All times are listed in CEST (Central European Summer Time)
59MO - Adjuvant Abemaciclib Combined with Endocrine Therapy (ET): Efficacy Results in monarchE Cohort 1 (ID 1)
- Mattea Reinisch (Essen, Germany)
- Masakazu Toi (Kyoto, Japan)
- Frances Boyle (North Sydney, Australia)
- Young-Hyuck Im (Seoul, Korea, Republic of)
- David Molthrop (Lake Mary, United States of America)
- Zefei Jiang (Beijing, China)
- Ran Jennifer Wei (Indianapolis, United States of America)
- Francisco Sapunar (Indianapolis, United States of America)
- Brenda Grimes (Indianapolis, United States of America)
- Sarah C. Nabinger (Indianapolis, United States of America)
- Stephen R. Johnston (London, United Kingdom)
Abstract
Background
Abemaciclib (oral CDK4 & 6 inhibitor) plus ET as adjuvant treatment for HR+, HER2- high risk early breast cancer (EBC), previously demonstrated robust benefit with an acceptable safety profile in the monarchE trial. Here we present efficacy data in a monarchE patient population (Cohort 1) which has a high risk of recurrence, can easily be identified in clinical practice, and recently received regulatory approval.
Methods
monarchE, a global, phase 3 trial, randomly assigned (1:1) 5637 patients to receive ET +/- adjuvant abemaciclib into 2 cohorts. Cohort 1 (C1) enrolled 5120 patients with either ≥4 positive axillary lymph nodes (pALN), or 1-3 pALN plus additional high risk features of Grade 3 disease and/or tumor ≥5 cm. Cohort 2 enrolled 517 patients, was previously described, and data are immature.
Results
With 28 months median follow-up in C1 (data cut off April 2021), the 17% risk of recurrence at 3Y in the ET alone arm confirms the high risk nature of this patient population. Abemaciclib+ET demonstrated a clinically meaningful benefit in reducing the risk of developing an IDFS event by 32% (absolute benefit of 5.7% at 3Y) and a DFRS event by 33% (4.5% absolute benefit at 3Y)(Table). Within C1, consistent treatment benefit in IDFS and DRFS was seen in subgroups of patient and disease characteristics. Safety analyses, conducted on the entire safety population, were consistent with the known profile of abemaciclib. DRFS: distant relapse-free survival; IDFS: invasive disease-free survival
Abemaciclib+ET (N=2555) ET Alone (N=2565) HR (95% CI) IDFS IDFS Events, n 218 318 IDFS: 0.680 (0.572-0.808) 2-Year IDFS Rates, % (95% CI) 92.6 (91.4-93.5) 89.6 (88.3-90.8) 3-Year IDFS Rates, % (95% CI) 88.6 (86.7-90.1) 82.9 (80.7-84.8) DRFS DRFS Events, n 179 266 DRFS: 0.669 (0.554-0.809) 2-Year DRFS Rates, % (95% CI) 94.1 (93.0-95.0) 91.2 (90.0-92.3) 3-Year DRFS Rates, % (95% CI) 90.2 (88.4-91.7) 85.7 (83.6-87.5)
Conclusions
As C1 comprises 91% of the patients in monarchE, C1 drives the robust benefit observed in the ITT population. C1 data demonstrate substantial evidence of the benefit of adjuvant abemaciclib+ET in patients with HR+, HER2- EBC at high risk of recurrence who can be identified easily as part of routine diagnostic breast cancer workup.
Clinical trial identification
NCT03155997.
Editorial acknowledgement
Medical writing support and editorial assistance were provided by Eglantine Julle-Daniere, employee of Eli Lilly and Company.
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company.
