Miguel Martin Jimenez (Madrid, Spain)
Hospital General Universitario Gregorio MarañonAuthor Of 11 Presentations
Gene-expression signature for treatment decision-making: Who to test? Which signature? (ID 426)
Patient case study: how does local clinical practice vary for patients with brain metastases? (ID 368)
Consistency of approach: how can we personalise and adapt treatment sequencing for patients with HER2-positive MBC? (ID 371)
Patient case study: how does treatment sequencing vary in local clinical practice across Europe for HER2-positive MBC? (ID 367)
Which local factors influence treatment sequencing for HER2-positive MBC? (ID 370)
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.
62P - Outcomes of high-risk breast cancer (BC) patients from El Álamo IV registry and GEICAM adjuvant clinical trials (ID 77)
- Miguel Martin Jimenez (Madrid, Spain)
- Alvaro Rodríguez-Lescure (Elche, Spain)
- Raquel Andres Conejero (Zaragoza, Spain)
- Sonia Servitja Tormo (Barcelona, Spain)
- Antonio Anton Torres (Zaragoza, Spain)
- Manuel Ruiz Borrego (Seville, Spain)
- Begona Bermejo De Las Heras (Valencia, Spain)
- Angel Guerrero (Valencia, Spain)
- Manuel Ramos Vazquez (A Coruña, Spain)
- Ana Santaballa Bertran (Valencia, Spain)
- Montserrat Munoz (Barcelona, Spain)
- J. Norberto Batista (San Cristobal de la Laguna, Spain)
- Sara Lopez-Tarruella Cobo (Madrid, Spain)
- J. Ignacio Chacon Lopez-Muniz (Toledo, Spain)
- Isabel Alvarez Lopez (San Sebastian (Donostia), Spain)
- Maria P. Martinez del Prado (Bilbao, Spain)
- Juan Jose Miralles (San Sebastian de los Reyes, Spain)
- Oscar Polonio (San Sebastian de los Reyes, Spain)
- Carlos Jara Sanchez (Alcorcon, Spain)
- Marta Mori de Santiago (Las Palmas de Gran Canaria, Spain)
Abstract
Background
Chemotherapy (CT) followed by endocrine therapy (ET) is the current standard of care for high-risk hormone receptor (HR)-positive/HER2-negative early breast cancer (EBC). The monarchE, with 27-months follow-up, showed that the addition of abemaciclib for 2 years in combination with ET improves the 3-years invasive relapse rate (IRR) and distant relapse rate (DRR) for patients (pts) with high-risk EBC. Obtaining data on the long-term risk of relapse is needed to put into context the magnitude of abemaciclib benefit.
Methods
We performed a retrospective analysis of 1742 HR-positive/HER2-negative EBC pts fulfilling the high-risk criteria of the monarchE in order to estimate their long-term outcomes. They were selected from El Álamo IV registry with pts diagnosed between 2002 and 2005 and 3 adjuvant GEICAM studies (9906, 2003-10 and 2006-10,) carried out from 1999 to 2010. Pts were divided in 2 cohorts (C), similarly to monarchE: C1) ≥ 4 positive axillary lymph nodes (PALN) or 1–3 PALN with tumor size (T) ≥ 5cm and/or histologic grade (G) 3and C2) 1–3 PALN (with T < 5cm and G < 3) and Ki-67 ≥ 20%. Pts had to have undergone surgery with curative intent and had received adjuvant CT (anthracyclines +/- taxanes) and ET.
Results
El Álamo IV registered 6374 luminal EBC pts from which 16.2% were high-risk and included in the analysis (n=1030; 981 C1, 49 C2). In addition 326 pts from 9906 (311 C1, 15 C2), 225 pts from 2003-10 (C1) and 161 pts from 2006-10 (C1) were included. With a median follow-up of 10.2 years, the IRR and DRR at 5 and 10 years were 22% and 34.8% and 19.7% and 31.0%, respectively. Per-year IRR, DRR, and death rate (DR) are described in the table. IRR and DRR increased from year 2, till year 3 followed by a second peak at years 7-8. DR increased steadily from year 1 (7.8% and 24.8% at 5 and 10 years).
Global (n=1742 pts) Times in years 1 2 3 4 5 6 7 8 9 10 IRR (%) Total 2.88 5.66 6.11 5.37 4.48 4.21 4.28 4.44 3.91 3.31 C1 2.93 5.51 6.14 5.43 4.5 4.29 4.27 4.61 3.85 3.44 C2 1.59 9.84 5.45 3.85 4 2.08 4.55 0 5.13 0 DRR (%) Total 2.70 5.23 5.44 4.57 3.83 3.65 3.83 3.22 3.64 2.64 C1 2.74 5.12 5.58 4.6 3.83 3.72 3.81 3.35 3.59 2.75 C2 1.59 8.2 1.79 3.64 3.77 1.96 4.26 0 4.76 0 DR (%) Total 0.58 1.69 2.44 3.25 3.51 3.47 4.13 4.20 4.43 4.19 C1 0.48 1.69 2.47 3.37 3.45 3.54 4.21 4.2 4.43 4.07 C2 3.13 1.61 1.64 0 5.08 1.79 1.92 4.08 4.35 6.98
Conclusions
The highest yearly risk of recurrence of high-risk EBC, defined as in monarchE, is at 3 years after diagnosis but remains high in the long-term follow-up.
Legal entity responsible for the study
GEICAM Spanish Breast Cancer Group.
Funding
LILLY.
