Background

The anticipated approval of the first specific PIK3CA inhibitor, apelisib, has increased interest in the frequency and range of PIK3CA genomic alterations (GA) in the major subtypes of mBC.

Methods

DNA was extracted from 3,871 mBC: 1,259 ER+/HER2-, 1,969 HER2 amplified (amp) and 643 TNBC. GA, tumor mutational burden (TMB) and microsatellite instability (MSI) were identified by hybrid-capture. PD-L1 was determined by IHC.

Results

PIK3CA GA were significantly higher in ER + (39%) and HER2amp (37%) and lower in TNBC (21%) groups and dominated by point mutations and indels (mut) (Table). The H1047R was the most frequent PIK3CA GA in all groups. ESR1 GA were highest in ER+ and BRCA1 GA were most frequent in PIK3CAmut- TNBC and BRCA2 GA were most frequent in PIK3CAmut- ER+. FGFR1 GA were significantly more frequent in PIK3CAmut- ER+ and EGFR and BRAF GA were most frequent in PIK3CAmut+ TNBC. Biomarkers of potential immunotherapy benefit including CD274amp and PD-L1 expression in immunocytes were most frequent in the TNBC patients, while TMB was highest in the PIK3CAmut+ cohort, regardless of subtype.Table:

306PD

Conclusions

A wide variety of PIK3CA GA are identified in mBC and appear to influence other important biomarkers such as BRCA1/2 GA and TMB status. The PIK3CA GA distribute differently among the ER+, HER2+ and TNBC cohorts and may impact the initial and future use of PIK3CA inhibitors in the treatment of the disease.

Legal entity responsible for the study

Foundation Medicine.

Funding

Foundation Medicine.

Disclosure

E.S. Sokol: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. L.A. Albacker: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J.A. Elvin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J. Vergilio: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J..K. Killian: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. N. Ngo: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. D. Lin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. S. Ramkissoon: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. E. Severson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. S.M. Ali: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. A.B. Schrock: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J. Chung: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. P. Reddy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. V.A. Miller: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. B.M. Alexander: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Foundation Medicine. K. McGregor: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J.S. Ross: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. All other authors have declared no conflicts of interest.

Background

In ER+ HER2- metastatic breast cancer (MBC), resistance to estrogen deprivation by Aromatase Inhibitors (AI) can stem from activating ESR1 mutations (ESR1_mut) or from other less characterized, mutually exclusive mechanisms. In this study, we report on factors associated with the onset of ESR1_mut during therapy (vs other mechanisms of resistance).

Methods

PADA-1 (NCT03079011) is a phase III trial testing the clinical utility of real time ESR1_mut detection (on cell-free DNA, every 2 months) in ER+ HER2- MBC pts treated first line with AI and palbociclib. Main inclusion criteria are pts with no overt resistance to adjuvant AI and no prior therapy for MBC. This analysis compared pts who experienced a progressive disease with no ESR1_mut detected (ESR1_wt-PD) with those with a rising ESR1_mut detected during therapy.

Results

1017 MBC pts were included in PADA-1 from 04/2017 to 01/2019 and are being followed-up. As of 01/31/2019, 242 pts presented either with an ESR1_wt-PD (n = 139, 57.4%) or a detectable ESR1_mut (n = 103, 42.6% (either prior to PD or at time of PD) at any time during AI-palbociclib therapy. During the first 6 months on treatment, ESR1_mut (n = 17, 18.7%) was less frequent than ESR1_wt-PD (n = 74, 81.3%); after 6 months, the opposite was true (ESR1mut: n = 80, 53.0% vs ESR1_wt-PD n = 71, 47.0%); this change was highly significant (Chi2 test, p < 0.001). Based to a Fine-Gray model adjusted for the number of metastases, a higher risk of ESR1_mut during therapy was observed in pts with bone (HR = 2.5 [1.1; 5.6]) or skin (HR = 1.9 [1.1; 3.7]) metastases while liver metastases were associated with a lower risk of ESR1_mut (HR = 0.5 [0.3; 0.8]). No other characteristic (including exposure to AI in the adjuvant setting) was associated with the onset of ESR1_mut.

