Background

KAITLIN (NCT01966471) compared adjuvant AC-KP versus AC-THP in patients with HER2-positive, high-risk EBC. A preplanned exploratory analysis assessed the relationship between invasive disease-free survival (IDFS) and biomarkers (BMs) potentially related to response.

Methods

Baseline tumor samples were used for central assessment of HER2 and pre-specified BMs including HER2 mRNA expression and PTEN IHC expression by median (med) cutoff, and activating PIK3CA hotspot mutations. The effect of treatment and BMs on IDFS was assessed via descriptive analyses.

Results

BMs were well balanced between treatment arms. No BM subgroup showed more benefit from AC-KP than AC-THP. A trend for reduced benefit with AC-KP vs AC-THP was seen in the HER2 <30% expression and 4 to <6 gene copy number subgroups (Table). No clear prognostic relationships were identified in pooled arms (PIK3CA mut vs non-mut HR=1.27 [0.92–1.74]; HER2 IHC3+ vs IHC2+ HR=0.82 [0.55–1.23]; HER2 mRNA ≥ vs < med HR=0.76 [0.56–1.03]). Table: 42O

Conclusions

Consistent with the primary study results, AC-KP did not reduce the risk of an IDFS event compared to AC-THP in any BM subgroup. HP + chemotherapy remains the standard of care for those with high-risk HER2-positive EBC. No BMs had prognostic value in the pooled arm analyses.

Clinical trial identification

NCT01966471.

Editorial acknowledgement

Support for third-party writing assistance was provided by Tracy McNally, PhD and Holly Strausbaugh, PhD (Twist Medical, Burlingame, CA, USA), funded by F. Hoffmann-La Roche.