Disclosure
M. Martin Jimenez: Financial Interests, Personal, Advisory Board: ASTRAZENECA; Financial Interests, Personal, Invited Speaker: PFIZER; Financial Interests, Personal, Invited Speaker: ASTRAZENECA; Financial Interests, Personal, Advisory Board: LILLY; Financial Interests, Personal, Invited Speaker: LILLY; Financial Interests, Personal, Invited Speaker: NOVARTIS; Financial Interests, Personal, Advisory Board: ROCHE/GENENTECH; Financial Interests, Personal, Invited Speaker: ROCHE/GENENTECH; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: NOVARTIS; Financial Interests, Institutional, Research Grant: ROCHE; Financial Interests, Institutional, Research Grant: Puma; Non-Financial Interests, Invited Speaker: TRIO; Non-Financial Interests, Leadership Role: GEICAM. B. Bermejo De Las Heras: Financial Interests, Institutional, Advisory Role: MSD, Roche, Pierre Fabre, Novartis, AstraZeneca, Seagen; Financial Interests, Institutional, Speaker’s Bureau: Pfizer, Roche, MSD, Palex, Eisai, Daiichi, AstraZeneca, Seagen. A. Guerrero: Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Advisory Board: Pfizer, Palex, Novartis, AstraZeneca, Pierre Fabre; Financial Interests, Personal, Other, Travel grant: Pfizer, Novartis; Financial Interests, Institutional, Speaker’s Bureau: Novartis, Pfizer, Lilly, AstraZeneca. A. Santaballa Bertran: Financial Interests, Institutional, Advisory Role: Pfizer. S. Lopez-Tarruella Cobo: Financial Interests, Institutional, Advisory Role: AstraZeneca, Novartis, Roche, Pfizer, Pierre Fabre, Lilly, Seagen, Daiichi Sankyo Europe GmbH, Gilead Sciences,MSD, GalaxoSmithkline, Veracyte; Financial Interests, Personal, Speaker’s Bureau: Lilly. All other authors have declared no conflicts of interest.
85P - Correlation between Prosigna® and three IHC-based surrogate intrinsic breast cancer subtype classifiers: a real world-study (ID 99)
- Miguel Martin Jimenez (Madrid, Spain)
- María Del Monte (Madrid, Spain)
- Yolanda Jerez (Madrid, Spain)
- Isabel Echavarria Diaz-Guardamino (Madrid, Spain)
- Blanca Herrero Lopez (Madrid, Spain)
- Salvador Gamez Casado (Madrid, Spain)
- Marta Roche-Molina (Madrid, Spain)
- Ivan Marquez-Rodas (Madrid, Spain)
- María Cebollero (Madrid, Spain)
- Enrique Alvarez (Madrid, Spain)
- Tatiana Massarrah (Madrid, Spain)
- Inmaculada Ocaña (Madrid, Spain)
- Ainhoa Arias (Madrid, Spain)
- Jose Angel Garcia Saenz (Madrid, Spain)
- Fernando Moreno Anton (Madrid, Spain)
- Clara Olier Garate (Alcorcon, Spain)
- Diana Moreno Muñoz (Alcorcon, Spain)
- David Marrupe Gonzalez (Mostoles, Spain)
- Tomás Merina (Madrid, Spain)
- Sara Lopez-Tarruella Cobo (Madrid, Spain)
Abstract
Background
The intrinsic subtype classification provides prognostic information on the outcome of patients with hormone receptor-positive/HER2-negative (HR+/HER2-) early breast cancer. The nCOUNTER PAM-50 test is the mRNA-based technique approved for the identification of Luminal (Lum) A and LumB tumors, to select candidates for additional adjuvant chemotherapy, mainly those with LumB tumors. Since genomic tests are expensive and not widely available, some IHC-based surrogated classifiers have been proposed based on HR, HER2 and Ki67 expression. In this real-world data analysis, we determine the ability of three different surrogate classifiers to predict the real nCOUNTER PAM-50 subtype.
Methods
Tumor samples centralized to perform the nCOUNTER PAM-50 assay in the Laboratory of Traslational Oncology at the Hospital General Universitario Gregorio Marañon between 2014 and 2020 were included in the analysis. HR and Ki67 status were determined at local laboratories. All tumors were HER2 negative by local standards. Correlation among nCOUNTER PAM-50 test and three classifiers are analysed (Cheang M et al., J Natl Cancer Inst 2009; Prat A et al., J Clin Oncol 2013; Maisonneuve P et al., Breast Cancer Res. 2014).
Results
A total of 1105 samples were analysed. 55 out of them did not have Ki67 value reported, being excluded from the analysis. From the remaining 1050 samples, 679 (64.6%) were classified as LumA and 351 (33.4%) as LumB. Concordance among these molecular subtypes by nCOUNTER PAM-50 assay and the IHC surrogated are summarized in the table. The classification based on Maisonneuve et al. 2014 showed the best correlation, although the correlation was only fair.
Prosigna kappa Lum A Lum B Cheang Lum A n=456 % 391 65 0,3397 Lum B n=573 % 287 286 Prat Lum A n=345 % 300 45 0,271 Lum B n=640 % 348 292 Maisonneuve Lum A n=607 % 490 117 0,4214 Lum B n=578 % 106 172
Conclusions
In this study, the concordance between Lum subtypes determined by 3 different IHC-based classifiers and nCOUNTER PAM-50 assay is clearly suboptimal. Between 13 - 19% of nCOUNTER PAM-50 LumB tumors were classified as LumA by IHC and could be undertreated. Conversely, between 38-54% of nCOUNTER PAM-50 LumA tumors were classified as LumB by IHC and could receive unnecessary chemotherapy.
Legal entity responsible for the study
Miguel Martín Jiménez.
Funding
Has not received any funding.
Disclosure
M. Martin Jimenez: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Astrazeneca; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Roche/Genentech; Financial Interests, Personal, Invited Speaker: Roche/Genentech; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Puma; Non-Financial Interests, Invited Speaker: Trio; Non-Financial Interests, Leadership Role: GEICAM. Y. Jerez: Financial Interests, Personal, Advisory Role: Novartis, Pfizer, Roche and AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche, Novartis and AstraZeneca; Financial Interests, Personal, Training: Roche, Novertis, Pfizer and Teva. I. Echavarria Diaz-Guardamino: Financial Interests, Personal, Invited Speaker: Eli Lilly, Pfizer, Roche, Novartis and Teva; Financial Interests, Personal, Advisory Role: Eli Lilly, Pfizer, Roche, Novartis and Teva. I. Marquez-Rodas: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Highligth Therapeutics; Financial Interests, Personal, Advisory Board: Bioline Rx; Financial Interests, Personal and Institutional, Invited Speaker, GEM1802 clinical trial: Pierre Fabre; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: Novartis; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: BMS; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: Roche; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: Pierre Fabre; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: Incyte; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: MSD; Financial Interests, Institutional, Invited Speaker, National coordinator of Spotlight 203 clinical trial: Highlight Therapeutics; Non-Financial Interests, Invited Speaker: Spanish Melanoma Group. T. Massarrah: Financial Interests, Personal, Advisory Role: AstraZeneca, Novartis, Roche; Financial Interests, Personal, Training: Novartis, AstraZeneca. J.Á. García Saenz: Financial Interests, Personal, Advisory Role: Seagen, Gilead, Sanofi; Financial Interests, Personal, Invited Speaker: Novartis, Celgene, Eli Lilly, Eisai, AstraZeneca, Daiichi Sankyo, MSD. F. Moreno Anton: Financial Interests, Personal, Invited Speaker: Novartis, Roche, Pfizer, AstraZeneca, Diachi-Sankyo, Exact Sciences, Fresenius Kabi Institution research from Pfizer; Financial Interests, Personal, Training: Novartis, Roche, Pfizer. C. Olier Garate: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer; Financial Interests, Personal, Advisory Role: Novartis, Pfizer. D. Moreno Muñoz: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer; Financial Interests, Personal, Advisory Role: Novartis, Pfizer. T. Merina: Financial Interests, Personal, Other: Oncogenomics. S. Lopez-Tarruella Cobo: Financial Interests, Personal, Advisory Role: Novartis, Pierre Fabre, Pfizer, Roche, AstraZeneca, Daiichi Sankyo, MSD, Seagen, GlaxoSmithKline, Gilead, Veracyte and Lilly; Financial Interests, Personal, Invited Speaker: Novartis, Roche, Lilly. All other authors have declared no conflicts of interest.
