chair in ESMO Breast: ESMO; Other, EP14153692.0No financial interest, Institutional: Patent; Other, EP21152186.9No financial interest, institutional: Patent; Other, EP15702464.7No financial interest, institutional: Patent; Other, EP19808852.8 No financial interest, Institutional: Patent. Y.H. Park: Financial Interests, Personal and Institutional, Writing Engagements: Novartis, Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal and Institutional, Advisory Board: Novartis, Pfizer, Merck, Roche, Lilly, AstraZeneca , Daiichi Sankyo, Gilead Sciences, Boryung; Financial Interests, Personal and Institutional, Principal Investigator: Novartis, Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo, Gilead Sciences, Boryung; Non-Financial Interests, Personal and Institutional, Writing Engagements: Novartis, Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo; Non-Financial Interests, Personal and Institutional, Advisory Board: Novartis, Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo; Non-Financial Interests, Personal and Institutional, Principal Investigator: Novartis, Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal and Institutional, Research Grant: Pfizer, Roche, Lilly, AstraZeneca; Non-Financial Interests, Personal and Institutional, Invited Speaker: Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo; Non-Financial Interests, Personal and Institutional, Research Grant: Pfizer, Merck, Roche, Lilly, AstraZeneca; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Eisai, Menarini; Financial Interests, Personal, Principal Investigator: Menarini; Financial Interests, Institutional, Research Grant: Gencurix, Genome Insight, NGenbio; Financial Interests, Institutional, Principal Investigator: Gencurix. J. Sohn: Financial Interests, Personal, Stocks/Shares, Immediate Family Member: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: MSD, Roche, Novartis, AstraZeneca, Lilly, Pfizer, GSK, Daiichi Sankyo, Sanofi, Boehringer Ingelheim, Seagen. E. Tokunaga: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Eli Lilly, Daiichi Sankyo. L. Zhukova: Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Novartis, Biocad. I. Wadsworth: Financial Interests, Personal and Institutional, Other, Paid employee for Phastar and contracted to work full time for AstraZeneca as a statistician.: AstraZeneca. G. Schiavon: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Foxley: Financial Interests, Personal, Full or part-time Employment, Employee: AstraZeneca; Financial Interests, Personal, Stocks/Shares, Stock as part of remuneration for employment: AstraZeneca. N. Turner: Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Pfizer, Bristol Myers Squibb, Merck Sharp & Dohme, Lilly, Repare Therapeutics, Zeno pharmaceuticals, Roche, Inivata; Financial Interests, Institutional, Funding: Pfizer, Roche, AstraZeneca, Clovis Oncology, Bio-Rad, Guardant Health, Inivata, InVitae, Personalis, Natera. All other authors have declared no conflicts of interest.
The phase III EMERALD trial (NCT03778931) reported significantly prolonged progression-free survival (PFS) and a manageable safety profile with elacestrant vs SoC endocrine therapy (ET) in patients (N=478) with ER+/HER2− advanced or mBC following progression on prior CDK4/6i plus ET. PROs measuring quality of life (QoL) are reported here.
EMERALD patients (pts) completed 3 PRO tools at prespecified time points: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), the PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and the EuroQoL 5 Dimension 5 Level (EQ-5D-5L).
The ratio of PROs tools completed vs. PROs tools expected was 80-90% through cycle 4 and approximately 70% at cycle 6; likely due to clinical study period overlapping with COVID-19 period. Overall, the EORTC QLQ-C30 scores were similar for elacestrant and SoC, with no differences across all time points for both functional and symptom scales. However, PRO-CTCAE results showed that fewer pts who received elacestrant reported very severe nausea (4.0% vs 14.3% by cycle 6) or very severe vomiting (9.1% vs 50% by cycle 6) compared with SoC. There were no clinically meaningful differences across all time points in adverse events typically observed with pts with cancer on ET, such as fatigue, nausea, vomiting, joint and muscle pain and hot flashes. EQ-5D-5L scores were generally comparable throughout treatment for both study arms, with elacestrant showing numerically better outcomes vs SoC for mobility, self-care and usual activities. Similar trends were observed for the full intent-to-treat population and in pts with detectable estrogen receptor 1 mutations (
This analysis confirmed that QoL was maintained between treatment groups in the EMERALD trial. Together with the previously described statistically significant prolonged PFS and manageable safety profile, these PRO results provide additional evidence that oral elacestrant is clinically meaningful in this patient population with limited therapeutic options.
NCT03778931.
Jeffrey Walter, IQVIA.
Stemline Therapeutics/Menarini Group.
Stemline Therapeutics/Menarini Group.
J. Cortés: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, MERCK SHARP& DOHME, GSK, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, MERCK SHARP& DOHME, Daiichi Sankyo; Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardant Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca. F.C. Bidard: Financial Interests, Personal, Advisory Role: Pfizer, AstraZeneca, Lilly, Novartis, Radius Health, Menarini; Financial Interests, Institutional, Advisory Role: Menarini; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Novartis, AstraZeneca, Roche, Lilly, Rain Therapeutics; Financial Interests, Institutional, Research Grant: Novartis, Pfizer, Menarini Silicon Biosystems, Prolynx; Financial Interests, Institutional, Other, patents: ESR1 & MSI detection techniques; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, Pfizer, AstraZeneca, Novartis. A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Genentech, Merck, Sanofi, Eisai, Lilly, Mersana, AstraZeneca/Daiichi, Menarini, Gilead; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Invited Speaker: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly.; Non-Financial Interests, Principal Investigator: Gilead, Mersana, AstraZeneca/Daiichi, Novartis, Pfizer, Genentech, Lilly, Merck, Sanofi. V.G. Kaklamani: Financial Interests, Personal, Other, Honoraria: Genentech, Novartis, Pfizer, Genomic Health, Puma Biotechnology, AstraZeneca, Seattle Genetics, Daichi, Gilead Sciences; Financial Interests, Personal, Advisory Role: Amgen, Eisai, Puma Biotechnology, Celldex, AstraZeneca, Athenex, bioTheranostics; Financial Interests, Personal, Speaker’s Bureau: Genentech, Novartis, Genomic Health, Puma Biotechnology, Pfizer, AstraZeneca/Daiichi Sankyo; Financial Interests, Personal, Research Grant: Eisai. I. Vlachaki: Financial Interests, Personal, Full or part-time Employment: Menarini Hellas A.E. G. Tonini: Financial Interests, Personal, Full or part-time Employment: Menarini Ricerche S.p.A. N. Habboubi: Financial Interests, Personal, Full or part-time Employment: Stemline Therapeutics; Financial Interests, Personal, Leadership Role: Stemline Therapeutics. P.G. Aftimos: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure, Servier, G1 Therapeutics, Radius, Deloitte, Menarini, Gilead, Novartis, Eisai, Lilly; Financial Interests, Personal, Invited Speaker: Synthon, Amgen; Financial Interests, Institutional, Research Grant: Roche.