241P - Overall survival and updated invasive disease free survival results from the Penelope-B trial investigating palbociclib vs placebo for patients with high-risk HR+/HER2- breast cancer and residual disease after NACT

Background

Addition of palbociclib (palb) to endocrine therapy (ET) in hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) patients (pts) at high-risk of relapse after taxane-based neoadjuvant chemotherapy (NACT) did not improve invasive disease-free survival (iDFS) compared to a placebo (pb).

Methods

The PENELOPE-B trial (NCT01864746) enrolled 1250 pts with HR+/HER2- primary BC with residual disease and high risk of relapse (CPS-EG score ≥3 or 2 and ypN+) after taxane-based NACT. Pts were randomly assigned to receive either palb 125mg or pb each d1-21 q4w for 13 cycles alongside ET followed by standard ET. This is preplanned analysis of overall survival (OS) with prolonged follow-up (FU).

Results

After a median FU of 77.8 months, we recorded 225 deaths [(108 palb; 117 pb) hazard ratio (HR) 0.87, 95% CI 0.67-1.14, p=0.31] with a 6-year OS rate of 82.4% vs. 80.3%. No significant improvement was noted for palb vs pb for iDFS, distant disease free survival (DDFS) or locoregional relapse rate (LRR) even with longer FU. Upon stratified analysis, we found no discernible benefits across the major subgroups considered for any of the endpoints. However, in exploratory analyses for lobular BC subtype a notable trend for better survival outcomes was observed in pts receiving palb (n=58) compared to pb (n=52) with a HR of 0.45 (95% CI 0.19-1.07, p=0.063) for OS and estimated 6-year rates for OS/DDFS/iDFS of 88.8%/73.5%/73.5% (palb) vs. 73.2%/51.1%/51.1% (pb), p=0.058 for DDFS and p=0.035 for iDFS. Out of 22 observed deaths (n=8 palb vs. n=14 pb), 21 were related to BC. Multivariate analysis indicated that higher nodal burden after NACT (ypN2-3), larger tumor size after NACT (ypT3/4), CPS-EG Score ≥3 and Ki67 >15% were independent prognostic factors for poorer outcome in terms of OS, iDFS and DDFS.

Conclusions

Despite long FU, no notable survival improvement was observed with palb over pb in all survival endpoints. A promising trend was seen in lobular BC pts treated with palb, but these results are limited by a small sample size and exploratory nature of the analysis.

Clinical trial identification

NCT01864746.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Pfizer Inc.