Conclusions

ctDNA analysis in PADA-1 suggests that ESR1_mut are rarely involved in primary resistance to AI-palbociclib therapy (i.e. PD within 6 months) but may represent the most prevalent mechanism of acquired resistance. The observed association between ESR1_mut and metastatic sites might underlie the reported higher efficacy of selective estrogen receptor degraders (such as fulvestrant) in pts with bone metastases.

Clinical trial identification

NCT: 03079011; EudraCT: 2016-004360-18.

Legal entity responsible for the study

UNICANCER.

Funding

Pfizer.

Disclosure

F. Bidard: Advisory / Consultancy, lectures fees: Pfizer; Advisory / Consultancy, lectures fees: AstraZeneca. B. Pistilli: Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self), Advisory / Consultancy: Pfizer; Advisory / Consultancy: Puma; Advisory / Consultancy: Merus. T. de La Motte Rouge: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Eisai; Advisory / Consultancy: MSD. R. Sabatier: Licensing / Royalties: Novartis; Research grant / Funding (self), Travel / Accommodation / Expenses, Licensing / Royalties: AstraZeneca; Licensing / Royalties: Tesaro; Research grant / Funding (institution): EISAI; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. F. Clatot: Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS. T. Bachelot: Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self), Research grant / Funding (institution), Non-remunerated activity/ies: Novartis; Honoraria (self), Research grant / Funding (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Research grant / Funding (institution), Non-remunerated activity/ies: Pfizer. S. Delaloge: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Puma; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.

Background

Recently, palbociclib plus exemestane with GnRH agonist demonstrated a statistically significant improvement in progression-free survival (PFS) compared with that of the capecitabine for premenopausal women with hormone receptor-positive metastatic breast cancer (median PFS 20·1 vs. 14·4 months, p = 0·0235 ; HR 0·659 [95% C.I. 0·437–0·994])(Park YH et al, J Clin Oncol 37, 2019 [suppl; abstr 1007]). We evaluated PROs in YoungPEARL phase ll trial.

Methods

Pts (N = 189) were randomized 1:1 to receive palbociclib plus exemestane with GnRH agonist or capecitabine. PROs were assessed at day 1 (baseline), every 6 weeks, and at the end of treatment, using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-30). Repeated-measures mixed-effect analyses were carried out to compare on-treatment overall scores and changes from baseline between the treatment groups while controlling for baseline.

Results

Questionnaire completion rates were 100% at baseline and during treatment from baseline to 84 weeks in each group. Global health status/QoL scores were maintained from baseline to the end of treatment across all time points within each cohort. Between-treatment comparison in the change from baseline functioning scale scores showed trends favoring palbociclib arm for physical functioning (0.12 vs -3.66, p = 0.1201) while favoring capecitabine arm for emotional (0.87 vs 2.61, p = 0.5963) and social functioning (2.63 vs 5.97, p = 0.3234). There was a trend to improve appetite loss (-5.27 vs 0.72, p = 0.1484) and insomnia tended to get worse (3.81 vs -2.65, p = 0.0736) in palbociclib arm while capecitabine arm showed the greater improvement in pain (-2.80 vs -5.83, p = 0.3200) but worsening in diarrhea (1.17 vs 7.37, p = 0.0598) without statistical significance.

Conclusions

These findings show that palbociclib plus endocrine therapy maintained high PRO scores with some different function and symptom profiles compared with capecitabine arm.

Clinical trial identification

NCT02592746.

Legal entity responsible for the study

Korea Cancer Study Group.

Funding

Pfizer.

Disclosure

All authors have declared no conflicts of interest.

Background

RIB plus an NSAI is indicated for premenopausal pts with hormone-receptor–positive (HR+), HER2− ABC based on data from the ML-7 trial (NCT02278120), including progression-free survival (PFS), which was longer with RIB vs PBO (median 23.8 vs 13.0 months; HR 0.55; P < 0.0001). It is important to understand how PFS data translate to pt benefit in terms of OS and QoL. Maintenance of functioning, work productivity and activity, and pain reduction have been reported for the overall population. We present updated OS and QoL data (cutoff: 30 November 2018) for pts who received an NSAI.

Methods

Pre/perimenopausal pts with HR+/HER2− ABC, ≤ 1 line of prior chemotherapy, and no prior endocrine therapy for ABC were randomized 1:1 to receive RIB or PBO plus goserelin with either an NSAI (letrozole or anastrozole) or tamoxifen. The primary endpoint was PFS. OS, the key secondary endpoint, was evaluated by stratified log-rank test in the overall population and summarized using Kaplan-Meier methods. Time to 10% deterioration (TTD) was estimated using the EORTC QLQ-C30 patient questionnaire and a stratified log-rank test.