Legal entity responsible for the study

F. Hoffmann-La Roche.

Funding

F. Hoffmann-La Roche.

Disclosure

O. Metzger: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AbbVie; Advisory/Consultancy, Research grant/Funding (institution): G1 Therapeutics; Research grant/Funding (institution): Roche; Research grant/Funding (institution), Non-remunerated activity/ies, Co-chair Advisory Board: Pfizer. C. Lambertini: Full/Part-time employment: F. Hoffmann - La Roche Ltd. I.E. Krop: Honoraria (self), Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Pfizer; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Daiichi Sankyo; Honoraria (self): Macrogenics; Honoraria (self): Seattle Genetics; Honoraria (self): Celltrion; Honoraria (self): Merck; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Context Therapeutics. G. Lewis Phillips: Full/Part-time employment: Genentech, Inc; Shareholder/Stockholder/Stock options: F. Hoffmann - La Roche Ltd. C.M. Perou: Advisory/Consultancy, Leadership role, Shareholder/Stockholder/Stock options, Licensing/Royalties: Bioclassifier LLC; Advisory/Consultancy, Shareholder/Stockholder/Stock options, Licensing/Royalties, Officer/Board of Directors: GeneCentric Therapeutics. F. Symmans: Shareholder/Stockholder/Stock options, Licensing/Royalties, Founder shares, licensed intellectual property: Delphi Diagnostics; Shareholder/Stockholder/Stock options: IONIS Pharmaceuticals; Shareholder/Stockholder/Stock options: Eiger Pharmaceuticals. I. Melero: Honoraria (self), Research grant/Funding (institution): Roche/Genentech; Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Alligator Bioscience; Honoraria (self): Bayer; Honoraria (self): Tusk Therapeutics; Honoraria (self): Gossamer Bio; Honoraria (self): Amunix; Honoraria (self): Replimune; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Medincell; Honoraria (self): Monopteros Therapeutics; Honoraria (self): Molecular Partners; Honoraria (self): Biontech; Honoraria (self): PharmaMar. N. Harbeck: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche. E.P. Winer: Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy: Carrick Therapeutics; Honoraria (self), Advisory/Consultancy: G1 Therapeutics; Honoraria (self), Research grant/Funding (institution): Genentech/Roche; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: GSK; Honoraria (self), Advisory/Consultancy: Jounce; Honoraria (self), Advisory/Consultancy: Leap; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy: Syros; Honoraria (self), Advisory/Consultancy: Zymeworks. S-A. Im: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Hanmi; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Non-remunerated activity/ies, Investigational agent for trial: Dae Woong. C.H. Barrios: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Mylan; Research grant/Funding (institution): Merrimack; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Bayer; Research grant/Funding (institution): Astellas Pharma; Honoraria (self), Advisory/Consultancy: Eisai; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Abraxis Biosciences, BioMarin, LEO Pharma, AbbVie, Merck, and Millennium; Research grant/Funding (institution): AB Science, Asana Biosciences, Medivation, Exelixis, and Imclone Systems. H. Bonnefoi: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Non-remunerated activity/ies: Daiichi. J.R. Gralow: Honoraria (self): Genentech/Roche; Honoraria (self): Pfizer; Honoraria (self): Puma; Honoraria (self): AstraZeneca; Honoraria (self): Immunomedics; Honoraria (self): Genomic Health; Honoraria (self): Novartis; Honoraria (self): Sandoz/Hexal; Honoraria (self): Radius; Honoraria (self): Inbiomotion. L. Gianni: Advisory/Consultancy: Hexal Sandoz; Advisory/Consultancy: Seattle Genomics; Advisory/Consultancy: Synthon; Honoraria (self), Advisory/Consultancy: Zymeworks; Advisory/Consultancy: Sanofi-Aventis; Advisory/Consultancy: Forty Seven (CD47); Advisory/Consultancy: Genenta; Advisory/Consultancy: METIS Precision Medicine; Advisory/Consultancy: Novartis; Advisory/Consultancy: Odonate Therapeutics; Honoraria (self), Advisory/Consultancy: Revolution Medicine; Advisory/Consultancy: Synaffix; Advisory/Consultancy: Menarini Ricerche; Advisory/Consultancy: Amgen; Advisory/Consultancy: Biomedical Insights Inc.; Honoraria (self): Daiichi Sankyo; Licensing/Royalties, Co-inventor of European Patent Application N. 12195182.6 and 12196177.5 titled \"PDL-1 expression in anti-HER2 therapy\": Roche. M. Toi: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Chugai, Takeda, Pfizer, Taiho, Eisai, AstraZeneca, Shimadzo, Yakult, Nippon Kayaku; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Kyowa-Kirin, Daiichi Sankyo; Research grant/Funding (institution): Astellas, AFI Technologies, JBCRG Association, Astehnologies, Luxonos, Shionogi, GL Science; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Honoraria (self), Speaker Bureau/Expert testimony: MSD, Exact Science, Novartis; Honoraria (self), Advisory/Consultancy: Konica Minolta, BMS; Advisory/Consultancy: Athenex Oncology, Bertis, Terumo, Kansai Medical Net. S.M. Swain: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, support for third party medical writing: Roche/Genentech; Honoraria (self), Advisory/Consultancy: Exact Sciences (Genomic Health); Honoraria (self), Advisory/Consultancy: Molecular Templates; Honoraria (self), Advisory/Consultancy: Silverback Therapeutics; Honoraria (self), Advisory/Consultancy: Tocagen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eli Lilly; Honoraria (self), Advisory/Consultancy: Natera; Honoraria (self), Advisory/Consultancy: Athenex; Honoraria (self), Advisory/Consultancy: Bejing Medical Foundation; Research grant/Funding (institution): Kailos Genetics; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: Caris Life Sciences; Advisory/Consultancy, Scientific Advisory Board: Inivata. T. Boulet: Full/Part-time employment, Employee from Parexel International GmbH contracted by Roche for Statistical services: F. Hoffmann-La Roche Ltd. C. Song: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche/Genentech. S. de Haas: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche Ltd. All other authors have declared no conflicts of interest.

Background

Venous thromboembolic events (VTE), elevated aminotransferases (EAT) and interstitial lung disease (ILD) are adverse events (AEs) for abemaciclib (oral CDK4 & 6 inhibitor). In monarchE, patients (pts) receiving abemaciclib+endocrine therapy (ET) as adjuvant treatment (txt) of HR+, HER2- high-risk early breast cancer (EBC) reported these AEs more frequently vs ET alone pts.

