First new drug in years reduces recurrence in high risk HR+ early breast cancer

Lugano, Switzerland, 20 September 2020 - Adding abemaciclib to hormonal therapy reduces the risk of cancer recurrence by 25% in patients with high-risk early hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer, according to results from a study at ESMO 2020. (1)

"This is the first time in more than 20 years that we have seen an advance in the adjuvant treatment of this form of breast cancer," said lead author Prof Stephen Johnston, from the Royal Marsden Hospital NHS Foundation Trust, London, UK. He explained that hormone receptor positive breast cancer is the commonest form of breast cancer, affecting 70% of patients, with most being diagnosed with early disease.

"Many of these patients can be cured with currently available treatments: surgery, radiotherapy, chemotherapy and hormone treatment. But about 20% have high-risk disease and will develop a recurrence either locally in the breast or elsewhere in the body over the first ten years of treatment," he explained.

"These patients with high-risk early breast cancer show a degree of resistance to hormone therapy, relapsing early despite everything we currently give them," said Johnston. "CDK4/6 inhibitors, such as abemaciclib, have transformed the way we treat metastatic breast cancer over the last few years, overcoming primary endocrine resistance and improving survival. So it was an obvious step to see whether adding abemaciclib to hormone treatment in patients with high-risk early breast cancer could reduce the risk of their cancer returning."

The international phase 3 monarchE study included 5637 patients with HR+ HER2- early breast cancer with clinical and/or pathological risk factors putting them at high risk for relapse. After completing their primary treatment they were randomised on an open-label basis to abemaciclib (150mg twice daily for two years) plus endocrine therapy or endocrine therapy alone.

"We found a 25% reduction in recurrence of cancer with the first two years when abemaciclib was added to hormone therapy compared to hormone therapy alone," reported Johnston. During this time 11.3% of patients in the control group had a relapse of their cancer compared to 7.8% of those in the abemaciclib group, an absolute difference of 3.5% which translates to a 25.3% reduction in risk. Most of the reductions occured in sites of distant metastases, especially to liver and bone.

"This is the first study to show that adding a CDK4/6 inhibitor to endocrine therapy significantly improves invasive disease free survival in the adjuvant setting," said Giuseppe Curigliano, Associate Professor of Medical Oncology at the University of Milan, Italy, and Chair of the ESMO Guidelines Committee.

"This is a very important trial and the findings will change practice. Once approved for high risk HR+ HER2- early breast cancer the new standard of care for these patients will be to add two years of abemaciclib to endocrine therapy," he suggested.

Curigliano suggested it would have been interesting to have included genetic signature into the assessment of patients at high risk, in addition to number of positive lymph nodes, tumour size, histologic grade and Ki-67 (a marker of proliferation). Johnston said that tissue and plasma samples had been collected from all of the study participants for translational research that will include looking at genomic signatures and response to abemaciclib.

"The safety data are important, particularly the number of patients treated with abemaciclib who had to discontinue or required dose reductions due to side-effects," said Curigliano. A total of 463 (16.6%) of patients discontinued abemaciclib due to adverse events, most commonly diarrhea; 306 of these continued on endocrine therapy. The protocol allowed dose reduction from 150 to 100mg twice daily if required. He noted: "Adherence to treatment will be an important issue to be considered in the real life population of patients when this treatment is approved and used in clinical practice."

Curigliano added, "For the future it will be important to understand if we can potentially spare chemotherapy in this group of patients treated with a CDK4/6 inhibitor. This would need to be investigated in a randomised clinical trial."

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Notes to Editors

Please make sure to use the official name of the meeting in your reports: ESMO Virtual Congress 2020
Official Congress Hashtag: #ESMO20

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References

(1) Abstract LBA5_PR 'Abemaciclib in high risk early breast cancer' will be presented by Stephen Johnston in the Presidential Symposium II on Sunday, 20 September 2020, 18:30 - 20:25 CEST. Annals of Oncology, Volume 31 Supplement 4, September 2020.