Results

The NSAI cohort included 248 pts in the RIB arm and 247 in the PBO arm. As of the data cutoff, 37.1% of patients in the RIB arm and 18.6% of pts in the PBO arm remained on treatment. Of the pts who discontinued study treatment, 69.2% in the RIB arm and 73.1% in the PBO arm started subsequent therapy. Median OS was not reached in the RIB arm vs 40.7 months in the PBO arm (hazard ratio, 0.699 [95% CI, 0.501-0.976]), and the benefit of adding RIB was generally consistent across pt subgroups within this cohort. Median TTD in global QoL was 34.2 months in the RIB arm vs 23.3 months in the PBO arm (hazard ratio, 0.69 [95% CI, 0.52-0.91]). Analyses of key QoL domains will be presented at the meeting. Updated analyses of adverse events revealed no unexpected safety signals.

Conclusions

RIB plus an NSAI prolonged OS and improved QoL vs PBO plus an NSAI in premenopausal pts with HR+, HER2– ABC. Additional follow-up did not reveal any new safety signals in this subgroup.

Clinical trial identification

NCT02278120.

Editorial acknowledgement

John McGuire, PhD, of MediTech Media, LLC funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

Y. Lu: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Clinical trial study fee, grant, advisory board, speaker: Novartis; Advisory / Consultancy, Consultation fee: Pfizer; Advisory / Consultancy: Boehringer Ingelheim; Research grant / Funding (self): Roche; Research grant / Funding (self): Merck Sharp & Dohme; Research grant / Funding (self): Pfizer; Research grant / Funding (self): GlaxoSmithKline. A. Bardia: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Radius Health; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Immunomedics; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): Innocrin; Advisory / Consultancy: Biothernostics Inc.; Advisory / Consultancy, Travel / Accommodation / Expenses: Spectrum Pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: Taiho; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy: Daiichi Pharma. R.V. Vázquez: Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche. M.A. Colleoni: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Pfizer; Honoraria (self): Novartis; Advisory / Consultancy: OBI Pharma; Advisory / Consultancy: Puma Biotechnology; Advisory / Consultancy: Celldex. D. Tripathy: Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Pfizer. B.R. Lanoue: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. D. Chandiwana: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. A. Ridolfi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. G. Hughes: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. J.P. Zarate: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. I. Gounaris: Non-remunerated activity/ies: PharmaMar; Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. N. Harbeck: Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer. All other authors have declared no conflicts of interest.

Background

The introduction of trastuzumab in combination with chemotherapy has significantly improved clinical outcomes for patients with HER2-positive breast cancer. HLX02 was developed as a trastuzumab biosimilar with the potential to increase market competition and treatment accessibility in China and around the world.

Methods

We conducted a randomised, double-blind, parallel-controlled equivalence study (HLX02-BC01) at 89 study centres in China, Philippines, Poland and Ukraine. Eligible women were aged 18 years or older, had histologically confirmed HER2+ breast cancer, an Eastern Cooperative Oncology Group performance status of 0 to 1, and estimated life expectancy ≥3 months. Patients were randomised at 1:1 to receive an intravenous dose of 8 mg/kg of HLX02 or EU-trastuzumab with docetaxel on Day 1 -Cycle 1 followed by a dose of 6 mg/kg once every 3 weeks in 3-weekly cycles for up to a maximum of 12 months. The primary endpoint was best overall response rate at Week 24 (ORR_wk24) evaluated by blinded central imaging review. Secondary endpoints included clinical benefit rate (CBR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS), safety outcomes with immunogenicity and incidence of adverse events up to 12 months.

Results

Of 1046 patients enrolled, 649 were randomly allocated to receive HLX02 (n = 324) or EU-trastuzumab (n = 325). The ORR was 71.0% (230 of 324 patients; 95% CI: 66.0, 75.9) for HLX02 and 71.4% (232 of 325 patients; 95% CI: 66.5, 76.3) for EU-trastuzumab. The p-value at 95% CI (p = 0.952) was completely contained within the pre-defined equivalence boundaries of ± 13.5%. The difference in ORR between the 2 treatments was 0.4 (95% CI: -7.4, 6.6). Safety outcomes and immunogenicity were similar between the treatment groups at Week 24.