Methods

The safety population (pop) comprised 5591 treated (tx) pts (median duration of abemaciclib: 17 months). The protocol included management guidance for AEs. Pts with history of VTE were not eligible. Risk factors for VTE (Khorana risk score) and adjuvant radiotherapy (95.4% pts) were well balanced across arms.

Results

In abemaciclib tx pts: Most VTEs were G≥3 (1.3%), primarily pulmonary embolism (0.9%) (Table). Of pts experiencing VTE, 94% received anti-coagulants and 19.4% discontinued abemaciclib or all txt due to VTE. VTEs were increased with tamoxifen txt; G≥3 VTEs were higher in pts with body mass index (BMI)> 25 (1.8%) vs BMI<25 (0.6%). 85% of G≥3 EAT were single occurrences; incidence was highest early on txt (∼3 months). Of pts experiencing G≥3 EAT, 71% had dose hold/reduction and 16% discontinued due to EAT. All G≥3 alanine aminotransferase (ALT) increases, per central lab, were reversible with dose modification or discontinuation. No pts had drug-induced liver injury (no Hy’s law cases). Most ILD events were G1 (1.4%). Of pts experiencing ILD, 52% were tx with steroids/antibiotics and 23% discontinued abemaciclib or all txt due to ILD. ILD was higher in Asians (6.6%; G1: 4.9%; G≥3: 0.3%; 13% of Asian pts with ILD discontinued (0.9% of pop)). Table: 44O

Characteristics of VTEs, EAT and ILD

Conclusions

VTE, EAT and ILD were manageable with dose adjustments and comedications in pts with EBC; results were consistent with the known safety profile of abemaciclib. Although ILD was higher in Asian pop, G≥3 AEs and discontinuations were similar. Most pts experiencing these AEs could continue abemaciclib.

Clinical trial identification

NCT03155997.

Editorial acknowledgement

Eglantine Julle-Daniere.

Legal entity responsible for the study

Eli Lilly.

Funding

Eli Lilly.

Disclosure

M. Toi: Honoraria (self), Research grant/Funding (self), Research grant, Lecture honoraria: Chugai, Takeda, Pfizer, Taiho, Eisai, AstraZeneca, Shimadzu, Yakult; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant, Lecture honoraria, Advisory role for a drug development: Kyowa-Kirin, Daiichi Sankyo; Research grant/Funding (self): JBCRG association, Astellas; Advisory/Consultancy, Research grant/Funding (self): Eli Lilly; Honoraria (self), Lecture Honoraria: MSD, Exact Science, Novartis; Honoraria (self), Advisory/Consultancy, Honoraria for an advisory meeting: Konica Minolta, BMS; Honoraria (self), Research grant/Funding (self), Research Fund and Honoraria for lecture: Nippon Kayaku; Research grant/Funding (self): AFI Technologies; Advisory/Consultancy: Athenex Oncology, Bertis, Terumo, Kansai Medical Net; Advisory/Consultancy, Research grant/Funding (self): Luxonus; Research grant/Funding (self): Shionogi, GL Science; Officer/Board of Directors: JBCRG association, Organisation for Oncology and Translational Research, Kyoto Breast Cancer Research Network. N. Harbeck: Shareholder/Stockholder/Stock options: West German Study Group; Honoraria (self): Roche, Novartis, Amgen, Pfizer, Genomic Health, AstraZeneca, Zodiac Pharma, Pierre Fabre; Advisory/Consultancy: Roche/Genentech, Novartis, Celgene, Pfizer, Eli Lilly, Sandoz, Daiichi Sankyo, Agendia, AstraZeneca, Merck Sharp & Dohme, Odonate Therapeutics, Seattle Genetics, West German Study Group, Pierre Fabre; Research grant/Funding (institution): Roche/Genentech (Inst), Novartis (Inst), Pfizer (Inst), Lilly (Inst), Merck Sharp & Dohme (Inst). J.M. Puig: Honoraria (self), Personal fees: Protocol JPCF. J. Cruz: Honoraria (self), Advisory/Consultancy, Lectures, Travel, Advisory: PharmaMar, Roche, Novartis, Pfizer; Honoraria (self), Advisory/Consultancy, Lectures, Advisory: Eli Lilly, AstraZeneca; Advisory/Consultancy: Daiichi, Seagen, Glaxo; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Lectures: Bayer. M. Takahashi: Honoraria (self): Eli Lilly; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self), Research grant/Funding (self): Eisai; Research grant/Funding (self): Kyowa Kirin; Research grant/Funding (self): Taiho. M. Hulstijn, E.A. Twum, A. Regev, B. San Antonio: Full/Part-time employment: Eli Lilly. D.M. Median: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Institutional research funding, Honoraria, Lecture fee, Consulting/Advisory role: Eli Lilly; Advisory/Consultancy, Non-remunerated activity/ies, Educational, Lecture fee, Consulting/Advisory role: AstraZeneca; Research grant/Funding (self), Lecture fee: A&D Pharma; Honoraria (self): Clovis; Advisory/Consultancy, Travel/Accommodation/Expenses: Genekor; Honoraria (self), Advisory/Consultancy, Lecture fee, Honoraria, Advisory role: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses, Lecture fee, Advisory, Travel, Educational: Pfizer; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses, Lecture fee, Honoraria, Travel, Educational: Roche; Honoraria (self): Samsung Bioepis. M. Campone: Honoraria (institution), Advisory/Consultancy, Consulting/advisory/fees to the Institution: AstraZeneca, Sanofi, Servier, AbbVie, Accord, Pfizer, Seagen; Advisory/Consultancy: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: GT1. All other authors have declared no conflicts of interest.