The study will be published simultaneously in the Journal of Clinical Oncology, 'Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high risk, early breast cancer (monarchE)', DOI: 10.1200/JCO.20.02514, https://ascopubs.org/doi/full/10.1200/JCO.20.02514

About the European Society for Medical Oncology (ESMO)

ESMO is the leading professional organisation for medical oncology. With more than 25,000 members representing oncology professionals from over 160 countries worldwide, ESMO is the society of reference for oncology education and information. ESMO is committed to offer the best care to people with cancer, through fostering integrated cancer care, supporting oncologists in their professional development, and advocating for sustainable cancer care worldwide. http://www.esmo.org

LBA5_PR - Abemaciclib in high risk early breast cancer

S.R.D. Johnston1, N. Harbeck2, R. Hegg3, M. Toi4, M. Martin5, Z. Shao6, M. Campone7, E.P. Hamilton8, J. Sohn9, V. Guarneri10, J. Cortes11, P. Neven12, F. Boyle13, I. Smith14, D. Headley15, R. Wei15, M. Frenzel15, J. Cox16, J. O'Shaughnessy17, P. Rastogi18

1Breast Cancer Medicine, Royal Marsden Hospital NHS Foundation Trust, London, UK, 2Breast Center, Dept OB&GYN, LMU University Hospital, Munich, Germany, 3Gynecology and Obstetrics, Gynecological Clinical Service School of Medicine, Univ. Sao Paulo, Sao Paulo, SP, Brazil, 4Breast Unit, Kyoto University-Graduate school of medicine, Kyoto, Japan, 5Servicio de Oncologia Médica Department, Hospital General Universitario Gregorio Maranon, Universidad Complutense, Ciberonc GEICAM, Madrid, Spain, 6Breast Surgery, Fudan University Shanghai Cancer Center, Shanghi, China, 7MEDICAL ONCOLOGY, ICO Institut de Cancerologie de l'Ouest René Gauducheau, Saint-Herblain, CEDEX, France, 8Director, Breast and Gynecologic Research Program, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, USA, 9Division of Medical Oncology, Yonsei Cancer Center, Seoul, Korea, Republic of, 10Department of Surgery, Oncology and Gastroenterology Instituto Oncologico Veneto IRCCS, University of Padova, Padova, Italy, 11Head, Breast Cancer Program, IOB Institute of Oncology, Quiron Group, Barcelona, Spain, 12Department of Gynaecological Oncology / Multidisciplinary Breast Center, University Hospitals Leuven - Campus Gasthuisberg, Leuven, Belgium, 13Patricia Ritchie Centre for Cancer Care and Research, Mater Hospital, North Sydney, North Sydney, Australia, 14Chief Medical Officer, Artios Pharma Ltd, Cambridge, UK, 15Oncology, Eli Lilly and Company, Indianapolis, IN, USA, 16Oncology, Eli Lilly and Company, Windlesham, IN, UK, 17Breast Cancer Prevention and Treatment, Texas Oncology - Baylor Sammons Cancer Center, Dallas, TX, USA, 18Oncology, NSABP Foundation, Pittsburgh, USA

Background: Over 90% of patients with breast cancer are diagnosed with early breast cancer (EBC). While many patients with HR+ disease will not recur or have distant relapse with standard therapies, up to 30% of patients whose cancer has high risk clinical and/or pathological features may experience distant relapse, many in the first 2 years. Novel treatment options are needed to prevent early recurrences and development of metastases for these patients. Abemaciclib is an oral, continuously dosed CDK4 & 6 inhibitor approved for use in HR+, HER2- advanced breast cancer (ABC). Efficacy and safety of abemaciclib in ABC supported phase 3 evaluation in the adjuvant setting.

Methods: monarchE, an open-label, phase 3 study, included patients with HR+, HER2-, high risk EBC, who completed primary treatment. Patients with greater-than or equal to 4 positive nodes, or 1-3 nodes and at least one of the following: tumor size greater-than or equal to 5 cm, histologic grade 3, or central Ki-67 greater-than or equal to 20%, were eligible, and randomized (1:1) to abemaciclib (150 mg BID for 2 years) plus endocrine therapy (ET) or ET alone. A prespecified interim analysis was planned at ~293 IDFS events. The primary endpoint was invasive disease-free survival (IDFS) per STEEP criteria. Secondary endpoints included distant relapse-free survival (DRFS), overall survival, and safety.