Disclosure
M. Toi: Financial Interests, Personal, Advisory Board, + Invited speaker: Kyowa-Kirin, Daiichi Sankyo, Eli Lilly and Companies; Financial Interests, Personal, Advisory Board: BMS, Athenex Oncology, Bertis, Terumo, Kansai Medical Net; Financial Interests, Personal, Invited Speaker: Chugai, Takeda, Pfizer, Taiho, Eisai, AstraZeneca, MSD, Exact Science, Novartis, Shimadzu, Yakult, Nippon-Kayaku, Devicore Medical Japan; Financial Interests, Institutional, Research Grant, Research Grant to Institution, Funding to Institution Coordianting PI (non-finacial interest), Steering Committee member (non-financial interest), Local PI (non-finacial interest): Chugai; Financial Interests, Institutional, Research Grant, Research grant to clinical study: Takeda, Yakult, GL Science; Financial Interests, Institutional, Funding, Research Grant to Institution Coordinating PI (non-finacial interest): Pfizer; Financial Interests, Institutional, Research Grant, Research grant to a preclinical study: Kyowa-Kirin; 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, Funding, Funding to a clinical study Coordinating PI of a neoadjuvant study (non-financial interest): Eisai; Financial Interests, Institutional, Funding, Funding to a clinical study Steering committee member (non-financial interest): Eli Lilly and companies; Financial Interests, Institutional, Research Grant, Research grant to a preclinical study Steering committee member (non-financial interest): Daiichi Sankyo; Financial Interests, Institutional, Research Grant, Research grant to a basic-cliical study Steering committee member (non-financial interest): AstraZeneca; Financial Interests, Institutional, Research Grant, Research grant to a basic study: Astellas, AFI technology, Luxonus; Financial Interests, Institutional, Research Grant, Research grant to a basic investigation: Shimadzu; Financial Interests, Institutional, Research Grant, Research grant to a basic-clinical study: Nippon-Kayaku, Shionogi; Non-Financial Interests, Invited Speaker, 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; Other, Deputy Editor: International Journal of Oncology; Other, Associate editor: British Journal of Cancer, Scientific Reports, Breast Cancer Research and Treatment, Cancer Science, Frontiers in Women's Cancer, Asian Journal of Surgery, Asian Journal of Breast Surgery. F. Boyle: Financial Interests, Personal, Advisory Role: Roche, Pfizer, Eli Lilly and Company, and Novartis; Financial Interests, Personal, Other, Honoraria: Roche, Pfizer, Eli Lilly and Company, and Novartis. M. Reinisch: Financial Interests, Other, Personal fees: AstraZeneca, MSD, Eli Lilly and Company, Roche, Novartis, Daiichi Sankyo, Seagen, Pfizer, Somatex; Non-Financial Interests, Other, Travel: Novartis, Pfizer. R.J. Wei, F. Sapunar, B. Grimes: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. S.C. Nabinger: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. S.R.D. Johnston: Financial Interests, Personal, Other, Consulting/Advisory Role: Eli Lilly, Puma Biotechnology; Financial Interests, Personal, Other, Consulting/Advisory Role and Speakers Bureau: AstraZeneca, Pfizer, Novartis; Financial Interests, Personal, Other, Speakers Bureau: Eisai. Roche/Genentech; Financial Interests, Institutional, Funding, Research funding for lab studies and clinical trials: Pfizer; Financial Interests Institutional, Funding, Research funding for lab studies: Puma Biotechnology; Financial Interests, Institutional, Funding, Research funding for clinical trials: Eli Lilly, AstraZeneca, Novartis, Roche/Genentech. All other authors have declared no conflicts of interest.
60MO - Ovarian function in young patients (pts) treated with postneoadjuvant palbociclib (PAL) and endocrine therapy (ET) for hormone receptor (HR)-positive, HER2-negative early breast cancer (BC): explorative analysis in Penelope-B (ID 2)
- Jenny Furlanetto (Neu-Isenburg, Germany)
- Frederik Marmé (Mannheim, Germany)
- Christian Thode (Jever, Germany)
- Valentina Nekljudova (Neu-Isenburg, Germany)
- Yuan Liu (San Diego, United States of America)
- Miguel Martin Jimenez (Madrid, Spain)
- Toralf Reimer (Rostock, Germany)
- Erik Knudsen (Buffalo, New York, United States of America)
- Carsten Denkert (Marburg, Germany)
- Martina Bassy (Jever, Germany)
- Lesley-Ann Martin (London, United Kingdom)
- Thomas Karn (Frankfurt am Main, Germany)
- Bruno V. Sinn (Berlin, Germany)
- Martin Filipitis (Vienna, Austria)
- Marion Van Mackelenbergh (Kiel, Germany)
- Peter A. Fasching (Erlangen, Germany)
- Volkmar Müller (Hamburg, Germany)
- Elmar Stickeler (Aachen, Germany)
- Christian Schem (Hamburg, Germany)
- Sibylle Loibl (Neu-Isenburg, Germany)
Abstract
Background
PENELOPE-B is a phase III study investigating the role of PAL + ET vs placebo + ET in HR+, HER2- early BC pts with high risk of relapse after neoadjuvant chemotherapy (NACT). Invasive disease-free survival was not improved with PAL + ET (Loibl JCO 2021). Estradiol (E2), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH) values might be influenced by post-NACT PAL. Changes in hormones for pts treated with CDK4/6 inhibitors + ET are not well explored.
Methods
616 pts were premenopausal at baseline (BL, investigator-defined). Pts with serum samples at BL and at least before cycle (C) 7 or at end of treatment (EOT) were considered (N=576). 576 pts provided blood samples at BL, 526 before C7, 541 at EOT. Centrally assessed FSH>12.4 IU/l and E2<52.2 ng/L were defined as postmenopausal; fertile level of AMH as ≥0.22 ng/mL (central lab cut-offs). Analysed subgroups were pre- vs postmenopausal FSH/E2 at BL, age ≤40 vs >40 yrs, gonadotropin-releasing hormone analogue (GnRHa) use vs no.