162O - Primary analysis from DS8201-A-U105: A 2-part, open label, phase 1b trial assessing trastuzumab deruxtecan (T-DXd) with nivolumab (nivo) in patients (pts) with HER2-expressing advanced breast cancer (ID 304)
- Erika P. Hamilton (Nashville, United States of America)
- Charles L. Shapiro (New York, United States of America)
- Valentina Boni (Madrid, Spain)
- Miguel Martin Jimenez (Madrid, Spain)
- Gianluca Del Conte (Milan, Italy)
- Javier Cortes (Madrid and Barcelona, Spain)
- LAILA Agrawal (Louisville, United States of America)
- Hendrik-Tobias Arkenau (London, United Kingdom)
- Antoinette R. Tan (Charlotte, United States of America)
- Philip R. Debruyne (Cambridge, United Kingdom)
- Anna R. Minchom (London, United Kingdom)
- Annemie Rutten (Wilrijk, Belgium)
- Frances Valdes-Albini (Miami, United States of America)
- Evan Yu (Seattle, United States of America)
- Fumitaka Suto (Basking Ridge, United States of America)
- Fu-Chih Cheng (Basking Ridge, United States of America)
- Bincy Augustine (Basking Ridge, United States of America)
- Ben Cheng (Basking Ridge, United States of America)
- Daniel Barrios (Basking Ridge, United States of America)
- Sara A. Hurvitz (Los Angeles, United States of America)
Abstract
Background
In DESTINY-Breast01 (NCT03248492), T-DXd showed efficacy and safety in pts with HER2+ metastatic breast cancer (MBC) with prior T-DM1. Preclinical models showed that T-DXd combined with an anti–PD-1 antibody had greater efficacy vs either agent alone (Iwata Mol Cancer Ther 2018). This was a 2-part, open-label, multicenter, phase 1b study of T-DXd with nivo in pts with HER2-expressing MBC or advanced urothelial cancer (NCT03523572). Primary results from part 2 for MBC pts are reported.
Methods
Pts were immunotherapy naive with centrally confirmed HER2+ (IHC 3+ or IHC 2+/ISH+) MBC after T-DM1 or HER2 low (IHC 1+ or IHC 2+/ISH-) MBC after standard-of-care. Pts received the recommended dose for expansion T-DXd 5.4 mg/kg and nivo 360 mg IV Q3W. The primary endpoint was confirmed ORR (cORR) assessed by independent central review (ICR) per RECIST v1.1. Secondary endpoints included progression-free survival (PFS), duration of response (DOR), and safety.
Results
At the primary analysis data cutoff (July 22, 2021), 48 pts (HER2+, n = 32; HER2 low, n = 16) received T-DXd and nivo. Median follow-up duration was 18.7 mo for HER2+ pts and 12.7 mo for HER2-low pts. The cORR by ICR was 65.6% (95% CI, 46.8-81.4) and 50% (95% CI, 24.7-75.3); median PFS was 11.6 mo (95% CI, 6.9-NE) and 7.0 mo (95% CI, 2.3-10.8); and median DOR was NE (95% CI, 7.9-NE) and 5.5 mo (95% CI, 2.8-8.0) for HER2+ and HER2 low pts, respectively. Overall, median treatment duration was 7.9 mo for T-DXd and 5.8 mo for nivo. In parts 1 and 2 (T-DXd 5.4 mg/kg, nivo 360 mg; n = 48), TEAEs grade ≥3 occurred in 50.0% of pts; nausea (56.3%) was the most common any-grade TEAE; and 7 (14.6%) HER2+ pts had adjudicated drug-related interstitial lung disease (6 grade 2; 1 grade 5).
Conclusions
Results of T-DXd plus nivo show antitumor activity consistent with previously reported data for T-DXd monotherapy in HER2+ BC, with no discernable benefit with the addition of nivo in this late-line setting. Data from the small HER2-low cohort are insufficient to determine the effects of PD-1/PD-L1 combination therapy. The combination safety profile was similar to that of each study drug as monotherapy.
Clinical trial identification
NCT03523572.
Editorial acknowledgement
Under the guidance of authors, assistance in medical writing and editorial support was provided by Jill Seabrook, PhD, of ApotheCom, and was funded by Daiichi Sankyo, Inc.
Legal entity responsible for the study
Daiichi Sankyo, Inc. and AstraZeneca.
Funding
Daiichi Sankyo, Inc. and AstraZeneca.