Background

Venous thromboembolic events (VTE), elevated aminotransferases (EAT) and interstitial lung disease (ILD) are adverse events (AEs) for abemaciclib (oral CDK4 & 6 inhibitor). In monarchE, patients (pts) receiving abemaciclib+endocrine therapy (ET) as adjuvant treatment (txt) of HR+, HER2- high-risk early breast cancer (EBC) reported these AEs more frequently vs ET alone pts.

Methods

The safety population (pop) comprised 5591 treated (tx) pts (median duration of abemaciclib: 17 months). The protocol included management guidance for AEs. Pts with history of VTE were not eligible. Risk factors for VTE (Khorana risk score) and adjuvant radiotherapy (95.4% pts) were well balanced across arms.

Results

In abemaciclib tx pts: Most VTEs were G≥3 (1.3%), primarily pulmonary embolism (0.9%) (Table). Of pts experiencing VTE, 94% received anti-coagulants and 19.4% discontinued abemaciclib or all txt due to VTE. VTEs were increased with tamoxifen txt; G≥3 VTEs were higher in pts with body mass index (BMI)> 25 (1.8%) vs BMI<25 (0.6%). 85% of G≥3 EAT were single occurrences; incidence was highest early on txt (∼3 months). Of pts experiencing G≥3 EAT, 71% had dose hold/reduction and 16% discontinued due to EAT. All G≥3 alanine aminotransferase (ALT) increases, per central lab, were reversible with dose modification or discontinuation. No pts had drug-induced liver injury (no Hy’s law cases). Most ILD events were G1 (1.4%). Of pts experiencing ILD, 52% were tx with steroids/antibiotics and 23% discontinued abemaciclib or all txt due to ILD. ILD was higher in Asians (6.6%; G1: 4.9%; G≥3: 0.3%; 13% of Asian pts with ILD discontinued (0.9% of pop)). Table: 44O

Characteristics of VTEs, EAT and ILD

Conclusions

VTE, EAT and ILD were manageable with dose adjustments and comedications in pts with EBC; results were consistent with the known safety profile of abemaciclib. Although ILD was higher in Asian pop, G≥3 AEs and discontinuations were similar. Most pts experiencing these AEs could continue abemaciclib.

Clinical trial identification

NCT03155997.

Editorial acknowledgement

Eglantine Julle-Daniere.

Legal entity responsible for the study

Eli Lilly.

Funding

Eli Lilly.