Results
Median age was 43 (19-56) yrs; 46.8% pts had BMI <25, 53.2% ≥25. Hormone values are shown below. At BL, 41.6% of pts in the placebo vs 41.3% in the PAL arm had premenopausal hormone levels. Of these, 9.1 vs 13.5% (p=0.387) had postmenopausal hormone levels at C7. In pts ≤40 yrs 29.2 vs 29.5% at BL (p=1.000), 18.1 vs 23.4% at C7 (p=0.472) had postmenopausal values. More pts >40 yrs (BL 75.3%, C7 69.8%) vs ≤40 yrs (29.4, 20.7%) and without GnRHa (80.3, 72.2%) vs with (15.9, 12.1%) had postmenopausal hormone levels. Median AMH was under the detection limit at all time points. At BL 91.8 vs 93.6% had non-fertile levels of AMH (p=0.426), 94.4 vs 96.5% at C7 (p=0.298), without difference in subgroups. EOT analysis will be presented at the meeting. Detectable threshold, dt: E2=5 ng/L; P, placebo
Median, IQR FSH IU/l E2 ng/L PAL P p-value PAL P p-value BL 35.6 7.1-55.5 32.5 6.3-54.2 0.407 dt 2.5-13.0 dt 2.5-14.0 0.242 C7 24.1 5.5-37.7 18.4 5.1-34.3 0.157 dt 2.5-10.0 dt 2.5-10.0 0.726 BL 5.6 3.2-11.2 5.5 3.1-9.0 0.571 6.0 2.5-105.0 7.0 2.5-125.0 0.768 C7 4.8 2.5-14.4 4.6 2.3-8.8 0.258 dt dt-14.0 dt dt-13.0 0.940 BL 10.6 3.8-46.9 7.6 4.4-41.5 0.878 8.0 dt-74.0 7.5 dt-55.0 0.910 C7 8.0 2.9-32.1 5.2 2.7-16.9 0.150 5.0 dt-55.0 dt dt-22.0 0.448 BL 5.1 3.1-10.6 5.0 3.1-9.0 0.731 dt dt-8.0 dt dt-9.0 0.792 C7 3.5 2.2-7.0 4.3 2.2-8.0 0.489 dt dt-5.0 dt dt-6.0 0.574
Conclusions
PAL does not influence FSH, E2 and the ovarian reserve significantly when added to ET after NACT.
Clinical trial identification
NCT01864746.
Legal entity responsible for the study
German Breast Group.
Funding
Funding and drug were provided by Pfizer.
Disclosure
F. Marmé: Financial Interests, Personal, Other, Personal Fees: Roche, AstraZeneca, Pfizer, Tesaro, Novartis, Amgen, PharmaMar, Genomic Health, CureVac, Eisai, BMS, Clovis, Janssen-Cilag, GSK, MSD, Seagen, Myriad, Pierre Fabre; Financial Interests, Personal and Institutional, Research Grant, Grant: Gilead/immunomedics. Y. Liu: Financial Interests, Institutional, Stocks/Shares: Pfizer. M. Martin Jimenez: Financial Interests, Institutional, Research Grant, Grant: Roche; Financial Interests, Institutional, Research Grant, Grant, Consulting/Advisory Fees: Puma; Financial Interests, Institutional, Research Grant, Grant, Consulting/Advisory Fees, Speakers’ Honoraria: Novartis; Financial Interests, Institutional, Advisory Role, consulting/advisory fees, speakers’ honoraria: AstraZeneca, Amgen, Roche, Genentech, Eli Lilly, Pfizer; Financial Interests, Institutional, Advisory Role, consulting/advisory fees: Taiho Oncology, PharmaMar, Daiichi Sankyo. C. Denkert: Financial Interests, Personal, Ownership Interest, Stock and Other Ownership Interests: Sividon Diagnostics; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: MSD Oncology, Daiichi Sankyo, Molecular Health, AstraZeneca, Merck, Lilly; Financial Interests, Personal and Institutional, Advisory Role, Consulting or Advisory Role, Research Funding: Roche; Financial Interests, Institutional, Advisory Role, Research Funding: Myriad Genetics; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: VMScope Digital Pathology Software, WO2015114146A1, WO2010076322A1, WO2020109570A1. T. Karn: Other, Personal, Other, Patent pending: EP18209672. M. van Mackelenbergh: Financial Interests, Institutional, Other, Honoraria: Amgen, AstraZeneca, Roche, Pfizer, Novartis, Lilly, Pierre Fabre, Genomic Health, Molecular Health, Gilead, Seagen, GSK. P.A. Fasching: Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Novartis, Daiichi Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Seagen, Roche, Gilead; Financial Interests, Institutional, Research Grant, Grant: BioNTech, Cepheid; Financial