Conclusions

Among women with HER2+ metastatic breast cancer, the use of HLX02 compared with EU-trastuzumab resulted in an equivalent ORR at Week 24. All secondary efficacy and safety analyses at Week 24 also supported the conclusion of therapeutic equivalence; HLX02 does not demonstrate new safety signals in comparison with EU-trastuzumab. Further study results at Month 12 will be reported in August once the study is unblinded.

Clinical trial identification

NCT03084237; EudraCT: 2016-000206-10.

Legal entity responsible for the study

Shanghai Henlius Biotech, Inc.

Funding

Shanghai Henlius Biotech, Inc.

Disclosure

B. Xu: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. Q. Zhang: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. T. Sun: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. W. Li: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. Y. Teng: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. X. Hu: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. I. Bondarenko: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. H. Adamchuk: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. L. Zhang: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. D. Trukhin: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. B. Li: Full / Part-time employment: Shanghai Henlius Biotech,Inc. B. Shan: Full / Part-time employment: Shanghai Henlius Biotech,Inc. J. Cheng: Full / Part-time employment: Shanghai Henlius Biotech,Inc. T. Peng: Full / Part-time employment: Shanghai Henlius Biotech,Inc. W. Jiang: Full / Part-time employment: Shanghai Henlius Biotech,Inc. S. Liu: Full / Part-time employment: Shanghai Henlius Biotech,Inc. X. Zhang: Full / Part-time employment: Shanghai Henlius Biotech,Inc. Q. Wang: Full / Part-time employment: Shanghai Henlius Biotech, Inc. E. Liu: Full / Part-time employment: Henlix Biotech, Inc. A.Y. Luk: Full / Part-time employment: Shanghai Henlius Biotech,Inc.

Background

The MF07-01 trial is a multicenter randomized study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone in de novo stage IV breast cancer (BC) patients. The aim of this study is to evaluate the importance of LRT in patients who lived at least 5 years after the diagnosis of de novo Stage IV BC.

Methods

At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. Continuous and categorical variable differences between LRT and ST groups were analyzed using t-test and Chi-square test, respectively. Overall survival (OS) and 5-year survival rates were compared using Kaplan-Meier log-rank tests. Univariate and multivariate Cox models were used to estimate hazard ratios.

Results

During 124 months of follow-up, 26% of patients in LRT group and 11% of patients in ST group remained alive. Median survival was 46 months for LRT (n = 134) and 35.5 months for ST (n = 132) [HR:0.65, 95%CI;0.49-0.85, p = 0.002]. Solitary bone metastasis patients’ median survival was 14.5 months longer in the LRT group compared with the ST group [HR:0.53, 95%CI; 0.29-0.98, p = 0.04]; 22% of solitary bone metastasis patients in the LRT group and 5% in the ST group were alive. Regarding the patients who lived at least 5 years since randomization, LRT (p = 0.004), hormone receptor positivity (p = 0.007), hormonotherapy (p = 0.0001), bisphosphonates usage (p = 0.02), T2 tumor (p = 0.0008) and 2 or more organ metastases (p = 0.007) were associated with OS in univariate analysis, and in a multivariate Cox proportional model with a significant baseline and clinical characteristics, LRT [OR = 1.75, p = 0.05)], bisphosphonates usage [OR = 1.93, p = 0.05), T2 tumor [OR = 3.5, p = 0.003), and 2 or more organ metastases [OR = 0.48, p = 0.03] were found to be significantly related with OS.

Conclusions

In the current analysis, patients at the diagnosis of de novo stage IV BC who underwent LRT followed by ST had a 75% higher chance to live at least 5 years compared with the patients who received only ST. Longer follow-up of the study discloses that LRT should be presented to the patient when discussing treatment options.

Clinical trial identification

NCT00557986.

Legal entity responsible for the study

Turkish Federation of Breast Diseases Societies.

Funding

Turkish Federation of Breast Diseases Societies.

Disclosure

All authors have declared no conflicts of interest.

Background

Premenopausal women with MBC have a distinct tumor biology, and more aggressive behavior. In the BOLERO-2 trial, adding EVE to exemestane (EXE) significantly prolonged progression-free survival (PFS) compared with EXE alone in postmenopausal women with recurrent/metastatic HR+, HER2– breast cancer. LEO is the first randomized phase II trial investigating the effect of adding EVE to LET in ovarian suppressed premenopausal women with MBC.