Disclosure
E.P. Hamilton: Financial Interests, Institutional, Advisory Board: Arcus, Arvinas, Black Diamond, Boehringer Ingelheim, CytomX, Daiichi Sankyo, Dantari, Deciphera Pharmaceuticals, Eisai, H3 Biomedicine, iTeos, Janssen, Lilly, Loxo, Merck, Mersana, Novartis, Pfizer, Puma Biotechnology, Relay Therapeutics, Roche/Genentech; Financial Interests, Institutional, Research Grant: AbbVie, Acerta Pharma, ADC Therapeutics, AKESOBIO Australia, Amgen, Aravive, 3 ArQule, Arvinas, AstraZeneca, AtlasMedx, Black Diamond, Boehringer Ingelheim, Clovis, Compugen, Curis, CytomX, Daiichi Sankyo, Dana Farber Cancer Inst., Deciphera, eFFECTOR The. C.L. Shapiro: Financial Interests, Personal, Other, Honoraria: UF Breast Symposium; Financial Interests, Personal, Advisory Board: 2nd MD, Anthenum, Gilead; Financial Interests, Personal, Other, Royalties: UptoDate. V. Boni: Financial Interests, Personal, Other, Honoraria: Director of Clinical Cancer Research, NEXT Madrid, Universitary Hospital QuirónSalud Pozuelo; Financial Interests, Institutional, Other, Honoraria: AbbVie; ACEO; Adaptaimmune; Amcure; Amgen; AstraZeneca; BMS Cytomx; GSK; Genentech/Roche; H3; Incyte; Janssen; Kura; Lilly; Loxo; Nektar; Macrogenics; Menarini; Merck; Merus; Nanobiotix; Novartis; Pfizer; PharmaMar; Principia; Puma; Sanofi; Taiho; Tesaro; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Ideaya Biosciences; Loxo Therapeutics, CytomX Therapeutics; Guidepoint; Oncoart; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly. M. Martin Jimenez: Financial Interests, Personal, Other, Honoraria: Roche, Novartis, Daiichi Sankyo, Seagen, AstraZeneca, Pfizer, Lilly; Financial Interests, Personal, Advisory Board: Roche, Novartis, Daiichi Sankyo, Seagen, AstraZeneca, Pfizer, Lilly; Financial Interests, Institutional, Research Grant: Roche, Puma, Novartis. G. Del Conte: Financial Interests, Personal, Advisory Board: Novartis, BMS; Financial Interests, Personal, Other, Travel Expenses: Janssen, Astellas, Pfizer. J. Cortés: Financial Interests, Personal, Other, Honoraria: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo; 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, Gemoab, Gilead, Menarini, Zymework; Financial Interests, Personal, Stocks/Shares: MedSIR; Financial Interests, Institutional, Research Grant: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman- La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo, AstraZeneca. L. Agrawal: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Immunomedics, Breast Cancer Index; Financial Interests, Personal, Speaker’s Bureau: Lilly. H. Arkenau: Financial Interests, Personal, Advisory Board: Roche, LabGenius, Cell Centric, Daiichi Sankyo, Bicycle Therapeutics; Guardant Health, BioNTech, Bayer, Beigene, Servier; Financial Interests, Personal, Other, Honoraria: Bicycle Therapeutics, BioNTech, Bayer, Beigene, Servier, Roche and Guardant Health; Financial Interests, Personal, Other, Travel Expenses: Amgen; Financial Interests, Personal, Full or part-time Employment: Sarah Cannon. A.R. Tan: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Institutional, Research Grant: Daiichi Sankyo. P.R. Debruyne: Financial Interests, Personal, Other, Honoraria: BMS, Merck/Pfizer, MSD, Roche, Bayer; Financial Interests, Personal, Stocks/Shares: Alkermes; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen. A.R. Minchom: Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceuticals, Novartis Oncology, Faron Pharmaceuticals, Bayer Pharmaceuticals; Financial Interests, Personal, Advisory Board: Janssen Pharmaceuticals, Merck Pharmaceuticals, Takeda Pharmaceuticals and Genmab Pharmaceuticals; Financial Interests, Personal, Other, Travel Expenses: Amgen Pharmaceuticals and LOXO Oncology. E. Yu: Financial Interests, Personal, Advisory Board: Advanced Accelerator Applications, Bayer, Janssen, Merck, Exelus, Clovis, AbbVie, Sanofi; Financial Interests, Invited Speaker: Daiichi Sankyo, Dendreon, Taiho, Merck, Seagen, Blue Earth, Bayer, Lantheus. F. Suto, F. Cheng, B. Augustine, B. Cheng, D. Barrios: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc. S.A. Hurvitz: Financial Interests, Institutional, Research Grant: Ambrx, Amgen, AstraZeneca, Arvinas, Bayer, Cytomx, Daiichi Sankyo, Dignitana, Genentech/Roche, Gilead, GSK, Immunomedics, Eli Lilly, Macrogenics, Novartis, Pfizer, OBI Pharma, Orinove, Pieris, Puma, Radius, Sanofi, Seattle Genetics/Seagen, Zymeworks, Pho; Financial Interests, Personal, Principal Investigator: Novartis, Daiichi Sankyo, Seagen, GNE/Roche; Financial Interests, Personal, Advisory Board: Novartis, Lilly, Daiichi Sankyo/AZ, GNE/Roche, Sanofi; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Lilly; Non-Financial Interests, Personal, Other, Uncompensated consulting/ad boards: 4DPharma, Ambrx, Amgen, Artios, Arvinas, Daiichi Sankyo, Dantari, Genentech/Roche, Immunomedics, Macrogenics, Eli Lilly, Novartis, NK Max, Pieris, Pyxis, Seagen, Biotheranostics. All other authors have declared no conflicts of interest.
207TiP - Phase 3 study of tucatinib or placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer (HER2CLIMB-05, trial in progress) (ID 215)
- Veronique Dieras (Rennes, France)
- Miguel Martin Jimenez (Madrid, Spain)
- Ciara C. O'Sullivan (Rochester, United States of America)
- Joohyuk Sohn (Seoul, Korea, Republic of)
- KONSTANTINOS TRYFONIDIS (North Wales, United States of America)
- Libero Santarpia (Bothell, United States of America)
- Shan Yang (Bothell, United States of America)
- Erika P. Hamilton (Nashville, United States of America)
Abstract
Background
The current first-line (1L) standard of care (SOC) for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) is trastuzumab (T) plus pertuzumab (P) and a taxane. Despite advances in 1L SOC, most patients (pts) progress during maintenance therapy with T+P. Tucatinib is a tyrosine kinase inhibitor (TKI) approved in combination with T and capecitabine for adults with HER2+ MBC, with and without brain metastases (BM). In HER2CLIMB, the addition of tucatinib significantly prolonged progression-free survival (PFS) and overall survival (OS) in pts with HER2+ MBC and was well tolerated. Adding tucatinib also reduced the risk of disease progression or death in pts with untreated and/or active BM (Murthy et al. 2020, Curigliano et al. 2021). HER2CLIMB-05 investigates whether adding tucatinib to 1L SOC as maintenance therapy will extend PFS while maintaining quality of life (QOL).