Interests, Personal and Institutional, Advisory Board, Advisory Board, Invited Speaker, Research Grant: Pfizer; Financial Interests, Personal, Advisory Board, Advisory Board: Pierre Fabre, Hexal, Agendia, Sanofi Aventis. V. Müller: Financial Interests, Personal, Invited Speaker, Speaker and Consultancy Honoraria: Amgen, Daiichi Sankyo, MSD, GSK, Gilead; Financial Interests, Personal, Invited Speaker, Speaker Honoraria: AstraZeneca, Eisai, Pfizer, Teva; Financial Interests, Personal and Institutional, Invited Speaker, Speaker and Consultancy Honoraria: Novartis, Roche; Financial Interests, Personal and Institutional, Invited Speaker, Speaker Honoraria: Seagen; Financial Interests, Personal, Advisory Role, Consultancy Honoraria: Genomic Health, Hexal, Pierre Fabre, ClinSol, Lilly; Financial Interests, Institutional, Other, Other: Genentech. E. Stickeler: Financial Interests, Personal, Other, Personal Fees: Roche, Gilead, MSD, Lilly, Pfizer, Seagen, PharmaMar. S. Loibl: Financial Interests, Institutional, Research Grant, honorarium for Ad Boards: AbbVie, Celgene; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board: Amgen, Bayer, BMS, Eirgenix, GSK, Lilly, Merck; Financial Interests, Institutional, Research Grant, honorarium for Ad Boards & Lectures, Grant, Other: AstraZeneca; Non-Financial Interests, Institutional, Research Grant, honorarium for Ad Board & Lecture, Medical Writing: Daiichi Sankyo, Roche; Non-Financial Interests, Institutional, Research Grant, honorarium for Ad Board, Medical Writing: Immunomedics/Gilead; Non-Financial Interests, Institutional, Research Grant, honorarium for Ad Board, Medical Writing: Novartis, Pfizer; Financial Interests, Institutional, Invited Speaker, honorarium for Ad Board & Lecture: Pierre Fabre, prIME/Medscape; Non-Financial Interests, Institutional, Invited Speaker, honorarium for Ad Board, Medical Writing: Puma; Financial Interests, Institutional, Invited Speaker, honorarium for Lecture: Samsung; Non-Financial Interests, Institutional, Invited Speaker, honorarium for Ad Boards, Medical Writing: Seagen; Other, Institutional, Other, Patent Pending: EP14153692.0, EP21152186.9; Other, Institutional, Other, Patent Issued: EP15702464.7; Other, Institutional, Other, Patent Pending, GeparNuevo: EP19808852.8; Other, Institutional, Royalties, Patent Issued, Royalties: Digital Ki67 Evaluator. All other authors have declared no conflicts of interest.
91MO - Randomized trial of neoadjuvant chemotherapy with or without concurrent aromatase inhibitor therapy to downstage ER+ve breast cancer: Breast Cancer Trials group ANZ 1401 ELIMINATE trial. (ID 3)
- Nick Murray (Adelaide, Australia)
- Prudence Francis (Melbourne, Australia)
- Nicholas Zdenkowski (Gateshead, Australia)
- Nicholas Wilcken (Westmead, Australia)
- Frances Boyle (North Sydney, Australia)
- Val Gebski (Sydney, Australia)
- Susan M. Tiley (Gosford, Australia)
- Lesley Gilham (Newcastle, Australia)
- Sarah-Jane Dawson (Melbourne, Australia)
- Sherene Loi (Melbourne, Australia)
- Andrew D. Redfern (Perth, Australia)
- Janine Lombard (Newcastle, Australia)
- Andrew Spillane (Sydney, Australia)
- Clair Shadbolt (Melbourne, Australia)
- Heath Badger (Newcastle, Australia)
Abstract
Background
Chemotherapy (CT) and endocrine therapy (ET) are used sequentially in systemic management of ER+ve HER2-negative early breast cancer, leading to a delay in the initiation of ET. There is little randomized data to assess the benefits/harms of concurrent chemo-endocrine therapy (CET) using aromatase inhibitors (AI). We examined neoadjuvant CT with the addition of letrozole (plus goserelin in pre-/peri-menopausal women) versus CT alone.
