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LBA15 - Primary outcome of the phase III SYD985.002/TULIP trial comparing [vic-]trastuzumab duocarmazine to physician’s choice treatment in patients with pre-treated HER2-positive locally advanced or metastatic breast cancer
- Cristina Saura Manich (Barcelona, Spain)
Abstract
Background
[vic-]Trastuzumab duocarmazine (SYD985, Byondis B.V., NL) is a novel HER2-targeting antibody–drug conjugate comprised of trastuzumab bound to a linker drug containing duocarmycin. TULIP assessed the efficacy of SYD985 in advanced HER2-positive breast cancer.
Methods
The TULIP trial (NCT03262935) randomly assigned HER2-positive locally advanced or metastatic breast cancer (MBC) patients with ≥ 2 previous MBC regimens or previous MBC treatment with T-DM1, 2:1 between SYD985 (1.2 mg/kg q three weeks) and physician’s choice (PC) chemotherapy. The primary endpoint was progression-free survival (PFS) by blinded central review. The trial was powered to detect a Hazard Ratio (HR) of 0.65 at the P < 0.05 significance level. Secondary endpoints were investigator-assessed PFS, overall survival (OS), objective response rate (ORR), and health-related quality of life (HRQoL).
Results
437 patients from 11 countries were randomized to SYD985 (n=291) or PC (n=146). Median age was 56 years, median number of prior MBC treatments was 4 [range 1-16]. Centrally reviewed median PFS was 7.0 months [95% CI 5.4-7.2] for SYD985 and 4.9 mo [4.0-5.5] for PC (HR 0.64 [0.49-0.84]; p = 0.002). Investigator-assessed PFS was also significantly improved (6.9 mo [6.0-7.2] vs 4.6 mo [4.0-5.6]; HR 0.60 [0.47-0.77]; p < 0.001). In this first analysis of OS the HR was 0.83 [0.62-1.09]; p = 0.153. No significant differences were observed in ORR or HRQoL. The most frequently reported adverse events for SYD985 were conjunctivitis (38.2%), keratitis (38.2%) and fatigue (33.3%), for PC these were diarrhoea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease / pneumonitis was reported for 7.6% (5.2% grade 1-2) of patients treated with SYD985, including two grade 5 events. Adverse events leading to discontinuation (SYD985 35.4%, PC 10.2%) in the SYD985 group were mainly related to eye disorders (20.8%) or respiratory disorders (6.3%).
Conclusions
Treatment with SYD985 significantly improved PFS in comparison with standard PC and may provide a new treatment option for patients with pre-treated locally advanced or metastatic HER2-positive MBC.
Clinical trial identification
NCT03262935.
Legal entity responsible for the study
Byondis B.V., Nijmegen, The Netherlands.
Funding
Byondis B.V.
Disclosure
C. Saura Manich: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Advisory Board: Exeter Pharma; Financial Interests, Personal, Advisory Board: F. Hoffmann - La Roche Ltd; Financial Interests, Personal, Advisory Board: MediTech; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Philips; Financial Interests, Personal, Advisory Board: Piere Fabre; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: Roche Farma; Financial Interests, Personal, Advisory Board: Sanofi Aventis; Financial Interests, Personal, Advisory Board: SeaGen; Financial Interests, Personal, Advisory Board: Zymeworks; Financial Interests, Personal, Other, SC: Byondis B.V.; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Eli Lilly and Company; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Macrogenics; Financial Interests, Institutional, Research Grant: Merck, Sharp and Dhome España S.A.; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Piqur Therapeutics; Financial Interests, Institutional, Research Grant: Puma; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Synthon; Financial Interests, Institutional, Research Grant: Zenith Pharma; Financial Interests, Institutional, Invited Speaker: Byondis B.V.; Non-Financial Interests, Member: Spanish Society of Medical Oncology (SEOM); Non-Financial