Results: 5,637 patients were randomized. With 323 IDFS events observed in the intent-to-treat population, positive efficacy required a 2-sided p-value 0.0264. Abemaciclib plus ET demonstrated a statistically significant improvement in IDFS versus ET alone (p=.0096, HR: 0.747, 95% CI: 0.598, 0.932), corresponding to a 25.3% reduction in the risk of an IDFS event. The 2-year IDFS rates were 92.2% vs 88.7%, respectively. A similar improvement was observed for DRFS (HR: 0.717, 95% CI: 0.559, 0.920) with 2-year DRFS rates of 93.6% and 90.3%, respectively. Consistent benefit was seen in all prespecified subgroups. The most frequent AEs were diarrhea, neutropenia and fatigue in the abemaciclib arm and arthralgia, hot flush and fatigue in the control arm. Safety was consistent with the known profile of abemaciclib.

Conclusions: Abemaciclib when combined with ET is the first CDK4 & 6 inhibitor to demonstrate a statistically significant improvement in IDFS in patients with HR+, HER2-, high risk EBC.

Clinical trial identification: NCT03155997

Editorial acknowledgement: Writing assistance provided by Sarah C. Nabinger (Eli Lilly and Company)

Legal entity responsible for the study: Eli Lilly and Company

Funding: Eli Lilly and Company

Disclosure: S.R.D. Johnston: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Eli Lilly and Company; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Research grant/Funding (self): Puma Biotechnology; Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche/Genentech. N. Harbeck: Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer. M. Toi: Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Takeda; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Kyowa-Hakko-Kirin; Honoraria (self), Research grant/Funding (institution): Taiho; Research grant/Funding (institution), Officer/Board of Directors: JBCRG Association; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Daiichi-Sankyo; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Eli Lilly and Company; Honoraria (self): MSD; Honoraria (self): Genomic Health; Honoraria (self): Novartis; Honoraria (self), Honorarium for advisory meeting: Konica Minolta; Research grant/Funding (institution): Astellas; Honoraria (self), Honorarium for advisory meeting: BMS; Honoraria (self), Research grant/Funding (institution): Shimadzu; Honoraria (self): Yakult; Honoraria (self), Research grant/Funding (institution): Nippon Kayaku; Research grant/Funding (institution): AFI Technologies; Advisory/Consultancy: Athenex Oncology; Officer/Board of Directors: Organization for Oncology and Translational Research ; Officer/Board of Directors: Kyoto Breast Cancer Research Network. M. Martin: Honoraria (self), Research grant/Funding (self), personal fees: Roche; Honoraria (self), Research grant/Funding (self), personal fees: Novartis; Honoraria (self), Research grant/Funding (self), personal fees: Puma; Honoraria (self), Travel/Accommodation/Expenses, personal fees: Eli Lilly and Company; Honoraria (self), personal fees: GSK; Honoraria (self), personal fees: AstraZeneca; Honoraria (self), personal fees: Amgen; Honoraria (self), personal fees: Taiho Oncology; Honoraria (self), personal fees: Pharmamar; Honoraria (self), personal fees: Pfizer; Honoraria (self), personal fees: Daiichi Sanyo. M. Campone: Advisory/Consultancy, fees to the institution: AstraZeneca; Advisory/Consultancy, fees to the institution: Sanofi; Advisory/Consultancy, fees to the institution: Servier; Advisory/Consultancy, fees to the institution: AbbVie; Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy, fees to the institution: Accord; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, fees to the institution: Pfizer; Advisory/Consultancy: GT1. E.P. Hamilton: Advisory/Consultancy, Research grant/Funding (institution), advisory board (no personal compensation accepted): Eli Lilly and Company; Advisory/Consultancy, Research grant/Funding (institution), advisory board (no personal compensation accepted): Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (institution), speaker's bureau (no personal compensation accepted): Genentech/Roche; Advisory/Consultancy: Flatiorn Health; Advisory/Consultancy, Research grant/Funding (institution), consulting (no personal compensation accepted): Cascadian Therapeutics; Research grant/Funding (institution): Hutchinson MediPharma; Research grant/Funding (institution): OncoMed; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): StemCentrx; Research grant/Funding (institution): Abbvie; Research grant/Funding (institution): Curis; Research grant/Funding (institution): Verastem; Research grant/Funding (institution): Zymeworks; Research grant/Funding (institution): Syndax; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Rgenix; Advisory/Consultancy, Research grant/Funding (institution), consulting (no personal compensation accepted): Novartis; Advisory/Consultancy, Research grant/Funding (institution), consulting (no personal compensation accepted): Mersana; Research grant/Funding (institution): Taplmmune; Research grant/Funding (institution): BerGenBio; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Kadmon; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): H3 Biomedicine; Research grant/Funding (institution): Radius Health; Research grant/Funding (institution): Acerta; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): FujiFilm; Research grant/Funding (institution): Effector; Research grant/Funding (institution): Syros; Research grant/Funding (institution): Unum; Research grant/Funding (institution): Sutro; Research grant/Funding (institution): Aravive; Research grant/Funding (institution): Deciphera; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Sermonix; Research grant/Funding (institution): Zenith; Research grant/Funding (institution): Arvinas; Research grant/Funding (institution): ArQule; Research grant/Funding (institution): Torque; Research grant/Funding (institution): Harpoon; Research grant/Funding (institution): Fachon; Research grant/Funding (institution): Orinove; Research grant/Funding (institution): Molecular Template; Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution), consulting (no personal compensation accepted): Daiichi; Advisory/Consultancy, Research grant/Funding (institution), consulting (no personal compensation accepted): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), consulting (no personal compensation accepted): Silverback Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), consulting (no personal compensation accepted): Black Diamond.