Trial design
HER2CLIMB-05 (NCT05132582) is a phase 3, randomized, double-blind study evaluating tucatinib plus T+P as maintenance therapy for HER2+ MBC. Approximately 650 pts will be enrolled. Eligible pts will have advanced HER2+ disease, no progression on 4–8 cycles of prior 1L SOC, ECOG Performance Status of 0 or 1, and no or asymptomatic BM. Exclusion criteria include prior treatment with anti-HER2 and/or anti-epidermal growth factor receptor TKI (prior SOC for early BC is permitted) or inability to undergo contrast magnetic resonance imaging of the brain. Pts will be randomized 1:1 to receive either tucatinib or placebo twice daily, with T+P once every 21 days. Pts with HR+ disease may receive endocrine therapy. The primary endpoint is investigator-assessed PFS. Secondary endpoints include OS (key endpoint), time to deterioration of health-related QOL, central nervous system PFS, safety, and pharmacokinetic (PK) parameters. PFS and OS will be compared using a 2-sided stratified log-rank test between treatment groups. Time-to-event endpoints will be summarized using the Kaplan–Meier method. PK and safety data will be summarized using descriptive statistics. Enrollment is ongoing in the US, with additional sites planned.
Clinical trial identification
NCT05132582.
Legal entity responsible for the study
Seagen Inc.
Funding
Seagen Inc.
Disclosure
V.C. Dieras: Financial Interests, Personal, Other, Travel Expenses: Roche, Novartis, Pfizer, Lilly, AstraZeneca, Daiichi Sankyo, Seagen, Gilead; Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: Roche/Genentech, Novartis, Lilly, Pfizer, AstraZeneca, AbbVie, MSD, Daiichi Sankyo, Seagen, Gilead, Eisai, Pierre Fabre Oncologie; Financial Interests, Personal, Other, Symposia: Roche, Novartis, Pfizer, Lilly, AstraZeneca, Daiichi Sankyo, Seagen, Gilead. M. Martin Jimenez: Financial Interests, Personal, Advisory Board: Roche, Lilly, Novartis, Pierre Fabre, Pfizer, Daiichi Sankyo, Seagen; Financial Interests, Personal, Other, Honoraria: Roche, Lilly, Novartis, Pierre Fabre, Pfizer, Daiichi Sankyo, Seagen; Financial Interests, Personal, Funding, Research Funding/Grants: Puma, Roche, Novartis. C.C.M. O'Sullivan: Financial Interests, Personal, Full or part-time Employment: Mayo Clinic Rochester; Financial Interests, Personal, Funding, Research Funding/Grants: Lilly, Seattle Genetics, Bavarian Nordic, Minnemarita Therapeutics, Biovica. J. Sohn: Financial Interests, Personal, Funding: Seagen Inc. K. Tryfonidis: Financial Interests, Personal, Full or part-time Employment: Merck. L. Santarpia, S. Yang: Financial Interests, Personal, Full or part-time Employment: Seagen Inc. E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Boehringer Ingelheim, Novartis, Dantari, Lilly, Merck, Puma Biotechnology, Silverback Therapeutics, CytomX, Pfizer, Mersana, Black Diamond, H3 Biomedicine, Daiichi Sankyo, AstraZeneca, Arvinas, Deciphera Pharmaceuticals, Eisai, Seagen, Arcus, iTeos, Janssen, Loxo, Relay Therapeutics; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Silverback Therapeutics, Millenium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Fochon, Molecular Templates, Onconova Therapeutics, Dana Farber Cancer Hospital, Hutchinson MediPharma, MedImmune, Seagen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, AbbVie, Nucana, Orinove, Leap Therapeutics, Zenith Epigenetics, Harpoon, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, Merck, PharmaMar, Olema, Immunogen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Atlas MedX, Ellipses, Incyte, Jacobio, Mabspace Biosciences, Myraid Genetic Labs, ORIC Pharmaceuticals, Pieris Pharmaceuticals; Financial Interests, Institutional: Pionyr Immunotherapeutics.
LBA4 - Updated overall survival (OS) results from the first-line (1L) population in the Phase III MONALEESA-3 trial of postmenopausal patients (pts) with HR+/HER2? advanced breast cancer (ABC) treated with ribociclib (RIB) + fulvestrant (FUL) (ID 12)
- Patrick Neven (Leuven, Belgium)
- Peter A. Fasching (Erlangen, Germany)
- Stephen Chia (Vancouver, Canada)
- Guy Jerusalem (Liège, Belgium)
- Seock-Ah Im (Seoul, Korea, Republic of)
- Katarina Petrakova (Brno, Czech Republic)
- Giulia V. Bianchi (Milan, Italy)
- Miguel Martin Jimenez (Madrid, Spain)
- Arnd Nusch (Velbert, Germany)
- Gabe S. Sonke (Amsterdam, Netherlands)
- Luis De la Cruz Merino (Seville, Spain)
- J. T. Beck (Springdale, United States of America)
- Juan Pablo Zarate (Algiers, Algeria)
- Yongyu Wang (Florham Park, United States of America)
- Arunava Chakravartty (East Hanover, United States of America)
- Craig Wang (Basel, Swaziland)
- Dennis Slamon (Los Angeles, United States of America)
Abstract
Background
The MONALEESA-3 (NCT02422615) final protocol-specified OS analysis and an exploratory OS analysis with extended follow-up demonstrated significant OS benefit with RIB + FUL vs placebo (PBO) + FUL as 1L or second-line (2L) treatment (tx). At the time of these analyses, the median (m) OS was 53.7 vs 41.5 mo for RIB vs PBO in the intent-to-treat (ITT) population. Although the mOS was not reached in the RIB arm for 1L pts, the mOS in 2L pts was 39.7 vs 33.7 mo for RIB vs PBO. We report an exploratory analysis of OS with additional follow-up, allowing further characterization of long-term OS benefits of RIB in the 1L setting.
Methods
Postmenopausal pts with HR+/HER2− ABC were randomized 2:1 to receive RIB + FUL or PBO + FUL. Updated OS in the 1L setting (pts with de novo disease or relapse >12 mo from completion of [neo]adjuvant endocrine therapy) was assessed by Cox proportional hazards model and Kaplan-Meier methods. Progression-free survival 2 (PFS2) and chemotherapy-free survival (CFS) were also evaluated.