Interests, Member: American Society for Clinical Oncology (ASCO); Non-Financial Interests, Member: SOLTI group (Academic research group in breast cancer); Non-Financial Interests, Member: Geicam (Spanish Breast Cancer Research Group); Non-Financial Interests, Member: American Association for Cancer Research (AACR). J. O'Shaughnessy: Financial Interests, Personal, Advisory Board: AbbVie Inc; Financial Interests, Personal, Advisory Board: Agendia; Financial Interests, Personal, Advisory Board: Aptitude Health; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Celgene Corporation; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: G1 Therapeutics; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Gilead Sciences; Financial Interests, Personal, Advisory Board: GRAIL; Financial Interests, Personal, Advisory Board: Halozyme Therapeutics; Financial Interests, Personal, Advisory Board: Heron Therapeutics; Financial Interests, Personal, Advisory Board: Immunomedics; Financial Interests, Personal, Advisory Board: Ipsen Biopharmaceuticals; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Myriad; Financial Interests, Personal, Advisory Board: Nektar Therapeutics; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Ontada; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Pharmacyclics; Financial Interests, Personal, Advisory Board: Pierre Fabre Pharmaceuticals; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Financial Interests, Personal, Advisory Board: Prime Oncology; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Samsung Bioepis; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: Syndax Pharmaceuticals; Financial Interests, Personal, Advisory Board: Taiho Oncology; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Synthon B.V.; Financial Interests, Personal, Advisory Board: Byondis B.V. P.G. Aftimos: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Macrogenics; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Amcure; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: G1 Therapeutics; Financial Interests, Personal, Advisory Board: Radius; Financial Interests, Personal, Advisory Board: Deloitte; Financial Interests, Personal, Advisory Board: Menarini; Financial Interests, Personal, Advisory Board: Synthon; Financial Interests, Personal, Advisory Board: Byondis; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Role: Gilead; Non-Financial Interests, Personal, Other, Travel grant: MSD; Non-Financial Interests, Personal, Other, Travel grant: Pfizer; Financial Interests, Institutional, Funding: Roche; Financial Interests, Personal, Advisory Board: Sanofi-Aventis; Non-Financial Interests, Personal, Other, Travel grant: Roche; Non-Financial Interests, Personal, Other, Travel grant: Amgen; Non-Financial Interests, Personal, Other, Member of the scientific committee: IBCSG. E. van den Tweel: Financial Interests, Personal, Full or part-time Employment: Byondis B.V.; Non-Financial Interests, Personal, Member: ESMO; Non-Financial Interests, Personal, Member: ASCO. M. Oesterholt: Financial Interests, Personal, Full or part-time Employment: Byondis B.V. S.I. Escrivá-de-Romaní: Financial Interests, Personal, Invited Speaker, Advisory board, Travel grants: Roche; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Advisory Board, Invited speaker, travel grants: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Invited speaker, travel grant: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Research Grant: Zymeworks; Financial Interests, Institutional, Research Grant: Synthon B.V.; Financial Interests, Institutional, Research Grant: Byondis B.V.; Financial Interests, Personal, Advisory Board: Seagen. N. Quenel Tueux: Financial Interests, Institutional, Principal Investigator: Byondis B.V. T.J. Tan: Financial Interests, Personal and Institutional, Advisory Board, Invited speaker, Board & Principal Investigator: Novartis; Financial Interests, Personal