Methods
This randomized phase II trial included women with clinical stage 2 or 3, ER+ve HER2-negative grade 2-3 breast cancer suitable for anthracycline and taxane CT, with randomization in a 2:1 ratio to CET or CT. Primary endpoint was proportion of pathologic stage 0 or IA at surgery. The study had 80% power to rule out a 30% rate of down-staging in favour of a rate of 45% in the CET arm with 95% confidence. Pathological complete response (pCR), residual cancer burden (RCB), safety and surgical outcomes were secondary endpoints. Participants underwent pre-and post-treatment breast MRI to determine overall objective radiologic response rate. Patients were evaluable if they received 6 or more cycles of CET or CT in the absence of progression.
Results
134 women were randomized, and 122 evaluable for the primary outcome, 38% postmenopausal, 62% pre-or perimenopausal. 69% of evaluable patients were stage II, 31% stage III, 74% grade 2, 84% ductal carcinoma, mean tumour diameter was 45mm (MRI). CET showed higher rates of febrile neutropenia (11% vs 4%) but lower peripheral neuropathy (3% vs 7%).
Endpoint CET (n=81) CT (n=41) N (%) 95% CI N (%) 95% CI Pathologic stage 0 or 1A at surgery Pre-/perimenopausal Post-menopausal 19 (24%) 16 (31%) 3 (10%) 16-34 20-45 4-26 8 (20%) 6 (24%) 2 (13%) 10-33 12-43 3-36 pCR breast and axilla 6 (7%) 3-16 0 (0%) 0-9 pCR breast only 8 (10%) 5-18 0 (0%) 0-9 ypN0 26 (32%) 22-43 13 (32%) 20-47 RCB 0/1 15 (19%) 12-28 4 (10%) 4-23 Radiological response by MRI 64/81 (79%) 69-87 27/41 (66%) 51-78 Breast conserving surgery 37 (46%) 35-57 21 (51%) 37-67 BCS unsuitable at study entry, to BCS potentially suitable at surgery 26/41 (63%) 48-76 10/24 (42%) 24-61 Underwent successful BCS having been unsuitable for BCS at entry 11/41 (27%) 8/24 (33%)
Conclusions
The primary outcome was not met. ELIMINATE demonstrated a non-significant improvement in down-staging to pathologic stage 0 or 1A in luminal breast cancer with concurrent neoadjuvant chemotherapy and AI therapy. An additional 9% patients receiving CET reached an RCB score < 2 but BCS rates were similar in both groups.
Legal entity responsible for the study
Breast Cancer Trials - Australia and New Zealand.
Funding
Breast Cancer Trials - Australia and New Zealand National Health and Medical Research Council (Australia).
Disclosure
P. Francis: Non-Financial Interests, Personal, Funding, International Lecture Travel: Novartis, Ipsen. N. Zdenkowski: Non-Financial Interests, Personal, Advisory Board: Lilly, Eisai, AstraZeneca; Non-Financial Interests, Personal, Funding, honorarium: Roche, Pfizer, Eisai; Financial Interests, Institutional, Research Grant: Pfizer, Roche, GSK; Financial Interests, Personal, Other, Educational Funding: Roche, Novartis, Amgen. S. Loi: Financial Interests, Institutional, Expert Testimony, Consultant: Aduro Biotech, Puma Biotechnologies, Pfizer, Seattle Genetics, BMS; Financial Interests, Institutional, Advisory Board, Consultant: Novartis, GlaxoSmithKline, Roche Genentech, AstraZeneca, Silverback Therapeutics, G1 Therapeutics; Financial Interests, Institutional, Funding, Research: Novartis, BMS, Merck, Puma Biotechnology, Eli Lilly, Nektar Therapeutics, AstraZeneca, Seattle Genetics, Roche-Genentech; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Seattle Genetics, Novartis, Bristol Myers Squibb, Merck, AstraZeneca, Roche Genentech. J. Lombard: Non-Financial Interests, Personal, Advisory Board: GSK, AstraZeneca. A. Spillane: Non-Financial Interests, Personal, Invited Speaker, Honoraria: Stryker, Lilly; Non-Financial Interests, Personal, Advisory Board: Q-Biotics. All other authors have declared no conflicts of interest.
92MO - Neoadjuvant nivolumab (NIVO) + palbociclib (PALBO) + anastrozole (ANA) for estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2_) primary breast cancer (BC): CheckMate 7A8 (ID 4)
- Sara M. Tolaney (Boston, United States of America)
- Guy Jerusalem (Liège, Belgium)
- Aleix Prat (Barcelona, Spain)
- Roberto F. Salgado (Wilrijk, Belgium)
- Mattea Reinisch (Essen, Germany)
- Cristina Saura Manich (Barcelona, Spain)
- Manuel Ruiz Borrego (Seville, Spain)
- Petros Nikolinakos (Athens, United States of America)
- Jeiry Filian (Princeton, United States of America)
- Felipe Ades (Lawrenceville, United States of America)
- Ning Huang (Princeton, United States of America)
- Antonella Mazzei-Abba (Boudry, Switzerland)
Abstract
Background
Cyclin-dependent kinase (CDK) 4/6 inhibition + ER signaling blockade is a highly effective treatment option for metastatic ER+/HER2− BC. Preclinical studies show evidence of CDK 4/6 and programmed death-1 (PD-1) blockade synergy. CheckMate 7A8, a non-comparative, phase 2 study, evaluated neoadjuvant NIVO + PALBO + ANA in patients (pts) with ER+/HER2− primary BC. Here, we report safety outcomes from the safety run-in phase.