J. Sohn: Research grant/Funding (institution): MSD; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Eli Lilly and Company; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): GSK; Research grant/Funding (institution): CONTESSA; Research grant/Funding (institution): Daiichi Sankyo. V. Guarneri: Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly and Compnay; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Roche. J. Cortes: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy: Cellestia; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Biothera Pharmaceutical; Advisory/Consultancy: Merus; Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Erytech; Advisory/Consultancy: Athenex; Advisory/Consultancy: Polyphor; Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp&Dohme; Advisory/Consultancy: GSK; Advisory/Consultancy: Leuko; Advisory/Consultancy: Bioasis; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Samsung Bioepis; Research grant/Funding (institution): Ariad Pharmaceuticals; Research grant/Funding (institution): Baxalta GMBH/Servier Affaires; Research grant/Funding (institution): Bayer Healthcare; Research grant/Funding (institution): F. Hoffman-La Roche; Research grant/Funding (institution): Guardanth Health; Research grant/Funding (institution): Piqur Therapeutics; Shareholder/Stockholder/Stock options: MedSIR; Research grant/Funding (institution): Puma C; Research grant/Funding (institution): Queen Mary University of London . P. Neven: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly and Company.F. Boyle: Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Novartis. I. Smith: Full/Part-time employment, Former employee of Eli Lilly and Company: Eli Lilly and Compnay. D. Headley: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company; Shareholder/Stockholder/Stock options: Novartis; Shareholder/Stockholder/Stock options: Takeda; Shareholder/Stockholder/Stock options: Varian Medical Systems; Shareholder/Stockholder/Stock options: Utah Medical Products; Shareholder/Stockholder/Stock options: Zoetis; Shareholder/Stockholder/Stock options: Bayer; Shareholder/Stockholder/Stock options: Merck; Shareholder/Stockholder/Stock options: Roche; Shareholder/Stockholder/Stock options: Evgen; Shareholder/Stockholder/Stock options: AstraZeneca; Shareholder/Stockholder/Stock options: Johnson & Johnson; Shareholder/Stockholder/Stock options: Pfizer; Shareholder/Stockholder/Stock options: Varex Imaging; Shareholder/Stockholder/Stock options: Zimmer BioMet; Shareholder/Stockholder/Stock options: Chugai Pharma. R. Wei: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company. M. Frenzel: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company. J. Cox: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company. J. O'Shaughnessy: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Agendia; Advisory/Consultancy: Amgen Biotechnology; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Britol-Myers Squibb; Advisory/Consultancy: Celgene; Advisory/Consultancy: Eisai; Advisory/Consultancy: Genentech; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: GRAIL; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Heron Therapeutics; Advisory/Consultancy: Ipsen Biopharmaceuticals; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Merck; Advisory/Consultancy: Myriad; Advisory/Consultancy: Novartis; Advisory/Consultancy: Ondonate Therapeutics; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Puma Biotechnology; Advisory/Consultancy: Prime Oncology; Advisory/Consultancy: Roche; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Syndax Pharmaceuticals; Advisory/Consultancy: Takeda. P. Rastogi: Travel/Accommodation/Expenses: Eli Lilly and Company; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Roche/Genentech.

All other authors have declared no conflicts of interest.