and Institutional, Advisory Board, Principal Investigator: Roche; Financial Interests, Personal, Speaker’s Bureau, Advisory board: DKSH; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker, Advisory board: MSD; Financial Interests, Personal and Institutional, Invited Speaker, Advisory board, Principal Investigator, Research grant: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator: Seagen. J.S. Lim: Financial Interests, Personal, Invited Speaker, Advisory board: AstraZeneca; Financial Interests, Personal, Advisory Board, Invited speaker: DKSH; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Roche; Non-Financial Interests, Institutional, Funding: CTI Biopharma; Non-Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo; Non-Financial Interests, Institutional, Principal Investigator: Byondis B.V.; Non-Financial Interests, Institutional, Principal Investigator: Synthon B.V.; Non-Financial Interests, Institutional, Principal Investigator: Taiho Pharmaceuticals. S. Ladoire: Financial Interests, Institutional, Principal Investigator: Byondis B.V. A. Armstrong: Financial Interests, Institutional, Principal Investigator: Byondis B.V. T. Crook: Financial Interests, Institutional, Principal Investigator: Byondis B.V.; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Daiichi Sankyo. A. Stradella: Financial Interests, Institutional, Principal Investigator: Byondis B.V.; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal and Institutional, Expert Testimony: Seagen. G. Bianchi: Financial Interests, Institutional, Principal Investigator: Byondis B.V.; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche. R. Mulder: Financial Interests, Personal, Full or part-time Employment: Byondis B.V. N. Koper: Financial Interests, Personal, Full or part-time Employment: Byondis B.V. N. Turner: Financial Interests, Institutional, Principal Investigator: Byondis B.V.; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck Sharpe and Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche/Genentech; Financial Interests, Personal, Advisory Board: Bicycle Therapeutics; Financial Interests, Personal, Advisory Board: Taiho; Financial Interests, Personal, Advisory Board: Zeno Phamraceuticals; Financial Interests, Personal, Advisory Board: Repare therapeutics; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: BioRad; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Roche/Genentech; Financial Interests, Institutional, Funding: Clovis; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Guardant Health; Non-Financial Interests, Personal, Advisory Board: Byondis B.V.
Invited Discussant LBA15
- Barbara Pistilli (Villejuif, France)
Q&A and live discussion
- Barbara Pistilli (Villejuif, France)
LBA16 - KEYNOTE-355: Final results from a randomized, double-blind phase III study of first-line pembrolizumab + chemotherapy vs placebo + chemotherapy for metastatic TNBC
- Hope S. Rugo (San Francisco, CA, United States of America)
Abstract
Background
A prior interim analysis of KEYNOTE-355 (NCT02819518) showed that first-line pembrolizumab (pembro) + chemotherapy (chemo) significantly improved PFS vs placebo (pbo) + chemo in patients (pts) with metastatic TNBC whose tumors expressed PD-L1 (CPS ≥10) (HR, 0.65, 95% CI, 0.49–0.86; one-sided
Methods
847 pts with de novo metastasis or ≥6 mo DFI were randomized 2:1 to pembro + chemo (nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin) or pbo + chemo for up to 35 administrations of pembro/pbo or until progression/intolerable toxicity. Pts were stratified by chemo type (taxane or gemcitabine-carboplatin), PD-L1 status (CPS ≥1 or <1) and prior (neo)adjuvant treatment with same-class chemo (yes or no). Dual primary endpoints are PFS (RECIST v1.1 by BICR) and OS in pts with PD-L1+ tumors (CPS ≥10 and ≥1) and all pts (ITT). ORR is a secondary endpoint. AEs were monitored throughout the study and graded per NCI CTCAE v4.0.
