Abstract 204P
Background
First-line (1L) anti-HER2 therapy has dramatically improved survival for patients (pts) with HER2+ metastatic breast cancer (MBC). We investigated clinicopathologic predictors of never progressive disease (PD) in the multicenter, real-world ESME-MBC cohort (NCT03275311).
Methods
We selected women with HER2+ MBC diagnosed between 2008 and 2021 and treated with 1L anti-HER2-based therapy who had not experienced PD within 36 months (mo) of MBC diagnosis and with ≥60 mo of follow-up (fu). We used a multivariable logistic regression model with backward selection and bootstrap cross-validation to identify clinicopathologic characteristics of pts who never had PD at the last fu (still in 1L).
Results
Among 4, 697 pts with HER2+ MBC, 1, 083 had not experienced progression at 36 mo, of whom 318 were excluded due to fu <60mo, yielding a final study population of 765 pts. Of them, 523 (68.3%) never developed PD during fu (median fu of 97.9 mo (95%CI 94.8-101.9). Median progression-free survival (PFS) was 106.4mo (95%CI 92.8-130.8), and 60mo PFS was 68.4% (IC95% 65.1-71.7). Hormone receptor negative (HR-) status, use of 1L chemotherapy (CT) + dual HER2 inhibition, and absence of visceral metastases at diagnosis were independently associated with never PD at last fu (Odds Ratio (OR) 1.74 (1.23 – 2.48), 1.51 (1.07 – 2.14), 0.51 (0.24 – 1.12), respectively Table). The model's predictive performance had an AUC of 0.64. Table: 204P
Multivariable predictors of never PD
| N | OR [95%CI] | P | ||
| Tumor grade | I/II | 393 | 1 | 0.004 |
| III | 281 | 1.48 [1.05 ; 2.09] | ||
| Undeterminate | 48 | 2.90 [1.37 ; 6.91] | ||
| Age at MBC | <55 yrs | 363 | 1 | 0.022 |
| ≥55 yrs | 359 | 0.68 [0.49 ; 0.95] | ||
| First-line regimen | CT + H | 285 | 1 | 0.045 |
| CT+HP | 368 | 1.51 [1.07 ; 2.14] | ||
| Other | 69 | 0.98 [0.56 ; 1.73] | ||
| HR | HR+ | 453 | 1 | 0.002 |
| HR- | 269 | 1.74 [1.23 ; 2.48] | ||
| Metastases site at diagnosis | Non-visceral | 331 | 1 | 0.037 |
| Visceral non CNS | 358 | 0.68 [0.48 ; 0.95] | ||
| CNS | 33 | 0.51 [0.24 ; 1.12] |
H: Trastuzumab, P: Pertuzumab
Conclusions
In this large cohort, pts who had at least 3 years of disease control under 1L anti-HER2 therapy had 68.4% odds of remaining progression-free 2 years later. Negative hormone receptor status was the main driver of this long-term control. This may support de-escalation strategies in HER2+ patients with long-standing response to therapy. However, effective biomarkers to predict never PD beyond clinicopathologic features are warranted.
Clinical trial identification
NCT03275311.
Editorial acknowledgement
Data provided by 18 French Comprehensive Cancer Centers (FCCC) and project management and support by ESME. 18 Participating FCCC: I. Curie, Paris/Saint-Cloud, G. Roussy, Villejuif, I. Cancérologie de l′Ouest, Angers/ Nantes, C. F. Baclesse, Caen, ICM Montpellier, C. L. Bérard, Lyon, C. G-F Leclerc, Dijon, C. H. Becquerel, Rouen; I. C. Regaud, Toulouse; C. A. Lacassagne, Nice; Institut de Cancérologie de Lorraine, Nancy; C. E. Marquis, Rennes; I. Paoli-Calmettes, Marseille; C. J. Perrin, Clermont Ferrand; I. Bergonié, Bordeaux; C. P. Strauss, Strasbourg; I. J. Godinot, Reims; C. O.Lambret, Lille.
Legal entity responsible for the study
Unicancer.
Funding
The ESME MBC database receives financial support from an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai and Daiichi Sankyo). Data collection, analysis, and publication are managed entirely by Unicancer independently of the industrial consortium.