Disclosure

M. Toi: Honoraria (self), Research grant/Funding (self), Research grant, Lecture honoraria: Chugai, Takeda, Pfizer, Taiho, Eisai, AstraZeneca, Shimadzu, Yakult; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant, Lecture honoraria, Advisory role for a drug development: Kyowa-Kirin, Daiichi Sankyo; Research grant/Funding (self): JBCRG association, Astellas; Advisory/Consultancy, Research grant/Funding (self): Eli Lilly; Honoraria (self), Lecture Honoraria: MSD, Exact Science, Novartis; Honoraria (self), Advisory/Consultancy, Honoraria for an advisory meeting: Konica Minolta, BMS; Honoraria (self), Research grant/Funding (self), Research Fund and Honoraria for lecture: Nippon Kayaku; Research grant/Funding (self): AFI Technologies; Advisory/Consultancy: Athenex Oncology, Bertis, Terumo, Kansai Medical Net; Advisory/Consultancy, Research grant/Funding (self): Luxonus; Research grant/Funding (self): Shionogi, GL Science; Officer/Board of Directors: JBCRG association, Organisation for Oncology and Translational Research, Kyoto Breast Cancer Research Network. N. Harbeck: Shareholder/Stockholder/Stock options: West German Study Group; Honoraria (self): Roche, Novartis, Amgen, Pfizer, Genomic Health, AstraZeneca, Zodiac Pharma, Pierre Fabre; Advisory/Consultancy: Roche/Genentech, Novartis, Celgene, Pfizer, Eli Lilly, Sandoz, Daiichi Sankyo, Agendia, AstraZeneca, Merck Sharp & Dohme, Odonate Therapeutics, Seattle Genetics, West German Study Group, Pierre Fabre; Research grant/Funding (institution): Roche/Genentech (Inst), Novartis (Inst), Pfizer (Inst), Lilly (Inst), Merck Sharp & Dohme (Inst). J.M. Puig: Honoraria (self), Personal fees: Protocol JPCF. J. Cruz: Honoraria (self), Advisory/Consultancy, Lectures, Travel, Advisory: PharmaMar, Roche, Novartis, Pfizer; Honoraria (self), Advisory/Consultancy, Lectures, Advisory: Eli Lilly, AstraZeneca; Advisory/Consultancy: Daiichi, Seagen, Glaxo; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Lectures: Bayer. M. Takahashi: Honoraria (self): Eli Lilly; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self), Research grant/Funding (self): Eisai; Research grant/Funding (self): Kyowa Kirin; Research grant/Funding (self): Taiho. M. Hulstijn, E.A. Twum, A. Regev, B. San Antonio: Full/Part-time employment: Eli Lilly. D.M. Median: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Institutional research funding, Honoraria, Lecture fee, Consulting/Advisory role: Eli Lilly; Advisory/Consultancy, Non-remunerated activity/ies, Educational, Lecture fee, Consulting/Advisory role: AstraZeneca; Research grant/Funding (self), Lecture fee: A&D Pharma; Honoraria (self): Clovis; Advisory/Consultancy, Travel/Accommodation/Expenses: Genekor; Honoraria (self), Advisory/Consultancy, Lecture fee, Honoraria, Advisory role: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses, Lecture fee, Advisory, Travel, Educational: Pfizer; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses, Lecture fee, Honoraria, Travel, Educational: Roche; Honoraria (self): Samsung Bioepis. M. Campone: Honoraria (institution), Advisory/Consultancy, Consulting/advisory/fees to the Institution: AstraZeneca, Sanofi, Servier, AbbVie, Accord, Pfizer, Seagen; Advisory/Consultancy: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: GT1. All other authors have declared no conflicts of interest.

Background

monarchE demonstrated that adjuvant abemaciclib (oral CDK4 & 6 inhibitor)+endocrine therapy (ET) significantly improves invasive disease-free survival (IDFS) in HR+, HER2- high-risk early breast cancer (EBC) compared to ET alone. Here, we report the primary outcome (PO) efficacy and safety data in patients (pts) located in Asia (mainland China, Hong Kong, Japan, Korea, Singapore, and Taiwan), comprising 1,155 (20.5%) of the 5,637 pts of the intent-to-treat (ITT) population.

Methods

Pts with HR+, HER2-, high risk EBC were randomized 1:1 to abemaciclib+ET or ET alone and stratified by prior treatment (txt), menopausal status, and region (North America/Europe; Asia; Other). Exploratory analyses were conducted among pts enrolled from Asia, (median follow-up: ∼19 months in both arms).

