Abstract 355P
Background
Optimal sequence of endocrine therapy (ET) for ER+/HER2- advanced breast cancer (ABC) after progression on CDK4/6 inhibitors (CDK4/6i) remains uncertain. We aimed to compare the effectiveness and safety of everolimus-based ET (EVE) with ET alone (ETa) in this setting.
Methods
Multicentre, international, retrospective, quasi-experimental study of female patients (pts) with ER+/HER2- ABC who started next line of therapy after progression on CDK4/6i until 31/12/2022 with EVE (EVE-cohort, 9 sites) or ETa in sites where EVE is not standard of care in this setting (ETa-cohort, 5 sites), in Belgium and Portugal. We excluded pts receiving alpelisib as immediate next line. Primary endpoint was real-world progression-free survival (rwPFS); secondary endpoints were time to EVE failure, time to chemotherapy, overall survival (OS) and safety. We compared baseline characteristics and assessed their prognostic/predictive value in univariate/sub-group analyses. Time-to-event endpoints were assessed from start of EVE/ETa and measures of association were determined with 95% confidence interval (CI).
Results
We included 207 pts (EVE-cohort: 150; ETa-cohort: 57). Baseline characteristics were well balanced, except for visceral disease and number of prior lines (Table). ET was mostly exemestane in EVE-cohort (77%) and fulvestrant in ETa-cohort (61%). Median rwPFS was 5.0 for EVE vs. 4.3 m for ETa (HR 0.75, 95%CI 0.55-1.02), with a numerically higher magnitude of benefit in pts with PIK3CA-AKT1-PTEN pathway alterations (HR 0.56, 0.20-1.61, N=20 EVE: 15, ETa: 5). Secondary efficacy endpoints in the table. Multivariate analysis will be presented at the meeting. No notable safety issues emerged. Table: 355P
Main baseline characteristics and secondary time-to-event endpoints
| EVE (N=150) | ETa (N=57) | p-value | |
| Characteristics | |||
| Age, median (IQR) | 61.0 (53.0, 71.0) | 63.0 (50.0, 72.0) | 0.61 |
| ECOG, 0-1 (%) | 132 (88) | 53 (93) | 0.68 |
| Charlson Comorbidity Index, 6 (%) | 116 (77) | 43 (75) | 0.63 |
| PR-positive (%) | 107 (71) | 36 (63) | 0.26 |
| Recurrent (%) | 108 (72) | 38 (68) | 0.45 |
| Visceral (%) | 97 (65) | 43 (75) | 0.02 |
| One prior line (%) | 86 (57) | 45 (79) | ConclusionsWe found a non-statistically significant trend for superiority of EVE compared to ETa for unadjusted rwPFS. Pts with PIK3CA-AKT-PTEN pathway alterations, may particularly benefit from the combination. Clinical trial identificationEditorial acknowledgementLegal entity responsible for the studyInstitut Jules Bordet. FundingThe study received financial support from Novartis for study set up and data collection from patients treated at Institut Jules Bordet. DisclosureD. Martins Branco: Financial Interests, Personal, Invited Speaker, (03/02/2022 and 23/09/2022): AstraZeneca/DaiichiSankyo; Financial Interests, Personal, Full or part-time Employment: European Society for Medical Oncology; Financial Interests, Institutional, Funding, Institutional funding for observational research projects - role: medical research fellow at Institut Jules Bordet (01/01/2021 - 31/08/2023): Novartis; Financial Interests, Institutional, Funding, Institutional funding for an investigator-initiated clinical trial (NCT05075538) - role: medical research fellow at Institut Jules Bordet (01/01/2021 - 31/08/2023): F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Other, Two industry-sponsored clinical trials (NCT01358877 and NCT03498716) - role: academic partner medical advisor at Institut Jules Bordet (01/01/2021 - 31/08/2023): F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Funding, Institutional funding for an investigator-initiated clinical trial (NCT03339843) - role: medical research fellow at Institut Jules Bordet (01/01/2021 - 31/08/2023): Eli Lilly; Non-Financial Interests, Member of Board of Directors: Associação de Investigação e Cuidados de Suporte em Oncologia - Portuguese MASCC affiliate; Non-Financial Interests, Leadership Role, Portuguese Young Oncologists Committee Chair: November 2020 - May 2022: Sociedade Portuguesa de Oncologia. P.G. Aftimos: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure, Servier, G1 Therapeutics, Radius, Deloitte, Menarini, Gilead, Novartis, Eisai, Lilly; Financial Interests, Personal, Invited Speaker: Synthon, Amgen; Financial Interests, Institutional, Research Grant: Roche. B.A. Pereira: Financial Interests, Personal, Invited Speaker: GSK. A.L.V. Matos: Financial Interests, Personal, Invited