Disclosure
T. Grinda: Financial Interests, Personal, Invited Speaker: Cancérologie Pratique, Gilead, Pfizer. A. Mailliez: Financial Interests, Institutional, Invited Speaker: AstraZeneca, MSD, Novartis, Roche; Financial Interests, Personal, Invited Speaker: Pierre Fabre, OSEUS, Seagen, Pfizer, Daiichi Sankyo; Financial Interests, Personal, Expert Testimony: GSK. T. Bachelot: Financial Interests, Personal, Advisory Board: Roche, Novartis, AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Research Grant: Novartis, Roche, AstraZeneca, Seagen, Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca. V.C. Dieras: Financial Interests, Personal, Advisory Board, National advisory board: Pierre Fabre Oncologie; Financial Interests, Personal, Advisory Board, Steering Committee, consultant, Symposium, travel expenses: Roche Genentech; Financial Interests, Personal, Advisory Board, + Symposia and travel expenses: Novartis; Financial Interests, Personal, Advisory Board, Advisory boards, symposia, travel expenses: Pfizer; Financial Interests, Personal, Advisory Board, Symposia, travel expenses: Lilly, AstraZeneca, MSD; Financial Interests, Personal, Advisory Board, Symposia, travel expenses: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, symposia, travel expenses: Seagen, Gilead; Financial Interests, Personal, Advisory Board, Steering Committee: AbbVie; Financial Interests, Personal, Advisory Board: Eisai, Medac GmbH; Financial Interests, Personal, Other, IDMC: Sanofi; Financial Interests, Personal, Advisory Board, national board: Menarini; Financial Interests, Personal and Institutional, Other, IDMC: Sanofi; Financial Interests, Institutional, Invited Speaker: Roche Genentech, AstraZeneca; Financial Interests, Institutional, Invited Speaker, Steering Committee: Lilly; Financial Interests, Institutional, Invited Speaker, + IDMC: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, PI: Seagen. V. Massard: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Eli Lilly, Pfizer, Bayer; Financial Interests, Personal, Invited Speaker: Gilead Sciences, Astellas Pharma, Janssen Pharmaceuticals, Laboratoires Pierre Fabre; Financial Interests, Institutional, Funding: AstraZeneca. F. Dalenc: Non-Financial Interests, Principal Investigator: Roche, AstraZeneca, Gilead, Novartis. A. Gonçalves: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, MSD, innate pharma, Parexel, Gilead; Financial Interests, Institutional, Invited Speaker: Novartis, Roche, MSD, AstraZeneca, Daiichi Sankyo; Other, travel accommodation meeting registration: Mylan; Other, travel accommodation meeting registration: Novartis; Other, travel, accommodation, meeting registration: Roche, Menarini. C. Bailleux: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca; Financial Interests, Personal, Invited Speaker: Novartis, Lilly, Seagen, AstraZeneca; Financial Interests, Personal, Stocks/Shares, <1%: SigBio. J. Frenel: Financial Interests, Personal, Advisory Board: Pfizer, Novocure, Pierre Fabre, Eisai, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: GSK, Amgen, Eisai; Financial Interests, Institutional, Advisory Board: Exact Science, Lilly, Daiichi Sankyo, AstraZeneca, Clovis Oncology; Financial Interests, Institutional, Invited Speaker: Novartis, MSD; Financial Interests, Invited Speaker: AstraZeneca, Seagen, MSD, Daiichi Sankyo; Non-Financial Interests, Principal Investigator: Novartis, Lilly, AstraZeneca, Pfizer, Daiichi Sankyo, MSD. L. Bosquet: Financial Interests, Institutional, Full or part-time Employment, In charge of scientific projects at Unicancer, Health Data and Partnership Department: Unicancer. S. Delaloge: Financial Interests, Institutional, Advisory Board: Novartis, Sanofi, Gilead; Financial Interests, Institutional, Invited Speaker: Pfizer, Roche Genentech, BMS, Sanofi; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Invited Speaker, ESMO symposium: Gilead; Financial Interests, Institutional, Advisory Board, scientific board: Elsan; Non-Financial Interests, Member of Board of Directors, Société Française de Sénologie et Pathologie Mammaire: SFSPM; Non-Financial Interests, Principal Investigator, H2020 funding: European Commission. N.U. Lin: Financial Interests, Personal, Advisory Board, Ad board participation: Seattle Genetics, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Ad board/Steering Committee participation; consultant: AstraZeneca; Financial Interests, Personal, Advisory Board, Ad board/Steering committee participation; travel support: Olema Pharmaceuticals; Financial Interests, Personal, Other, Consultant: Blueprint Medicines, Janssen; Financial Interests, Personal, Other, High level Consulting: Artera Inc.; Financial Interests, Personal, Other, Steering committee: Stemline/Menarini; Financial Interests, Personal, Royalties, Royalties for book chapter(s): Up to Date; Financial Interests, Institutional, Funding, Trial funding to institute (and steering committee): Olema Pharmaceuticals, AstraZeneca, Seattle Genetics; Financial Interests, Institutional, Funding, Trial funding to institute: Zion Pharmaceuticals; Financial Interests, Institutional, Funding, trial funding to institute: Pfizer, Genentech. W. Jacot: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Daiichi Sankyo Sankyo; Financial Interests, Personal, Advisory Board: Eisai, Novartis, Roche, Pfizer, Eli Lilly, MSD, BMS, Chugai, Gilead. H.A. Parsons: Financial Interests, Institutional, Funding: Puma Biotechnology; Financial Interests, Personal, Advisory Board: Illumina; Financial Interests, Advisory Board: Caris. All other authors have declared no conflicts of interest.