Results

In total, 75 IDFS events were observed in pts from Asia (33 in abemaciclib+ET; 42 in ET alone). Abemaciclib+ET demonstrated numerical benefit in IDFS, reflecting a 22.3% reduction in the risk of developing invasive disease [HR (95% CI) = 0.777 (0.493, 1.227)]. Two-year IDFS rates were 93.2% in abemaciclib+ET and 90.1% in ET alone. There was also a numerical improvement in distant relapse free survival (DRFS) [HR (95% CI) = 0.758 (0.455, 1.264)], with 2-year DRFS rates of 94.4% vs 91.7%. The median txt duration of abemaciclib was 17.7 months. In the abemaciclib arm, the most frequent adverse event (AE) was diarrhea (89.5%), most were G1/2 (55.8%/28.7%). More G≥3 AEs and serious AEs were observed with abemaciclib+ET vs ET (53.5% vs 10.5% and 12.1% vs 6.3%), with neutropenia (31.5%) being the most frequent G≥3 AE. Interstitial lung disease occurred in 6.6% pts, G≥3 in 0.3% pts. G≥3 ALT and AST increases occurred in 4.2% and 3.1% pts, respectively.14.5% of abemaciclib-treated pts discontinued abemaciclib or all txt due to AEs.

Conclusions

In pts from Asia with HR+, HER2-, high-risk EBC, abemaciclib plus standard adjuvant ET led to a clinically meaningful improvement in IDFS and DRFS, consistent with benefits demonstrated in the ITT population. Safety was consistent with the known safety profile of abemaciclib. Abemaciclib is the first CDK4 & 6 inhibitor to demonstrate effective and tolerable txt in pts with high-risk EBC, including pts from Asia.

Clinical trial identification

NCT03155997.

Editorial acknowledgement

Eglantine Julle-Daniere.

Legal entity responsible for the study

Eli Lilly.

Funding

Eli Lilly.

Disclosure

Y-S. Yap: Advisory/Consultancy, Personal fees/non-financial support: Eli Lilly; Advisory/Consultancy, Personal fees/non-financial support: Novartis; Advisory/Consultancy, Personal fees/non-financial support: Pfizer; Advisory/Consultancy, Personal fees/non-financial support: AstraZeneca; Advisory/Consultancy, Personal fees/non-financial support: Eisai; Advisory/Consultancy, Personal fees/non-financial support: Roche; Advisory/Consultancy, Personal fees/non-financial support: MSD; Advisory/Consultancy, Personal fees: Inivata. S-B. Kim: Research grant/Funding (self): Novartis; Research grant/Funding (self): Sanofi-Aventis; Research grant/Funding (self): DongKook Pharm Co. Y. Sagara: Honoraria (self), Personal fees: Eli Lilly; Honoraria (self), Personal fees: Pfizer; Honoraria (self), Personal fees: AstraZeneca. S. Sherwood: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly. R.E. McNaughton: Full/Part-time employment: Eli Lilly. R.J. Wei: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly. M. Toi: Honoraria (self), Research grant/Funding (self): Chugai, Takeda, Pfizer, Taiho, Eisai, AstraZeneca, Eli Lilly, Shimadzu, Yakult; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Kyowa-Kirin; Research grant/Funding (self): JBCRG association; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Daiichi Sankyo; Honoraria (self): MSD; Honoraria (self): Exact Science; Honoraria (self): Novartis; Honoraria (self), Advisory/Consultancy, Honoraria for an advisory meeting: Konica Minolta; Research grant/Funding (self): Astellas; Honoraria (self), Advisory/Consultancy, Honoraria for an advisory meeting: BMS; Honoraria (self), Research grant/Funding (self), Research Fund and Honoraria for lecture: Nippon Kayaku; Research grant/Funding (self): AFI technologies; Advisory/Consultancy: Athenex Oncology, Bertis, Terumo, Kansai Medical Net; Advisory/Consultancy, Research grant/Funding (self): Luxonus; Research grant/Funding (self): Shionogi; Research grant/Funding (self): GL Science; Officer/Board of Directors, Board of directors: JBCRG association, Organisation for Oncology and Translational Research, Kyoto Breast Cancer Research Network. All other authors have declared no conflicts of interest.