Disclosure

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, Advisory Board, 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. M. Martin Jimenez: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Roche/Genentech, Daiichi Sankyo, Menarinio-Stemline; Financial Interests, Personal, Invited Speaker: Pfizer, Astrazeneca, Lilly, Novartis, Roche/Genentech; Financial Interests, Institutional, Research Grant: Novartis, Roche, Puma; Non-Financial Interests, Member of Board of Directors: Trio; Non-Financial Interests, Leadership Role: GEICAM; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Advisory Board: SEOM. S. Kim: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Lilly, DaeHwa Pharma, ISU Abx, Daiich-Sankyo, BeiGene, Samsung Bioepics, OBI pharma; Financial Interests, Personal, Invited Speaker: Legochem Bioscience; Financial Interests, Personal, Ownership Interest: Genopeaks; Financial Interests, Institutional, Research Grant: Novartis, Sanofi-Genzyme, DongKook Pharm Co. H.D. Bear: Financial Interests, Personal, Stocks or ownership, Stock ownership: Pfizer. K.A. Gelmon: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Lilly, Novartis, Merck, Gilead, Seagen, City of Hope, Celcuity; Financial Interests, Institutional, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Local PI: Pfizer, BMS. C.M. Kelly: Financial Interests, Personal, Advisory Board: Novartis, Daiichi Sankyp, AstraZeneca; Financial Interests, Personal, Other, Conference attendance/travel expenses: Novartis; Non-Financial Interests, Personal, Other, Steering Committee Member Destiny Breast 11: AstraZeneca. M. Toi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Devicore medical Japan, Eisai, Exact Science, MSD, Nippon-Kayaku, Novartis, Pfizer, Shimadzu, Sysmex, Taiho, Takeda, Yakult; Financial Interests, Personal, Advisory Board, This company is not working anymore: Athenex Oncology; Financial Interests, Personal, Advisory Board: BMS, Bertis, Kansai Medical Net, Terumo; Financial Interests, Personal, Advisory Board, + Invited speaker: Daiichi Sankyo, Eli Lilly and companies; Financial Interests, Personal, Invited Speaker, + Invited speaker: Kyowa-Kirin; Financial Interests, Institutional, Research Grant, Research grant to a basic study: AFI technology, Astellas, Luxonus, Sanwa Shurui; Financial Interests, Institutional, Research Grant, Research grant to a basic-cliical studySteering committee member (non-financial interest): AstraZeneca; Financial Interests, Institutional, Research Grant, Research Grant to Institution, Funding to InstitutionCoordianting PI (non-finacial interest), Steering Committee member (non-financial interest), Local PI (non-finacial interest): Chugai; Financial Interests, Institutional, Research Grant, Research grant to a preclinical study Steering committee member (non-financial interest): Daiichi Sankyo; Financial Interests, Institutional, Funding, Funding to a clinical studyCoordinating PI of a neoadjuvant study (non-financial interest): Eisai; Financial Interests, Institutional, Funding, Funding to a clinical studySteering committee member (non-financial interest): Eli Lilly and companies; Financial Interests, Institutional, Research Grant, Research grant to a clinical study: GL Science, Yakult; Financial Interests, Institutional, Research Grant, Research grant to a basic-clinical study: Nippon-Kayaku; Financial Interests, Institutional, Funding, Research Grant to InstitutionCoordianting PI (non-finacial interest): Pfizer; Financial Interests, Institutional, Research Grant, Research grant to a basic investigation: Shimadzu; Financial Interests, Institutional, Research Grant, Research grant to clinical study: Takeda; Financial Interests, Institutional, Funding, Funding to translational research of JBCRG assoc. studies: The Japan Breast Cancer Research Group association; Financial Interests, Institutional, Funding, Funding to translational research of KBCRN assoc studies: The Kyoto Breast Cancer Research Network association; Financial Interests, Institutional, Research Grant, Research grant to a study: Kansai medical Net; Non-Financial Interests, Member of Board of Directors, No salary: The Japanese Onco-Cardiology Society, The Kyoto Breast Cancer Research Network association, The Japan Breast Cancer Research group association, Organisation for Oncology and Translational Research; Non-Financial Interests, Leadership Role, No salary: The Japanese Breast cancer Society; Other, Editorial board member: British Journal of Cancer, Asian Journal of Surgery, Asian Journal of Breast Surgery, Translation Breast Cancer Research; Other, Associate editor: Scientific Reports, Breast Cancer Research and Treatment, Cancer Science, Frontiers in Women's Cancer. H.S. Rugo: Financial Interests, Personal, Other, Consultancy/advisory support: NAPO, Mylan/Viatris, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Local PI: Novartis, Lilly, Pfizer, Daiichi, AstraZeneca, Gilead Sciences, Inc.; Financial Interests, Institutional, Coordinating PI: OBI Pharma, F. Hoffmann-La Roche AG/Genentech, Inc., Merck; Financial Interests, Institutional, Research Grant: Stemline Therapeutics, Ambryx; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. M.I. Gnant: Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, PierreFabre, Amgen, EPG Health; Financial Interests, Personal, Advisory Board: DaiichiSankyo, EliLilly, MSD, Menarini-Stemline, Veracyte; Financial Interests, Personal, Member of Board of Directors: ABCSG GmbH, ABCSG Research Services GmbH; Financial Interests, Trial Chair: Pfizer; Financial Interests, Steering Committee Member: AstraZeneca, EliLilly; Other, Spouse is employed by Sandoz: Sandoz. N. Hirmas: Financial Interests, Institutional, Funding: Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche, Seagen, AbbVie, AstraZeneca, BMS, Daiichi Sankyo, Gilead, Molecular Health, Novartis, Roche, Pfizer. V. Nekljudova: Financial Interests, Institutional, Funding: Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche, Seagen, AbbVie, AstraZeneca, BMS, Daiichi Sankyo, Gilead, Molecular Health, Novartis, Roche, Pfizer. F. Marmé: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK/Tesaro, Clovis, Pfizer, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Novartis, Roche, Gilead/immunomedics, EISAI, PharmaMar, GenomicHealth, Myriad, Seagen; Financial Interests, Institutional, Invited Speaker: Seagen, Daiichi Sankyo, GSK, AstraZeneca, Stemline Menarini; Financial Interests, Institutional, Advisory Board: Roche, Immunicom; Financial Interests, Institutional, Local PI: Roche, Novartis, Eisai, MSD, Vaccibody, GSK; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Roche, Gilead/Immunomedics, German Breast Group, AGO Research GmbH; Financial Interests, Institutional, Funding: AstraZeneca, Lilly, Seagen. All other authors have declared no conflicts of interest.