The combination of docetaxel (D) with trastuzumab and pertuzumab (T+P) remains the standard first-line in metastatic HER2-positive breast cancer (BC), based on the results of the CLEOPATRA trial. However, all patients (pts) do not benefit equally from this therapy. We explored the association between survival outcomes and initial tumoral response to D+T+P.
We performed an exploratory analysis of CLEOPATRA (NCT00567190) using data extracted from the Vivli database (ID:00007856). The primary objective was to assess the overall survival (OS) of pts treated with D+T+P according to their response at the first tumor assessment at 9 weeks. Secondary objective was progression-free survival (PFS). Response was classified as complete (CR), partial (PR), or stable (SD), according to RECIST1.0 based on central review as per original trial. Pts without first tumor assessment were excluded. We performed a log-rank test to compare Kaplan-Meier curves, and uni- and multivariate analysis. We applied Extended Cox Regression Model to consider a possible guarantee-time bias.
In D+T+P arm, 362/402 pts were included: 12.7% (46/62) with CR, 67.1% (243/362) with PR, and 20.2% (73/362) with SD. In CR group, 47.8% of pts had de novo disease (61.3% in PR, 43.8% in SD, Fisher’s exact test p=0.015), 69.6% had visceral disease (83.3% in PR, 67.1% in SD, p=0.005), 60.9% were hormone receptor (HR) negative (51.9% in PR, 49.3% in SD, p=NS). After a median (m) follow-up of 4.1 years, pts in CR group had a significantly longer PFS compared to PR or SD (log-rank p<0.001), and a longer OS compared to PR or SD (mOS not reached (NR), 57.3 mo (interquartile (IQR) 32.1-NR) and 43.4 mo (IQR 22-103.5) in the CR, PR, and SD group, respectively, p=0.002). In multivariate analysis, a high body mass index was associated with better OS in SD group (HR=0.93 95%; confidence interval (CI) (0.88-0.99) p=0.023), ECOG ≥1 with worse OS in PR group (HR=1.66 95% CI (1.17-2.36) p=0.005). The outcome benefit of CR was equal in HR- and HR+ tumors, p=NS.
Obtaining an early radiological CR with D+T+P confers significantly longer OS and PFS, whereas no difference is observed once compared with PR and SD.
Institut Jules Bordet.
Has not received any funding.
E. Agostinetto: Financial Interests, Personal, Invited Speaker: Eli Lilly, Sandoz, AstraZeneca; Financial Interests, Personal, Royalties: Eli Lilly, Roche, Novartis, Genetics, Istituto Gentili, Daiichi Sankyo. C. Molinelli: Financial Interests, Personal, Royalties: Novartis, Lilly. D. Martins Branco: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Novartis, Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Other, Meeting/travel grant: Novartis, Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant, Institutional funding for an observational research project: Novartis; Financial Interests, Institutional, Research Grant, Institutional funding for an investigator-initiated clinical trial: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Invited Speaker: 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; Non-Financial Interests, Leadership Role, Oncology Committee Chair: January 2020 - January 2021: Health Parliament Portugal. G. Nader Marta: Financial Interests, Personal, Royalties: Roche, Bayer. M. Lambertini: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: Takeda, Sandoz, Ipsen, Libbs, Knight, Daiichi Sankyo, Lilly, Pfizer, Novartis, Roche; Financial Interests, Personal, Other, Travel grant to attend ASCO 2022: Gilead; Financial Interests, Institutional, Invited Speaker, 2-year research grant paid to my Institution: Gilead. E. de Azambuja: Financial Interests, Personal, Advisory Board: Roche/GNE, Novartis, Seagen; Financial Interests, Personal, Invited Speaker: Zodiac, Libbs, Pierre Fabre, Lilly, AstraZeneca; Financial Interests, Institutional, Research Grant: Roche/GNE, AstraZeneca, GSK/Novartis, Servier; Financial Interests, Institutional, Other, Travel Grant: Roche/GNE; Financial Interests, Institutional, Invited Speaker: MSD, ABCSG, Nektar, Gilead, Immunomedics, Synthon, Odonate Therapeutics; Financial Interests, Invited Speaker, Chair of the Gilead Sciences Research Scholars Program in Solid Tumours: Gilead; Financial Interests, Invited Speaker, Aphinity, Lorelei, Impassion03: Roche; Financial Interests, Invited Speaker, AURORA: Breast International Group; Financial Interests, Invited Speaker, Olympia: Astra-Zeneca; Financial Interests, Personal, Other, Travel grant: Astra-Zeneca; Non-Financial Interests, Advisory Role, Member of the cardio-oncology council: European Society for 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. All other authors have declared no conflicts of interest.