Results
At the data cutoff (January 12, 2022), the median follow-up for 1L pts was 70.8 mo; 16.5% and 8.6% of pts remained on tx in the RIB and PBO arms, respectively. An OS benefit was observed with 1L RIB vs PBO (mOS, 67.6 vs 51.8 mo; HR, 0.67; 95% CI, 0.50-0.90). The OS rate at 5 years was 56.5% vs 42.1% for RIB vs PBO, respectively. PFS2 (HR, 0.64) and CFS (HR, 0.62) favored RIB vs PBO. In pts who discontinued study tx, 81.8% and 89.7% received subsequent antineoplastic therapy, while 16.7% vs 35.0% received a subsequent cyclin-dependent kinase 4/6 inhibitor in the RIB vs PBO arms. Results in the ITT and 2L populations were generally consistent with the previous analysis.
Conclusions
This exploratory analysis of 1L RIB + FUL in MONALEESA-3 reports the longest mOS thus far (67.6 mo—a 15.8-mo improvement vs PBO and a relative reduction in risk of death of 33%) in a 1L population in a Phase III clinical trial in ABC. These impressive results in the 1L setting further support the use of RIB + ET in HR+/HER2− ABC.
Clinical trial identification
NCT02422615.
Editorial acknowledgement
Medical writing support was provided by Casey Nielsen at MediTech Media, funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
P.A. Fasching: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Seagen, Roche, Gilead; Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, Seagen, Roche, Hexal, Agendia, Sanofi Aventis, Gilead; Financial Interests, Institutional, Funding, Institutional Funding: Biontech, Cepheid; Financial Interests, Personal, Research Grant: Pfizer. S. Chia: Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Hoffman La Roche, Eli Lilly; Financial Interests, Institutional, Funding, My institution received funds for participation in clinical trials by: Novartis, Pfizer, Hoffman La Roche, Eli Lilly. G. Jerusalem: Financial Interests, Personal, Other, Grants, Personal Fees & Non-Financial Support: Novartis, Roche, Pfizer; Financial Interests, Personal, Other, Personal Fees & Non-Financial Support: Lilly, Amgen, BMS, AstraZeneca; Financial Interests, Personal, Other, Personal Fees: AbbVie, Daiichi Sankyo, Seagen; Non-Financial Interests, Personal, Other, Non-Financial Support: Medimmune, Merck KGaA. M. De Laurentiis: Financial Interests, Personal, Speaker’s Bureau, Speaker's Honoraria: Pfizer, Novartis, Roche, AstraZeneca, Eisai, Eli Lilly, Pierre Fabre; Financial Interests, Personal, Advisory Board, Advisory Board Honoraria: Pfizer, Novartis, Roche, AstraZeneca, Eisai, Eli Lilly, MSD, Pierre Fabre. S. Im: Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca, Hanmi, Pfizer, Novartis; Non-Financial Interests, Personal, Other, Travel support: Novartis; Financial Interests, Personal, Advisory Role, Participation in advisory meetings: Eisai, Amgen, Roche, Lilly, GSK, MSD; Financial Interests, Personal, Other: Daewoong Pharm. K. Petrakova: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Roche, Pfizer. G.V. Bianchi: Financial Interests, Personal, Advisory Role: Roche, Eli Lilly, Novartis, Seagen, AstraZeneca/Daichi Sankyo, MSD. M. Martin Jimenez: Financial Interests, Personal, Speaker’s Bureau, Speaker Honoraria: Lilly, Pfizer; Financial Interests, Personal, Advisory Board, Honoraria for Participation in Advisory Boards: Lilly, Pfizer, AstraZeneca, Novartis, Roche-Genentech, GlaxoSmithKline, PharmaMar, Taiho Oncology; Financial Interests, Personal, Research Grant: Novartis, Roche-Genentech. A. Nusch: Financial Interests, Personal, Advisory Role, Consulting/Advisory role: Novartis, Amgen; Financial Interests, Personal, Funding, Research Funding: Novartis; Other, Personal, Travel/Accommodation/Expenses: Novartis; G.S. Sonke: Financial Interests, Institutional, Other, Institutional Reimbursement for Patient Accrual: Novartis; Financial Interests, Institutional, Other, Institutional Reimbursement for Education and Steering Committee Activities: Novartis; Financial Interests, Institutional, Other, Institutional research support: Merck, AstraZeneca, Roche. J.T. Beck: Financial Interests, Institutional, Research Grant, Institutional funding for doing research: AbbVie, Alliance, Argenx, Ascentage Pharma Group, AstraZeneca, Biodesix, Bio-Thera, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech-Roche, Hutchison, Immunomedics, Gilead, MT Group Merck, Nektar, Pfizer, Polynoma, Seattle Genetics, Serono-EMD, Tesaro, TG Therapeutics, Daiichi Sankyo, Exact Sciences, Boehringer Ingelheim, Laekna, Novocure, Mirati Therapeutics, Tarveda Therapeutics, Sumitomo Dainippon Pharma Oncology (formerly Boston Bio), Elpiscience Biopharma, Takeda, Vaccinex, Vincerx Pharma, Ultimovacs, Mersana. J.P. Zarate, Y. Wang, A. Chakravartty, C. Wang: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. D. Slamon: Non-Financial Interests, Personal, Member of the Board of Directors: Biomarin; Non-Financial Interests, Personal, Other, Travel expenses: Biomarin, Pfizer, Novartis; Financial Interests, Personal, Stocks/Shares: Pfizer, Amgen, Seattle Genetics; Financial Interests, Personal, Other, Research funding: Pfizer, Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Consulting: Novartis, Eli Lilly. All other authors have declared no conflicts of interest.