Methods
Eligible pts were men or postmenopausal women with newly diagnosed, histologically confirmed, untreated ER+/HER2− BC with primary tumor ≥ 2 cm, an ECOG performance status of 0/1, and eligible for post-treatment surgery. Pts received NIVO 480 mg IV every 4 wks (1 cycle), PALBO 125 mg (dose level [DL] 1) or 100 mg (DL 2) PO once daily (QD) for 3 wks per cycle, and ANA 1 mg PO QD, for 5 cycles total/until disease progression. Primary endpoint (safety run-in phase) was the number of pts with occurrence of dose-limiting toxicity (treatment-emergent adverse events [AEs] within 4 wks of treatment start).
Results
As of safety data review on 6 May 2021, 21 pts (DL 1: n = 9; DL 2: n = 12) were treated. Most common grade ≥3 treatment-related AEs (TRAEs) were elevated alanine or aspartate aminotransferase, neutropenia, and decreased white blood cell count in DL 1 (n = 2 each; 22.2%), and decreased neutrophil count (n = 5; 41.7%) in DL 2. 5 pts (DL 1) and 4 pts (DL 2) discontinued treatment due to toxicity, mainly grade ≥3 hepatic TRAEs (Table). The study was closed on 27 July 2021 after safety run-in ended. Additional safety and preliminary efficacy data (database lock: 3 February 2022) will be presented.
TRAEs leading to discontinuation, n (%) Dose level 1 (n = 9) Dose level 2 (n = 12) Any grade Grade 3/4 Any grade Grade 3/4 Increased ALT 2 (22.2) 2 (22.2) 1 (8.3) 1 (8.3) Hypertransaminasaemia 0 0 1 (8.3) 1 (8.3) Increased AST 2 (22.2) 2 (22.2) 0 0 Increased transaminases 1 (11.1) 1 (11.1) 0 1 (8.3) Febrile neutropenia 1 (11.1) 1 (11.1) 0 0 Rash 1 (11.1) 1 (11.1) 0 0 Pneumonitis 1 (11.1) 0 1 (8.3) 0
Conclusions
Neoadjuvant NIVO + PALBO + ANA showed a higher incidence of grade ≥3 hepatic TRAEs than historical single-agent safety profiles. These findings show a potential safety risk for the use of endocrine therapy with PD-1 + CDK 4/6 blockade.
Clinical trial identification
NCT04075604.
Editorial acknowledgement
Writing and editorial assistance was provided by Vidya Rajagopalan of Evidence Scientific Solutions, funded by Bristol Myers Squibb.
Legal entity responsible for the study
Bristol Myers Squibb, Princeton, NJ, USA.
Funding
Bristol Myers Squibb, Princeton, NJ, USA.