Speaker: Astrazeneca, Roche, Lilly; Financial Interests, Personal, Advisory Board: Novartis, Grunenthal. L.M. Raposo Fernandes: Financial Interests, Personal, Advisory Board: Novartis, Pfizer; Financial Interests, Personal, Other, Consultancy: Astrazeneca, Pfizer. G. Nader Marta: Other, Meeting/travel grants to attend medical conference.: AstraZeneca. F.P. Duhoux: Financial Interests, Institutional, Advisory Board: Roche, Pfizer, AstraZeneca, Lilly, Novartis, Amgen, Daiichi Sankyo, Pierre Fabre, Gilead, Seagen, MSD, Seagen, Novartis, MSD; Financial Interests, Institutional, Invited Speaker: Novartis, Pfizer, MSD, Roche; Financial Interests, Institutional, Local PI: MSD, Boehringer Ingelheim, Pfizer, Novartis, Lilly, Abbvie, Seagen, Gilead, AstraZeneca, Menarini, Immutep. A.R. Meira Garcia: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo/AstraZeneca; Financial Interests, Personal and Institutional, Local PI: Leopharma. C. Santos: Financial Interests, Personal, Invited Speaker, Speaker: Pfizer; Non-Financial Interests, Principal Investigator, Clinical trial: Msd. E. de Azambuja: Financial Interests, Personal, Advisory Board: Roche/GNE, Novartis, Seagen, MSD; Financial Interests, Personal, Invited Speaker: Zodiac, Libbs, Pierre Fabre, Lilly, AstraZeneca, Gilead Sciences; Financial Interests, Personal, Other, Chair of the Gilead Sciences Research Scholars Program in Solid Tumours: Gilead Sciences; Financial Interests, Institutional, Research Grant: Roche/GNE, AstraZeneca, GSK/Novartis, Servier; Financial Interests, Institutional, Other, Travel Grant: Roche/GNE; Financial Interests, Institutional, Local PI: MSD, ABCSG, Nektar, Gilead, Immunomedics, Synthon, Odonate Therapeutics; Financial Interests, Steering Committee Member, ASCENT 04: Gilead; Financial Interests, Steering Committee Member, Aphinity, Lorelei, Impassion03: Roche; Financial Interests, Steering Committee Member, AURORA: Breast International Group; Financial Interests, Steering Committee Member, Olympia: AstraZeneca; Financial Interests, Personal, Other, Travel grant: AstraZeneca; Non-Financial Interests, Advisory Role, Member of the cardio-oncology council: European Society of Cardiology (ESC); Non-Financial Interests, Advisory Role, Belgium governmental institution for cancer: KCE; Non-Financial Interests, Other, Editorial board member: ESMO Open; Non-Financial Interests, Advisory Role: Anticancer Fund; Non-Financial Interests, Leadership Role, President 2023-2026: Belgian Society of Medical Oncology (BSMO). All other authors have declared no conflicts of interest. Resources from the same session364P - Elacestrant in combination with abemaciclib in patients (pts) with brain metastasis (mets) from estrogen receptor-positive (ER+), HER2-negative (HER2-) breast cancer: Preliminary data from ELECTRA, an open-label, multicenter, phase Ib/II studyPresenter: Eva Ciruelos Session: Poster session 14 365P - Interim analysis (IA) of the giredestrant (G) + samuraciclib (SAMURA) arm in MORPHEUS breast cancer (BC): A phase I/II study of G treatment (tx) combinations in patients (pts) with oestrogen receptor-positive (ER+), HER2-negative, locally advanced/metastatic BC (LA/mBC)Presenter: Mafalda Oliveira Session: Poster session 14 366P - Exploring the benefit of combining paclitaxel with capivasertib treatment in PI3K/AKT/PTEN-altered and non-altered TNBC preclinical modelsPresenter: Cath Eberlein Session: Poster session 14 367P - Phase I/II dose escalation study evaluating first-in-class eIF4A inhibitor zotatifin in ER+ metastatic breast cancerPresenter: Ezra Rosen Session: Poster session 14 368P - Tucidinostat and metronomic capecitabine plus endocrine therapy for patients with HR+/HER2- advanced breast cancer after CDK4/6 inhibitors: Preliminary findings of a multi-center, phase II studyPresenter: Qiufan Zheng Session: Poster session 14 370P - A phase Ib study to evaluate the efficacy and safety of afuresertib plus fulvestrant in subjects with locally advanced or metastatic HR+/HER2- breast cancer who failed standard of care therapies: A subgroup analysis of efficacy in PIK3CA/AKT1/PTEN-altered subjectsPresenter: Pin Zhang Session: Poster session 14 371P - Efficacy of metronomic capecitabine plus aromatase inhibitor as initial therapy in patients with hormone receptor-positive, HER2-negative metastatic breast cancer: The phase III MECCA trialPresenter: Shusen Wang Session: Poster session 14 This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
|