Results
As of June 15, 2021, median follow-up was 44.1 mo. Pembro + chemo significantly improved OS vs chemo alone in pts with CPS ≥10 tumors (
Conclusions
Pembro + chemo showed a statistically significant and clinically meaningful improvement in OS vs chemo alone in pts with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1 (CPS ≥10). No new safety signals were identified. aFrom Kaplan-Meier method.bFrom a stratified Cox model.c
CPS ≥10 CPS ≥1 ITT P + C C P + C C P + C C OS, mo, mediana 23.0 (19.0 – 26.3) 16.1 (12.6 – 18.8) 17.6 (15.5 – 19.5) 16.0 (12.8 – 17.4) 17.2 (15.3 – 19.0) 15.5 (13.9 – 17.2) OS, HRb 0.73c (0.55 – 0.95) 0.86d (0.72 – 1.04) 0.89 (0.76 – 1.05) PFS, mo, mediana 9.7 (7.6 – 11.3) 5.6 (5.3 – 7.5) 7.6 (6.6 – 8.0) 5.6 (5.4 – 7.4) 7.5 (6.3 – 7.7) 5.6 (5.4 – 7.2) PFS, HRb 0.66 (0.50 – 0.88) 0.75 0.62 – 0.91 0.82 0.70 – 0.98 ORR, % 52.7 (45.9 – 59.5) 40.8 (31.2 – 50.9) 44.9 (40.1 – 49.8) 38.9 (32.2 – 45.8) 40.8 (36.7 – 45.0) 37.0 (31.4 – 42.9)
Clinical trial identification
NCT02819518.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Christine McCrary Sisk. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
J. Cortés: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Celestial; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Biothera Pharmaceutical; Financial Interests, Personal, Advisory Role: Merus; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Erytech; Financial Interests, Personal, Advisory Role: Athenex; Financial Interests, Personal, Advisory Role: Polyphor; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: Leuko; Financial Interests, Personal, Advisory Role: Bioasis; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Kyowa Kirin; Financial Interests, Personal, Advisory Role: 4D Pharma PLC; Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Funding: Novartis; Financial Interests, Personal, Funding: Celgene; Financial Interests, Personal, Funding: Eisai; Financial Interests, Personal, Funding: Pfizer; Financial Interests, Personal, Funding: Samsung Bioepis; Financial Interests, Personal, Funding: Lilly; Financial Interests, Personal, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Funding: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Ariad Pharmaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Baxalta GMBH/Servier Affaires; Financial Interests, Institutional, Research Grant: Bayer Healthcare; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: F. Hoffmann-La Roche; Financial Interests, Institutional, Research Grant: Guardanth Health; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Piqur Therapeutics; Financial Interests, Institutional, Research Grant: Puma C; Financial Interests, Institutional, Research Grant: Queen Mary University of London; Financial Interests, Personal, Stocks/Shares: MedSIR; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Roche; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Novartis; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Eisai; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Daiichi Sankyo. D.W. Cescon: Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Funding: GlaxoSmithKline, Inivata, Merck, Pfizer, Roche; Non-Financial Interests, Institutional, Funding: GlaxoSmithKline, Inivata, Merck, Pfizer, Roche; Financial Interests, Personal, Principal Investigator: GlaxoSmithKline, Merck, Pfizer, Roche; Financial Interests, Personal, Advisory Role: AstraZeneca, Dynamo Therapeutics, Exact Sciences, Gilead, GlaxoSmithKline, Merck, Novartis, Pfizer, Puma Biotechnology, Roche. H.S. Rugo: Financial Interests, Institutional, Research Grant: Pfizer, Merck, Novartis, Lilly, Roche, Daiichi, Seattle Genetics, Macrogenics, Sermonix, Boehringer Ingelheim, Polyphor, AstraZeneca, Ayala, Gilead; Financial Interests, Personal, Other, Honoraria: Puma, Mylan, Samsung. S. Im: Financial Interests, Personal, Invited Speaker: Novartis; Non-Financial Interests, Personal, Member of the Board of Directors: Translational Research in Oncology; Financial Interests, Institutional, Research Grant: AstraZeneca, Daewoong, Eisai, Pfizer, Roche; Non-Financial Interests, Personal, Advisory Role: AstraZeneca, Amgen, Daichi Sankyo, Eli Lilly, Eisai, GSK, Hanmi, MSD, Novartis, Pfizer, Roche. M. Md