Disclosure
G. Jerusalem: Financial Interests, Institutional, Research Grant: Novartis, Pfizer; Financial Interests, Institutional, Royalties: Roche; Financial Interests, Personal, Other, Consulting Fees: Novartis, Amgen, Roche, Pfizer, Bristol Myers Squibb, Lilly, AstraZeneca, Daiichi Sankyo, AbbVie; Financial Interests, Personal, Invited Speaker, Honoraria: Novartis, Roche, Amgen, Pfizer, Bristol Myers Squibb, Lilly, AstraZeneca, Seagen; Financial Interests, Personal, Other, Travel/Accommodations/Expenses/Accommodations: Novartis, Roche, Pfizer, Lilly, Amgen; Financial Interests, Personal, Other, Travel/Accommodations/Expense: Bristol Myers Squibb, AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis, Roche, Amgen, Pfizer, Bristol Myers Squibb, Lilly, AstraZeneca, Daiichi Sankyo, AbbVie; Financial Interests, Personal, Other, Medical Writing: Novartis, Roche, Lilly, Amgen, Bristol Myers Squibb, AstraZeneca, MedImmune, Merck. A. Prat: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Other, Honoraria: Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Roche, Amgen, Bristol Myers Squibb, Boehringer, Puma, Oncolytics Biotech, Daiichi Sankyo, AbbVie, AstraZeneca, NanoString Technologies; Financial Interests, Institutional, Sponsor/Funding, Research Funding: Novartis, Roche, Incyte, Puma Biotech; Financial Interests, Personal, Invited Speaker, Honoraria: Roche; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Other, Honoraria: MSD Oncology, Lilly, Daiichi Sankyo, Amgen, Guardant Health; Financial Interests, Personal, Other, Travel/Accommodations/Expense: Daiichi Sankyo. R.F. Salgado: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb; Non-Financial Interests, Personal, Other, Travel/Accommodations: Roche, Puma, Merck. M. Reinisch: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Daiichi Sankyo, Roche, Seagen, Somatex, MSD, Lilly, Pfizer; Financial Interests, Personal, Member, Honoraria: Novartis; Financial Interests, Personal, Advisory Board, Consultancy: Somatex; Financial Interests, Personal, Other, Travel: Pfizer, Novartis. C. Saura: Financial Interests, Personal, Advisory Board: AstraZeneca, AX'Consulting, Byondis B.V., Daiichi Sankyo, Eisai, Exact Sciences, Exeter Pharma, F. Hoffmann, ISSECAM, Medical Statistics Consulting, MediTech, Merck Sharp & Dohme, Novartis, Pfizer, Philips, Pierre Fabre, PintPharma, Puma, Roche Farma, Sanofi-Aventis, Seagen, Zymeworks; Non-Financial Interests, Institutional, Research Grant: Aragon Pharmaceuticals, AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Bristol Myers Squibb, Byondis B.V., Cytomx Therapeutics, Daiichi Sankyo, Eli Lilly and Company, F. Hoffmann-La Roche Ltd., Genentech, German Breast Group Forchungs, GlaxoSmithkline, Immunomedics, Innoup Farma, International Breast Cancer Study Group (IBCSG), Macrogenics, Medica Scientia Innovation Research, Menarini Ricerche, Merck, Merus, Millennium Pharmaceuticals, Novartis, Pfizer, Piqur Therapeutics, Puma, Roche, Sanofi-Aventis, Seattle Genetics, Synthon, Zenith Pharma; Non-Financial Interests, Personal, Member: American Association for Cancer Research (AACR), American Society for Clinical Oncology (ASCO), Geicam (Spanish Breast Cancer Research Group), SOLTI group (Academic research group in breast cancer), Spanish Society of Medical Oncology (SEOM). J. Filian, F. Ades, A. Mazzei-Abba: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. N. Huang: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S.M. Tolaney: Financial Interests, Personal and Institutional, Other, Ad Board Participant/Consultant; Research Funding (to institution): Bristol Myers Squibb, AstraZeneca, Eli Lilly, Merck, Novartis, Seagen, Sanofi, Eisai, Gilead, Pfizer, Genentech/Roche, Odonate; Financial Interests, Institutional, Research Grant: Nektar, NanoString, Exelixis, Cyclacel; Financial Interests, Personal, Advisory Board: Certara, Mersana Therapeutics, G1 Therapeutics, OncoSec, OncoPep, CytomX, Athenex, Ellipses Pharma, 4D Pharma, Puma, Zymeworks, Zentalis, Reveal Genomics, OncXerna, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Chugai Pharma; Financial Interests, Personal, Other, Consultant: Blueprint Medicines. All other authors have declared no conflicts of interest.
Invited Discussant 59MO, 60MO, 91MO and 92MO (ID 5)
Q&A and discussion (ID 457)
93MO - Optimal 18F-FDG PET/CT (FDG-PET) cut-off for pathological complete response (pCR) prediction in HER2-positive [HER2+] early breast cancer (EBC) patients (pts) treated with neoadjuvant trastuzumab (T) and pertuzumab (P) in PHERGain trial (ID 8)
- Géraldine Gebhart (Brussels, Belgium)
- Marleen Keyaerts (Jette, Belgium)
- Thomas Guiot (Brussels, Belgium)
- Patrick Flamen (Brussels, Belgium)
- Manuel Ruiz Borrego (Seville, Spain)
- Agostina Stradella (L'Hospitalet de Llobregat, Spain)
- Begona Bermejo De Las Heras (Valencia, Spain)
- Santiago Escriva de Romani (Barcelona, Spain)
- Lourdes Calvo-Martinez (A Coruña, Spain)
- Nuria Ribelles Entrena (Malaga, Spain)
- Noelia Martinez (Madrid, Spain)
- Cinta Rosa Albacar Miro (Reus, Spain)
- Marco A. Colleoni (Milan, Italy)
- Manuel Atienza de Frutos (Villaviciosa de Odón, Spain)
- Miguel Sampayo-Cordero (Barcelona, Spain)
- Javier Cortes (Madrid and Barcelona, Spain)
- Jose Manuel Perez Garcia (Barcelona, Spain)
- Antonio Llombart Cussac (Valencia, Spain)
Abstract
Background
PHERGain trial investigated the potential of metabolic imaging to identify candidates for chemotherapy (CT) de-escalation in HER2-positive, stage I-IIIA, invasive, operable breast cancer with at least one breast lesion evaluable by FDG-PET. Based on data from NeoALTTO study, FDG-PET “responders” were defined as those pts with maximum standardized uptake value (SUVmax) reduction of at least 40% in all their target lesions after two cycles of T and P. Of the 285 patients included in T+P arm, 227 pts were FDG-PET responders and received a total of 8 cycles of T+P. pCR, defined as pT0/isN0, reached 37.9% (86/227 pts). Here we describe secondary preplanned analysis of the best cut-off of SUVmax reduction for pCR prediction.