Presenter Of 3 Presentations
Gene-expression signature for treatment decision-making: Who to test? Which signature? (ID 426)
62P - Outcomes of high-risk breast cancer (BC) patients from El Álamo IV registry and GEICAM adjuvant clinical trials (ID 77)
- Miguel Martin Jimenez (Madrid, Spain)
- Alvaro Rodríguez-Lescure (Elche, Spain)
- Raquel Andres Conejero (Zaragoza, Spain)
- Sonia Servitja Tormo (Barcelona, Spain)
- Antonio Anton Torres (Zaragoza, Spain)
- Manuel Ruiz Borrego (Seville, Spain)
- Begona Bermejo De Las Heras (Valencia, Spain)
- Angel Guerrero (Valencia, Spain)
- Manuel Ramos Vazquez (A Coruña, Spain)
- Ana Santaballa Bertran (Valencia, Spain)
- Montserrat Munoz (Barcelona, Spain)
- J. Norberto Batista (San Cristobal de la Laguna, Spain)
- Sara Lopez-Tarruella Cobo (Madrid, Spain)
- J. Ignacio Chacon Lopez-Muniz (Toledo, Spain)
- Isabel Alvarez Lopez (San Sebastian (Donostia), Spain)
- Maria P. Martinez del Prado (Bilbao, Spain)
- Juan Jose Miralles (San Sebastian de los Reyes, Spain)
- Oscar Polonio (San Sebastian de los Reyes, Spain)
- Carlos Jara Sanchez (Alcorcon, Spain)
- Marta Mori de Santiago (Las Palmas de Gran Canaria, Spain)
Abstract
Background
Chemotherapy (CT) followed by endocrine therapy (ET) is the current standard of care for high-risk hormone receptor (HR)-positive/HER2-negative early breast cancer (EBC). The monarchE, with 27-months follow-up, showed that the addition of abemaciclib for 2 years in combination with ET improves the 3-years invasive relapse rate (IRR) and distant relapse rate (DRR) for patients (pts) with high-risk EBC. Obtaining data on the long-term risk of relapse is needed to put into context the magnitude of abemaciclib benefit.
Methods
We performed a retrospective analysis of 1742 HR-positive/HER2-negative EBC pts fulfilling the high-risk criteria of the monarchE in order to estimate their long-term outcomes. They were selected from El Álamo IV registry with pts diagnosed between 2002 and 2005 and 3 adjuvant GEICAM studies (9906, 2003-10 and 2006-10,) carried out from 1999 to 2010. Pts were divided in 2 cohorts (C), similarly to monarchE: C1) ≥ 4 positive axillary lymph nodes (PALN) or 1–3 PALN with tumor size (T) ≥ 5cm and/or histologic grade (G) 3and C2) 1–3 PALN (with T < 5cm and G < 3) and Ki-67 ≥ 20%. Pts had to have undergone surgery with curative intent and had received adjuvant CT (anthracyclines +/- taxanes) and ET.
Results
El Álamo IV registered 6374 luminal EBC pts from which 16.2% were high-risk and included in the analysis (n=1030; 981 C1, 49 C2). In addition 326 pts from 9906 (311 C1, 15 C2), 225 pts from 2003-10 (C1) and 161 pts from 2006-10 (C1) were included. With a median follow-up of 10.2 years, the IRR and DRR at 5 and 10 years were 22% and 34.8% and 19.7% and 31.0%, respectively. Per-year IRR, DRR, and death rate (DR) are described in the table. IRR and DRR increased from year 2, till year 3 followed by a second peak at years 7-8. DR increased steadily from year 1 (7.8% and 24.8% at 5 and 10 years).
Global (n=1742 pts) Times in years 1 2 3 4 5 6 7 8 9 10 IRR (%) Total 2.88 5.66 6.11 5.37 4.48 4.21 4.28 4.44 3.91 3.31 C1 2.93 5.51 6.14 5.43 4.5 4.29 4.27 4.61 3.85 3.44 C2 1.59 9.84 5.45 3.85 4 2.08 4.55 0 5.13 0 DRR (%) Total 2.70 5.23 5.44 4.57 3.83 3.65 3.83 3.22 3.64 2.64 C1 2.74 5.12 5.58 4.6 3.83 3.72 3.81 3.35 3.59 2.75 C2 1.59 8.2 1.79 3.64 3.77 1.96 4.26 0 4.76 0 DR (%) Total 0.58 1.69 2.44 3.25 3.51 3.47 4.13 4.20 4.43 4.19 C1 0.48 1.69 2.47 3.37 3.45 3.54 4.21 4.2 4.43 4.07 C2 3.13 1.61 1.64 0 5.08 1.79 1.92 4.08 4.35 6.98
Conclusions
The highest yearly risk of recurrence of high-risk EBC, defined as in monarchE, is at 3 years after diagnosis but remains high in the long-term follow-up.
Legal entity responsible for the study
GEICAM Spanish Breast Cancer Group.
Funding
LILLY.
Disclosure
M. Martin Jimenez: Financial Interests, Personal, Advisory Board: ASTRAZENECA; Financial Interests, Personal, Invited Speaker: PFIZER; Financial Interests, Personal, Invited Speaker: ASTRAZENECA; Financial Interests, Personal, Advisory Board: LILLY; Financial Interests, Personal, Invited Speaker: LILLY; Financial Interests, Personal, Invited Speaker: NOVARTIS; Financial Interests, Personal, Advisory Board: ROCHE/GENENTECH; Financial Interests, Personal, Invited Speaker: ROCHE/GENENTECH; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: NOVARTIS; Financial Interests, Institutional, Research Grant: ROCHE; Financial Interests, Institutional, Research Grant: Puma; Non-Financial Interests, Invited Speaker: TRIO; Non-Financial Interests, Leadership Role: GEICAM. B. Bermejo De Las Heras: Financial Interests, Institutional, Advisory Role: MSD, Roche, Pierre Fabre, Novartis, AstraZeneca, Seagen; Financial Interests, Institutional, Speaker’s Bureau: Pfizer, Roche, MSD, Palex, Eisai, Daiichi, AstraZeneca, Seagen. A. Guerrero: Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Advisory Board: Pfizer, Palex, Novartis, AstraZeneca, Pierre Fabre; Financial Interests, Personal, Other, Travel grant: Pfizer, Novartis; Financial Interests, Institutional, Speaker’s Bureau: Novartis, Pfizer, Lilly, AstraZeneca. A. Santaballa Bertran: Financial Interests, Institutional, Advisory Role: Pfizer. S. Lopez-Tarruella Cobo: Financial Interests, Institutional, Advisory Role: AstraZeneca, Novartis, Roche, Pfizer, Pierre Fabre, Lilly, Seagen, Daiichi Sankyo Europe GmbH, Gilead Sciences,MSD, GalaxoSmithkline, Veracyte; Financial Interests, Personal, Speaker’s Bureau: Lilly. All other authors have declared no conflicts of interest.