Yusof: Non-Financial Interests, Personal and Institutional, Invited Speaker: Eli Lily, Roche, Novartis, MSD, AstraZeneca, Eisai, MSD, Zuellig Pharma, GSK, Mundi Pharma; Financial Interests, Institutional, Funding: Mundi Pharma; Financial Interests, Institutional, Principal Investigator: MSD, Novartis, Genentech, Astella, AstraZeneca; Non-Financial Interests, Personal and Institutional, Advisory Role: Eli Lily, Roche, Novartis, MSD, AstraZeneca, Eisai, MSD, Zuellig Pharma, GSK, Mundi Pharma; Non-Financial Interests, Personal, Leadership Role: Malaysian Oncological Society. C. Gallardo: Non-Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: MSD, Roche, AstraZeneca, Novartis; Financial Interests, Personal, Advisory Board: MSD, Roche, AstraZeneca, Novartis; Financial Interests, Institutional, Principal Investigator: MSD, BMS, AstraZeneca. C.H. Barrios: Financial Interests, Personal, Invited Speaker: Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi; Financial Interests, Personal, Advisory Board: Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi; Financial Interests, Personal, Stocks/Shares: Biomarker, Tummi, MEDSir; Financial Interests, Institutional, Research Grant: Pfizer, Novartis, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Roche/Genentech, Lilly, Sanofi, Taiho Pharmaceutical, Mylan, Merrimack, Merck, AbbVie, Astellas Pharma, BioMarin, Bristol Myers Squibb, Daiichi Sankyo, Abraxis Biosciences, AB Sc; Financial Interests, Personal, Advisory Role: Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi. J. Perez-Garcia: Financial Interests, Personal, Advisory Board: Roche, Lilly, Daichii Sankyo, AstraZeneca. H. Iwata: Financial Interests, Personal, Advisory Board: Chugai, AstraZeneca, Lilly, Pfizer, Daiichi Sankyo,Kyowa Hakko Kirin, MSD; Financial Interests, Institutional, Funding: Chugai, AstraZeneca, Lilly, Pfizer, Daiichi Sankyo,Kyowa Hakko Kirin, MSD, Sanofi, Novartis, Bayer, Nihon kayaku, Boehringer Ingelheim; Non-Financial Interests, Personal, Principal Investigator: Chugai, AstraZeneca, Lilly, Pfizer, Daiichi Sankyo,Kyowa Hakko Kirin, MSD, Sanofi, Novartis, Bayer, Nihon kayaku, Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Chugai, AstraZeneca, Lilly, Pfizer, Daiichi Sankyo,Kyowa Hakko Kirin, MSD. N. Masuda: Financial Interests, Personal, Speaker’s Bureau: Chugai, AstraZeneca, Pfizer, Eli-Lilly, Eisai; Non-Financial Interests, Personal, Member of the Board of Directors: JBCS (Japanese Breast Cancer Society), JBCRG (Japan Breast Cancer Research Group Association); Financial Interests, Institutional, Research Grant: Chugai, AstraZeneca, Kyowa-Kirin, MSD, Novartis, Pfizer, Eli-Lilly, Eisai, Sanofi, Daiichi Sankyo. E. Gokmen: Financial Interests, Personal and Institutional, Invited Speaker: Roche, Pfizer, BMS, Astellas, AstraZeneca, GEN, Amgen, Novartis; Financial Interests, Personal, Advisory Board: Roche, Pfizer, BMS, AstraZeneca, Novartis, GEN; Financial Interests, Personal, Stocks/Shares: Radius Health, Immunogen, 9 Meters. S. Loi: Non-Financial Interests, Personal, Expert Testimony: Seattle Genetics, Novartis, Bristol Meyers Squibb, Merck, AstraZeneca, Roche-Genentech; Financial Interests, Institutional, Expert Testimony: Aduro Biotech, Novartis, GlaxoSmithKline, Roche-Genentech, AstraZeneca , Silverback Therapeutics, G1 Therapeutics, PUMA Biotechnologies, Pfizer, Gilead Therapeutics, Seattle Genetics, Bristol Meyers Squibb; Financial Interests, Personal, Advisory Board: Akamara Therapeutics; Financial Interests, Institutional, Research Grant: Novartis, Bristol Meyers Squibb, Merck, Puma Biotechnology, Eli Lilly, Nektar Therapeutics AstraZeneca , Roche-Genentech, Seattle Genetics. Z. Guo: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. X. Zhou: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. V. Karantza: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. W. Pan: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer, Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Eisai, Celgene; Financial Interests, Personal, Full or part-time Employment, Spouse: Roche; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche, Medivation. All other authors have declared no conflicts of interest.
