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 session353P - Clinical outcomes of treatment with CDK4/6 inhibitors in metastatic breast cancer among carriers of germline pathogenic variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2Presenter: Robert Scheel Session: Poster session 14 354P - Synergistic preclinical efficacy through combination of the CDK4 and CDK2 selective inhibitors, PF-07220060 and PF-07104091, respectively, in HR+ HER2- breast cancerPresenter: Lars Anders Session: Poster session 14 356P - Real-world effectiveness in subgroups of palbociclib + endocrine therapy in HR+/HER2- ABC patients: Interim results of the PERFORM studyPresenter: Georg Pfeiler Session: Poster session 14 358P - Everolimus or ribociclib in patients with HER2-negative, hormone-receptor positive metastatic breast cancer and circulating tumor cells: Results from DETECT IVaPresenter: Tanja Fehm Session: Poster session 14 359P - Overall survival of palbociclib (PAL) + endocrine therapy (ET) in Japanese patients with hormone receptor-positive (HR+)/ human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) in the 1st line (1L) or 2nd line (2L) setting: A multicenter observational studyPresenter: Takahiro Nakayama Session: Poster session 14 360P - Identification of circulating immune factors as predictive biomarkers of CDK4/6i treatment efficacy in advanced breast cancerPresenter: Sara Cabrero-de las Heras Session: Poster session 14 361P - PALVEN: A phase Ib study of palbociclib, letrozole and venetoclax in ER and BCL2-positive metastatic breast cancerPresenter: Christine Muttiah Session: Poster session 14 362P - Dose reductions due to treatment-related side effects and survival outcomes in breast cancer patients treated with CDK4/6 InhibitorsPresenter: Pinar Kubilay Tolunay Session: Poster session 14 363P - Palbociclib exposure in relation to response and toxicity in patients with advanced breast cancerPresenter: Sanne Buijs Session: Poster session 14 This site uses cookies. 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