111MO - Tailored dose-dense versus standard adjuvant chemotherapy for high-risk early breast cancer: Efficacy outcomes and key subgroups after 10 years of follow-up in the randomized phase III PANTHER trial

Background

An individual patient-level meta-analysis has shown that dose dense adjuvant chemotherapy administered every two weeks leads to superior outcomes compared to standard regimens every three weeks. However, most studies used the suboptimal three-weekly paclitaxel as control and were carried out before the introduction of adjuvant trastuzumab and extended endocrine therapy.

Methods

PANTHER is an international, randomized phase III trial which compared 4 cycles of leukocyte nadir-based tailored and dose-dense adjuvant epirubicin and cyclophosphamide every 2 weeks followed by 4 cycles of tailored dose-dense docetaxel every 2 weeks (tDD EC/D), or to standard-interval chemotherapy with 3 cycles of fluorouracil and epirubicin-cyclophosphamide every 3 weeks followed by 3 cycles of docetaxel every 3 weeks. The primary end point was breast cancer recurrence-free survival (BCRFS). The primary analysis at 5 years (Foukakis et al JAMA 2016) demonstrated an improvement of event-free survival with dose-dense therapy but no significant difference in BCRFS.

Results

Between February 2007 and September 2011, 2017 patients were enrolled in the trial and 2003 patients comprise the intention-to-treat population. After a median follow-up of 10.3 years (interquartile range, 9.1 – 10.5 years), there were 179 breast cancer relapses in the experimental and 218 in the control group. Treatment with tDD EC/D improved the primary endpoint of BCRFS (HR=0.80, 95% CI 0.65 – 0.98, p=0.030; 10-year event rate 18.6% vs 22.3%, absolute difference 3.7% ± 1.9%). The improvement in BCRFS was noted across subgroups according to hormone receptor and HER2 expression, anatomic stage, and other demographic and pathologic factors. The difference in overall survival was not statistically significant (HR=0.82, 95% CI 0.65 – 1.04, p=0.109; 10-year event rate 15.1% vs 16.6%, absolute difference 1.5% ± 1.7%).

Conclusions

After 10 years of follow-up in the PANTHER trial, tailored dose-dense adjuvant chemotherapy improved BCRFS compared with standard adjuvant chemotherapy containing 3-weekly docetaxel.

Clinical trial identification

NCT00798070.

Legal entity responsible for the study

Karolinska University Hospital Karolinska Un.

Funding

This study was supported by grants from the Swedish Cancer Society to the Karolinska Institutet, from the Swedish Breast Cancer Association (Bröstcancerförbundet), from the research funds at Radiumhemmet, and from Amgen, Roche, and Sanofi-Aventis to the Swedish Breast Cancer Group (SweBCG) at Karolinska University Hospital, the German Breast Group (GBG), and the Austrian Breast & Colorectal Cancer Study Group (ABCSG).