LBA17_PR - Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB)
- Gabriel N. Hortobagyi (Houston, TX, United States of America)
Abstract
Background
ML-2 (NCT01958021) is a randomized phase III clinical trial investigating first-line (1L) RIB, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), + letrozole (LET) vs placebo (PBO) + LET in postmenopausal pts with HR+/HER2− ABC. ML-2 previously reported a statistically significant improvement in progression-free survival (PFS; primary endpoint) with RIB + LET vs PBO + LET (HR, 0.56; 95% CI, 0.43-0.72). We report the protocol-specified final analysis of OS (key secondary endpoint).
Methods
Postmenopausal pts with HR+/HER2− ABC were randomized 1:1 to receive RIB + LET or PBO + LET. Pts were excluded if they received a prior CDK4/6i, chemotherapy (CT), or ET in the advanced setting. OS was evaluated with a stratified log-rank test and summarized using Kaplan–Meier methods. This protocol-specified analysis was planned after 400 deaths.
Results
The intention-to-treat population included 668 pts (RIB: 334; PBO: 334). At data cutoff (10 June 2021), 47 pts were still on treatment (RIB: 30 [9.0%]; PBO: 17 [5.1%]) and the median follow-up was 79.7 mo (min, 74.6 mo). Final OS was evaluated after 400 deaths (RIB: 181 [54.2%]; PBO: 219 [65.6%]). RIB + LET showed a significant OS benefit vs PBO + LET (median, 63.9 vs 51.4 mo; HR, 0.76; 95% CI, 0.63-0.93;
Conclusions
To date, this is the first report of a statistically significant and clinically meaningful OS benefit with a 1L CDK4/6i in postmenopausal pts with HR+/HER2– ABC. After a median follow-up of >6.5 y, median OS improvement was >12 mo for 1L RIB + LET vs PBO + LET.
Clinical trial identification
NCT01958021 (CLEE011A2301).
Editorial acknowledgement
This abstract was developed with editorial assistance provided by Casey Nielsen, PhD of MediTech Media, LLC. Editorial support was funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
G.N. Hortobagyi: Financial Interests, Personal, Research Grant, Grant support to institution to conduct trial. Personal fees member/chair Steering Committee: Novartis. S.M. Stemmer: Financial Interests, Institutional, Research Grant: Rabin Medical Center. H.A. Burris III: Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Novartis; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: AstraZeneca; Financial Interests, Institutional, Other, Payment to institution for consulting services performed by Dr. Burris: AstraZeneca; Financial Interests, Institutional, Other, Payment to institution for consulting services performed by Dr. Burris: FORMA Therapeutics; Financial Interests, Institutional, Other, Payment to institution for consulting services performed by Dr. Burris: Celgene; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Incyte; Financial Interests, Institutional, Other, ayment to institution for consulting services performed by Dr. Burris: Incyte; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Roche; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Bristol Myers Squibb; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: MedImmune; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Macrogenics; Financial Interests, Institutional, Other, Payment to institution for expert testimony performed by Dr. Burris: Novartis; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Boehringer Ingelheim; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Lilly; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Seattle Genetics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Merck; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Aglos; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Jounce Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Moderna Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: CytomX Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: GlaxoSmithKline; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Verastem; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Tesaro; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: BioMed Valley Discoveries; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: TG Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Vertex; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: eFFECTOR Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Janssen; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Gilead Sciences; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: BioAtla; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: CicloMed; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Harpoon Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Arch; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Arvinas; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Revolution Medicines; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Array BioPharma; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Bayer; Non-Financial Interests, Personal, Other, Non-compensated consulting services performed by Dr. Burris: Bayer, Pfizer, Novartis; Financial Interests, Institutional, Invited Speaker, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: BIND Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Kyocera; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: miRNA Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Pfizer; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Takeda/Millennium; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Foundation Medicine; Non-Financial Interests, Personal, Other, Uncompensated consulting work: Daiichi Sankyo; Financial Interests, Personal and Institutional, Full or part-time Employment: HCA Healthcare/Sarah Cannon; Financial Interests, Personal and Institutional, Leadership Role: HCA Healthcare/Sarah Cannon; Financial Interests, Personal and Institutional, Stocks/Shares: HCA Healthcare/Sarah Cannon; Non-Financial Interests, Personal, Other, Non-compensated consulting services performed by Dr. Burris: GRAIL. Y.S. Yap: Financial Interests, Personal, Other, not specified: Novartis; Non-Financial Interests, Personal, Other, not specified: Novartis; Financial Interests, Personal, Other, not specified: Pfizer; Non-Financial Interests, Personal, Other, not specified: Pfizer; Financial Interests, Personal, Other, not specified: Lilly; Non-Financial Interests, Personal, Other, not specified: Lilly; Financial Interests, Personal, Other, not specified: AstraZeneca; Non-Financial Interests, Personal, Other, not specified: AstraZeneca; Financial Interests, Personal, Other, not specified: Roche; Non-Financial Interests, Personal, Other, not specified: Roche; Financial Interests, Personal, Other, not specified: Eisai; Non-Financial Interests, Personal, Other, not specified: Eisai; Financial Interests, Personal, Other, not specified: MSD; Financial Interests, Personal, Other, not specified: Inivata. G.S. Sonke: Financial Interests, Institutional, Other, Institutional reimbursement for patient accrual: Novartis; Financial Interests, Institutional, Other, Institutional reimbursement for education and steering committee activities: Novartis; Non-Financial Interests, Institutional, Other, Institutional research support: Merck; Non-Financial Interests, Institutional, Other, Institutional research support: AstraZeneca; Non-Financial Interests, Institutional, Other, Institutional research support: Roche. L. Hart: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Speaker’s Bureau: Novartis. M. Campone: Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Eli Lilly. K. Petrakova: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: BMS. E.P. Winer: Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Tessaro; Financial Interests, Personal, Advisory Board: Leap; Financial Interests, Institutional, Research Grant, Research funding (institution): Merck; Financial Interests, Institutional, Research Grant, Research funding (institution): Genentech. W. Janni: Financial Interests, Personal and Institutional, Research Grant: Novartis. P.F. Conte: Financial Interests, Personal, Writing Engagements: Novartis. D. Cameron: Financial Interests, Institutional, Advisory Board, Institution reimbursed for my time on advisory boards: Novartis; Financial Interests, Institutional, Advisory Board, Institution reimbursed for my time on advisory boards: Pfizer; Financial Interests, Institutional, Other, Institution reimbursed for my time on an IDMC: Lilly. F. André: Financial Interests, Institutional, Funding, Research funding (institution): AstraZeneca; Financial Interests, Institutional, Funding, Research funding (institution): Lilly; Financial Interests, Institutional, Funding, Research funding (institution): Novartis; Financial Interests, Institutional, Funding, Research funding (institution): Pfizer; Financial Interests, Institutional, Funding, Research funding (institution): Roche. C. Arteaga: Financial Interests, Institutional, Research Grant, Research funding: Pfizer; Financial Interests, Institutional, Research Grant, Research funding: Lilly; Financial Interests, Institutional, Research Grant, Research funding: Takeda; Financial Interests, Institutional, Research Grant, Research funding: Radius; Financial Interests, Institutional, Research Grant, Research funding: PUMA Technology; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Symphogen; Financial Interests, Personal, Advisory Board: TAIHO Oncology; Financial Interests, Personal, Advisory Board: PUMA Technology; Financial Interests, Personal, Advisory Board: RADIUS; Financial Interests, Personal, Advisory Board: H3Biomedicine; Financial Interests, Personal, Advisory Board: OrigiMed; Financial Interests, Personal, Advisory Board: Daiichi Sankyo. J.P. Zarate: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. A. Chakravartty: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. T. Taran: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. F. Le Gac: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. P. Serra: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. J. O'Shaughnessy: Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: Novartis; Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: Lilly; Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: Merck; Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: Seattle Genetics.
Invited Discussant LBA16 and LBA17_PR
- Gonzalo Gomez-Abuin (Buenos Aires, Argentina)
Q&A and live discussion
- Gonzalo Gomez-Abuin (Buenos Aires, Argentina)