Methods

Patients (pts) with progression or prior exposed to tamoxifen with or without GnRH agonist, either sequentially or concurrently, in adjuvant or metastatic setting were randomly assigned (2:1) to receive LEUP+LET+EVE (arm A) or LEUP+LET (arm B) until disease progression or unacceptable toxicity. Randomization was stratified by the presence of visceral metastases and sensitivity to endocrine therapy. The primary end point was PFS. Secondary end points included overall survival (OS), objective response rate (ORR), and safety.

Results

Between January 2014 and October 2018, 137 pts were enrolled in this study. Baseline characteristics were well balanced between the two groups. The median age was 44 years (range 24-54), 74.5% had endocrine-sensitive disease, and 60.6% had visceral metastasis. At a median follow-up of 32.4 months, the median PFS was 18.1 months in arm A and 13.8 months in arm B, respectively (HR 0.73; 95% CI, 0.48 to 1.11; P = 0.137), and predominant in pts with visceral metastases (16.4 vs. 9.5 Mo) (HR 0.58; 95% CI, 0.34 to 0.99; p = 0.048). The median OS was not reached in both arms. ORR was 46.9% and 28.2% in arms A and B, respectively (P = 0.051). The most common grade 3/4 adverse events were neutropenia (9.8% in arm A vs. 0% in arm B), AST elevation (5.4% vs. 0%), enterocolitis (4.3% vs. 0%), and anemia (3.3% vs. 0%), without grade 3/4 stomatitis in both arms. Five pts discontinued treatment (1 AKI, 1 pneumonitis, 1 liver dysfunction, 2 unknown) but no treatment related death.

Conclusions

Adding EVE to LET demonstrated numerically improved PFS (D 4.3 Mo, median PFS), higher ORR. Significant improved PFS was noted in patients with visceral metastases.

Clinical trial identification

NCT02344550.

Legal entity responsible for the study

Sung-Bae Kim.

Funding

Novartis, Dongkook Pharma Co. Ltd.

Disclosure

All authors have declared no conflicts of interest.

Background

Abemaciclib is an oral, selective CDK4 & 6 inhibitor dosed on a continuous schedule and approved in combination with endocrine therapy (ET) for HR+/HER2- ABC patients (pts) outside of China in more than 50 countries.

MONARCHplus evaluated the efficacy and safety of abemaciclib plus ET in predominantly Chinese pts with HR+/HER2- ABC.

Methods

MONARCHplus was a randomized-controlled, double-blind phase III trial for postmenopausal women with endocrine sensitive (Cohort A) or endocrine resistant (Cohort B) HR+/HER2- ABC. In Cohort A, pts received abemaciclib (150 mg Q12h)/ placebo (P) + NSAI (anatrozole or letrozole) as first-line ET. In Cohort B, pts received abemaciclib/P + F following progression to ET. Both cohorts were randomized at a 2:1 ratio. The primary objective was PFS in Cohort A with a key secondary objective of PFS in Cohort B. The trial was powered for Cohort A to 80% at 1-sided α=.025 assuming a hazard ratio (HR) of 0.626 in favor of abemaciclib + NSAI, with analyses at 119 and 170 PFS events.

Results

At the pre-specified interim, 119 PFS events were observed in Cohort A (n = 306) and 82 events in Cohort B (n = 157). Abemaciclib +NSAI and abemaciclib + F statistically and significantly improved PFS and ORR (see Table). PFS benefit was consistent within all stratification factors and pre-specified sensitivity analyses. The safety profile for both abemaciclib arms was consistent with previous reports for abemaciclib plus ET and included neutropenia, diarrhea, leukopenia, and anemia as the most frequent adverse events (AEs).Table: LBA25

Summary of PFS and ORR in ITT population

Conclusions

Abemaciclib in combination with NSAI or fulvestrant provided a statistically significant and clinically meaningful improvement in PFS in predominantly Chinese postmenopausal women with HR+/HER2- ABC with no new safety signals observed. The MONARCHplus interim analysis demonstrated benefit consistent with the MONARCH 2 and 3 studies.

Clinical trial identification

NCT02763566.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

All authors have declared no conflicts of interest.