Methods
ROC analysis was applied to research the most appropriate deltaSUVmax cut-off in HER2+ EBC pts treated exclusively with neoadjuvant T and P (± endocrine therapy).
Results
The delta SUVmax capability of predicting pCR in terms of AUC was 72.1% (95%CI, 65.1-79.2). The optimal SUVmax reduction cut-off was found to be 77.0%, with a 51.2% sensitivity and a 78.7% specificity for prediction of pCR. Yet, using this cut-off, 32.6% (74/227 pts) would be classified as FDG-PET responders increasing the pCR rate from 37.9% (cut-off ≥40%) to 59.5% (44/74 pts) (p<0.01). With this optimized cut-off 19.4% (44/227 pts) would avoid chemotherapy to achieve a pCR. Subgroup analysis in pts with HER2 immunohistochemistry score 3+ will be reported.
Conclusions
Increased deltaSUVmax cut-off (≥77%) after two cycles of exclusive T+P achieves a pCR rate in the range of control arm with CT+TP in PHERGain (59,5% vs. 57,7%, respectively) selecting a subgroup of pts with HER2 addicted tumors. However, the original cut-off (≥40%) maximizes the number of pts who could avoid CT. The definitive value of pCR in the absence of CT should be confirmed by final DDFS results from PHERGain trial.
Legal entity responsible for the study
Medica Scientia Innovation Research (MEDSIR) Barcelona, Spain and Ridgewood, New Jersey.
Funding
Has not received any funding.
Disclosure
G. Gebhart: Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Funding: Roche. M. Keyaerts: Financial Interests, Institutional, Funding, Precirix; Financial Interests, Personal, Stocks/Shares, Abscint. S. Escriva de Romani: Financial interests, Personal, Invited Speaker: Daiichi Sankyo/AstraZeneca, Pfizer, Roche. Financial interests, Personal, Advisory Board: Daiichi Sankyo/AstraZeneca, Roche, Seagen. Financial interests, Insitutional, Other, Local PI: Byondis, Lilly, MedSIR, Roche, Synthon. M.A. Colleoni: Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Role: Pfizer, OBI Pharma, Celldex; AstraZeneca; Financial Interest, Personal, Research Grant: Roche. M. Atienza de Frutos: Financial Interests, Personal, Full or part-time Employment: Lilly; Financial Interests, Personal, Stocks/Shares: Lilly. M. Sampayo-Cordero: Financial Interests, Personal, Other: MEDSIR, Syntax for Science, Nestle; Financial Interests, Personal, Advisory Board: MEDSIR, Syntax for Science, Nestle; Financial Interests, Personal, Speaker’s Bureau: MEDSIR, Syntax for Science, Nestle, Roche; Financial Interests, Personal, Funding: MEDSIR, Syntax for Science, Nestle, Roche. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp & Dohme, GSK, LEUKO, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Zymeworks, Gemoab, Gilead, Menarini, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Baxalta GMBH/Servier Affaires, Roche, Ariad Pharmaceuticals, AstraZeneca, Bayer Healthcare, Eisai, Guardanth Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo. J.M. Perez Garcia: Financial Interests, Personal, Advisory Board: Roche, Eli Lilly; Financial Interests, Personal, Expert Testimony: Eisai. A. Llombart Cussac: Financial Interests, Personal, Leadership Role: Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, MSD; Financial Interests, Personal, Stocks/Shares: MEDSIR, Initia-Research; Financial Interests, Personal, Advisory Board: Lilly, Roche, Pfizer, Novartis, Pierre Fabre, Genomic Health, GSK; Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, MSD; Financial Interests, Institutional, Funding: Roche, Foundation Medicine, Pierre Fabre, Agendia; Financial Interests, Personal, Other: Roche, Lilly, Novartis, Pfizer, AstraZeneca. All other authors have declared no conflicts of interest.