85P - Correlation between Prosigna® and three IHC-based surrogate intrinsic breast cancer subtype classifiers: a real world-study (ID 99)
- Miguel Martin Jimenez (Madrid, Spain)
- María Del Monte (Madrid, Spain)
- Yolanda Jerez (Madrid, Spain)
- Isabel Echavarria Diaz-Guardamino (Madrid, Spain)
- Blanca Herrero Lopez (Madrid, Spain)
- Salvador Gamez Casado (Madrid, Spain)
- Marta Roche-Molina (Madrid, Spain)
- Ivan Marquez-Rodas (Madrid, Spain)
- María Cebollero (Madrid, Spain)
- Enrique Alvarez (Madrid, Spain)
- Tatiana Massarrah (Madrid, Spain)
- Inmaculada Ocaña (Madrid, Spain)
- Ainhoa Arias (Madrid, Spain)
- Jose Angel Garcia Saenz (Madrid, Spain)
- Fernando Moreno Anton (Madrid, Spain)
- Clara Olier Garate (Alcorcon, Spain)
- Diana Moreno Muñoz (Alcorcon, Spain)
- David Marrupe Gonzalez (Mostoles, Spain)
- Tomás Merina (Madrid, Spain)
- Sara Lopez-Tarruella Cobo (Madrid, Spain)
Abstract
Background
The intrinsic subtype classification provides prognostic information on the outcome of patients with hormone receptor-positive/HER2-negative (HR+/HER2-) early breast cancer. The nCOUNTER PAM-50 test is the mRNA-based technique approved for the identification of Luminal (Lum) A and LumB tumors, to select candidates for additional adjuvant chemotherapy, mainly those with LumB tumors. Since genomic tests are expensive and not widely available, some IHC-based surrogated classifiers have been proposed based on HR, HER2 and Ki67 expression. In this real-world data analysis, we determine the ability of three different surrogate classifiers to predict the real nCOUNTER PAM-50 subtype.
Methods
Tumor samples centralized to perform the nCOUNTER PAM-50 assay in the Laboratory of Traslational Oncology at the Hospital General Universitario Gregorio Marañon between 2014 and 2020 were included in the analysis. HR and Ki67 status were determined at local laboratories. All tumors were HER2 negative by local standards. Correlation among nCOUNTER PAM-50 test and three classifiers are analysed (Cheang M et al., J Natl Cancer Inst 2009; Prat A et al., J Clin Oncol 2013; Maisonneuve P et al., Breast Cancer Res. 2014).
Results
A total of 1105 samples were analysed. 55 out of them did not have Ki67 value reported, being excluded from the analysis. From the remaining 1050 samples, 679 (64.6%) were classified as LumA and 351 (33.4%) as LumB. Concordance among these molecular subtypes by nCOUNTER PAM-50 assay and the IHC surrogated are summarized in the table. The classification based on Maisonneuve et al. 2014 showed the best correlation, although the correlation was only fair.
Prosigna kappa Lum A Lum B Cheang Lum A n=456 % 391 65 0,3397 Lum B n=573 % 287 286 Prat Lum A n=345 % 300 45 0,271 Lum B n=640 % 348 292 Maisonneuve Lum A n=607 % 490 117 0,4214 Lum B n=578 % 106 172
Conclusions
In this study, the concordance between Lum subtypes determined by 3 different IHC-based classifiers and nCOUNTER PAM-50 assay is clearly suboptimal. Between 13 - 19% of nCOUNTER PAM-50 LumB tumors were classified as LumA by IHC and could be undertreated. Conversely, between 38-54% of nCOUNTER PAM-50 LumA tumors were classified as LumB by IHC and could receive unnecessary chemotherapy.
Legal entity responsible for the study
Miguel Martín Jiménez.
Funding
Has not received any funding.
Disclosure
M. Martin Jimenez: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Astrazeneca; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Roche/Genentech; Financial Interests, Personal, Invited Speaker: Roche/Genentech; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Puma; Non-Financial Interests, Invited Speaker: Trio; Non-Financial Interests, Leadership Role: GEICAM. Y. Jerez: Financial Interests, Personal, Advisory Role: Novartis, Pfizer, Roche and AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche, Novartis and AstraZeneca; Financial Interests, Personal, Training: Roche, Novertis, Pfizer and Teva. I. Echavarria Diaz-Guardamino: Financial Interests, Personal, Invited Speaker: Eli Lilly, Pfizer, Roche, Novartis and Teva; Financial Interests, Personal, Advisory Role: Eli Lilly, Pfizer, Roche, Novartis and Teva. I. Marquez-Rodas: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Highligth Therapeutics; Financial Interests, Personal, Advisory Board: Bioline Rx; Financial Interests, Personal and Institutional, Invited Speaker, GEM1802 clinical trial: Pierre Fabre; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: Novartis; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: BMS; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: Roche; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: Pierre Fabre; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: Incyte; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: MSD; Financial Interests, Institutional, Invited Speaker, National coordinator of Spotlight 203 clinical trial: Highlight Therapeutics; Non-Financial Interests, Invited Speaker: Spanish Melanoma Group. T. Massarrah: Financial Interests, Personal, Advisory Role: AstraZeneca, Novartis, Roche; Financial Interests, Personal, Training: Novartis, AstraZeneca. J.Á. García Saenz: Financial Interests, Personal, Advisory Role: Seagen, Gilead, Sanofi; Financial Interests, Personal, Invited Speaker: Novartis, Celgene, Eli Lilly, Eisai, AstraZeneca, Daiichi Sankyo, MSD. F. Moreno Anton: Financial Interests, Personal, Invited Speaker: Novartis, Roche, Pfizer, AstraZeneca, Diachi-Sankyo, Exact Sciences, Fresenius Kabi Institution research from Pfizer; Financial Interests, Personal, Training: Novartis, Roche, Pfizer. C. Olier Garate: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer; Financial Interests, Personal, Advisory Role: Novartis, Pfizer. D. Moreno Muñoz: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer; Financial Interests, Personal, Advisory Role: Novartis, Pfizer. T. Merina: Financial Interests, Personal, Other: Oncogenomics. S. Lopez-Tarruella Cobo: Financial Interests, Personal, Advisory Role: Novartis, Pierre Fabre, Pfizer, Roche, AstraZeneca, Daiichi Sankyo, MSD, Seagen, GlaxoSmithKline, Gilead, Veracyte and Lilly; Financial Interests, Personal, Invited Speaker: Novartis, Roche, Lilly. All other authors have declared no conflicts of interest.