Disclosure

T. Foukakis: Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Gilead Sciences; Financial Interests, Personal, Royalties, Authorship of two chapters in UpToDate: Wolters Kluwer; Financial Interests, Institutional, Invited Speaker, Clinical trial support (research grant and study drug): AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical trial support (research grant and study drug): Novartis; Financial Interests, Institutional, Invited Speaker, Discount on the Prosigna PAM50 assay in ARIADNE clinical trial: Veracyte. A. Matikas: Financial Interests, Institutional, Invited Speaker: Seagen; Financial Interests, Institutional, Invited Speaker, International co-PI of academic trial ARIADNE (EU CT: 2022-501504-95-00): AstraZeneca, Novartis, Veracyte; Financial Interests, Institutional, Invited Speaker, Registry study: Merck; Non-Financial Interests, Advisory Role: Veracyte, Roche. R. Greil: Financial Interests, Personal, Advisory Board: Celgene, Novartis, Roche, BMS, Takeda, AbbVie, AstraZeneca, Janssen, MSD, Merck, Gilead, Daiichi Sankyo, Sanofi; Financial Interests, Institutional, Stocks/Shares: Novo Nordisk, Lilly; Financial Interests, Personal and Institutional, Funding: Celgene, Roche, Merck, Takeda, AstraZeneca Novartis, Amgen, BMS, MSD, Sandoz, AbbVie Gilead, Daiichi Sankyo; Non-Financial Interests, Other, Travel, Accommodation, Expenses, Consulting, Adv Role: Roche, Amgen, Janssen, AstraZeneca Novartis, MSD, Celgene, Gilead, BMS, AbbVie, Daiichi Sankyo, Sanofi; Other, Travel, Accommodations, Expenses, Consulting, Adv Role., Honoraria: Roche, Amgen, Janssen, AstraZeneca Novartis, MSD, Celgene, Gilead, BMS, AbbVie, Daiichi Sankyo, Sanofi. G.G. Steger: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Novartis, Lilly, Pfizer; Non-Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis, TEVA, Pfizer. M. Untch: Financial Interests, Personal, Invited Speaker: Agendia, AstraZeneca, Daiichi Sankyo, Eisai, Gilead, Lilly Deutschland, MSD, Myriad Genetics, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi Aventis, Seagen, Stemline. T. Fornander: Financial Interests, Personal, Stocks/Shares: Pfizer. P. Malmstrom: Financial Interests, Personal, Royalties: PFS Genomics. M.I. Gnant: Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pierre Fabre, Amgen, EPG Health; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Eli Lilly, MSD, Menarini-Stemline; Financial Interests, Personal, Expert Testimony: Veracyte; Financial Interests, Personal, Member of Board of Directors: ABCSG GmbH, ABCSG Research Services GmbH; Financial Interests, Invited Speaker: Pfizer, AstraZeneca, Eli Lilly; Other, Spouse is employed by Sandoz: Sandoz. S. Loibl: Financial Interests, Institutional, Advisory Board, Member: Amgen, AstraZeneca, BMS, Celgene, DSI, EirGenix, GSK, Lilly, Pierre Fabre, Roche, Seagen, AbbVie, Sanofi, Gilead, Merck, Novartis, Relay Therapeutics; Financial Interests, Institutional, Invited Speaker: AstraZeneca, DSI, Novartis, Pfizer, Roche, Gilead, Seagen, Stemline-Menarini; Financial Interests, Institutional, Advisory Board: Pfizer, Olema; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Personal, Full or part-time Employment, CEO: GBG Forschungs GmbH; Financial Interests, Institutional, Invited Speaker, Ki67 Quantifier: VMscope GmbH; Financial Interests, Institutional, Research Grant: AstraZeneca, Celgene, Novartis, Immunomedics/Gilead, Pfizer, Roche, Daiichi Sankyo; Financial Interests, Institutional, Funding: AbbVie, Molecular Health, Greenwich Life Sciences; Financial Interests, Personal, Other, PIPenelope/Padma: Pfizer; Financial Interests, Personal, Other, SC PALOMA3: Pfizer; Financial Interests, Personal, Other, SC SOLAR1: Novartis; Financial Interests, Personal, Other, SC ASCENT: Immunomedics/Gilead; Financial Interests, Personal, Other, SC HERCLIMB: Seagen; Financial Interests, Personal, Other, SC Katherine: Roche; Financial Interests, Personal, Other, SC Capitello; EC Cambria 1: AstraZeneca; Financial Interests, Personal, Other, SC Inavo: Roche; Financial Interests, Personal, Other, SC Destiny B05; SC Destiny B09: Daiichi Sankyo; Non-Financial Interests, Principal Investigator, After publication of primary endpoint: PI Aphinity; Non-Financial Interests, Advisory Role, Group in Germany responsible for breast cancer guidelines: AGO Kommission Mamma; Non-Financial Interests, Member, German Gynaecological Oncology society: AGO; Non-Financial Interests, Member, German Cancer Society: DKG; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member, Member guideline committee; past chair in ESMO Breast: ESMO; Other, EP14153692.0No financial interest, Institutional: Patent; Other, EP21152186.9No financial interest, institutional: Patent; Other, EP19808852.8 No financial interest, Institutional: Patent. J. Bergh: Other, Fees (honoraria) to Coronis and Asklepios Cancer Research AB as an invited speaker/chair from AstraZeneca and Roche, respectively: Coronis and Asklepios Cancer Research AB.; Other, Institutional honoraria as chapter co-author for UpToDate to Asklepios Medicin HB. Co-author on a chapter on ”Prognostic and Predictive factors in early, non-metastatic breast cancer”: Asklepios Medicin; Other, Institutional research grants received more than ten years ago to Karolinska Institutet and/or University Hospital for molecular marker studies/ clinical studies (we are still working with the material). No personal payments for these activities: Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche and Sanofi-Aventis; Other, Stocks in Stratipath AB. The company is involved in AI based diagnostics for breast cancer: Stratipath AB. All other authors have declared no conflicts of interest.