Lisa A. Carey (Chapel Hill, United States of America)
Division of Medical Oncology, North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USAAuthor Of 4 Presentations
Presentation (ID 349)
25P - Research-based HER2DX in patients with early-stage HER2-positive (HER2+) breast cancer treated in the N9831 phase III clinical trial (ID 43)
- Fara Brasó-Maristany (Barcelona, Spain)
- Laia Pare Brunet (Barcelona, Spain)
- Mercedes Marín-Aguilera (Barcelona, Spain)
- Pier Franco Conte (Padova, Italy)
- Pedro Jares (Barcelona, Spain)
- Valentina Guarneri (Padova, Italy)
- Tomas Pascual (Barcelona, Spain)
- Joan A. Puig-Butille (Barcelona, Spain)
- Ana Vivancos (Barcelona, Spain)
- Joel Parker (Chapel Hill, United States of America)
- Patricia Villagrasa Gonzalez (Barcelona / Barcelona, Spain)
- Sara M. Tolaney (Boston, United States of America)
- Lisa A. Carey (Chapel Hill, United States of America)
- Charles M. Perou (Chapel Hill, United States of America)
- Aleix Prat (Barcelona, Spain)
Abstract
Background
The 27-gene HER2DX prognostic assay has been evaluated in >1300 patients (pts) with early-stage HER2+ breast cancer (BC) (EBioMedicine 2022). Here, we explored the association of the research-based HER2DX with a list of 485 genes linked to relapse-free survival (RFS) in the N9831 pivotal trial (JCO 2015).
Methods
N9831 randomized 1282 pts with early-stage HER2+ BC to adjuvant multi-agent chemotherapy (CT) (arm A), 1-year of trastuzumab starting concomitantly with CT (arm B) and 1-year of trastuzumab after CT (arm C). In JCO 2015, 485 genes were significantly (p<0.01) associated with RFS in 849 pts in arms B/C using DASL technology. Here, the primary objective was to identify available genes from the HER2DX gene list associated with RFS in arms B/C. A representation factor and the probability of finding a gene overlap were calculated. The secondary objective was to compare the expression of the N9831 485 prognostic genes in research-based HER2DX low- vs high-risk groups in 376 HER2+ BCs from METABRIC and TCGA datasets. Differentially expressed genes between both risk groups were identified (false discovery rate<5%).
Results
Five genes (CD27, CD79A, IL2RG, LAX1 and PIM2) were found in both prognostic gene lists (N9831 and HER2DX) and all belong to the HER2DX IGG signature (5 of 11 genes available; 45.5%). In N9831, the RFS hazard ratio estimate for each gene was 0.84 (CD27; p=0.002), 0.78 (CD79A; p=0.005), 0.81 (IL2RG; p=0.002), 0.85 (LAX1; p=0.008) and 0.80 (PIM2; p=0.007). The overlap between the 2 gene lists was not due to chance (enrichment factor=10.7; p<0.001). Of the genes associated with better prognosis in N9831 (n=330), 96.8% in METABRIC and 96.9% in TCGA were significantly more expressed in the research-based HER2DX low-risk group compared to the high-risk group. Of the genes associated with worse prognosis in N9831 (n=155), 66.6% in METABRIC and 35.6% in TCGA were significantly more expressed in the research-based HER2DX high-risk group compared to low-risk group.
Conclusions
The biology captured by HER2DX is significantly associated with prognostic genes found in pts treated with adjuvant trastuzumab-based CT in the N9831 trial. This result reinforces the prognostic ability of HER2DX in early-stage HER2+ BC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F. Brasó-Maristany: Financial Interests, Personal, Invited Speaker: Reveal Genomics. O. Martinez Saez: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Travel expenses: Roche. L. Pare Brunet: Financial Interests, Personal, Full or part-time Employment: Reveal Genomics. M. Marín-Aguilera: Financial Interests, Personal, Full or part-time Employment: Reveal Genomics. P.F. Conte: Financial Interests, Personal, Expert Testimony, expert testimony for drug approval with AIFA: Roche; Financial Interests, Personal, Advisory Board, advisory board for alpelisb trial: Novartis; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: Merch Kga; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Novartis. V. Guarneri: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Institutional, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Synton Biopharmaceuticals; Financial Interests, Institutional, Invited Speaker: Merck. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Lilly. A. Vivancos: Financial Interests, Personal, Other, Consultant: Sysmex; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Bristol Meyers Squibb; Financial Interests, Personal, Advisory Board: Guardant Health; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Other, Technology Transfer DX Field: Ferrer; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Bristol Meyers Squibb; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Novartis; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Debio; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: SYSMEX; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Cellestia Biotech; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Roche; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Chittern. J. Parker: Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Advisory Board: Reveal Genomics. P. Villagrasa Gonzalez: Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Officer: Reveal Genomics. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca; Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: Eli Lilly; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Novartis; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Gilead; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Genentech/Roche; Financial Interests, Personal, Other, Consultant: Nektar; Financial Interests, Personal, Other, Consultant: NanoString; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Eisai; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Sanofi; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Seagen; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Ad board participant/consultant/DSMC: Odonate; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Other, Consultant: Athenex; Financial Interests, Personal, Advisory Board, Ad board participant: OncoPep; Financial Interests, Personal, Advisory Board, Ad board participant: OncoSec; Financial Interests, Personal, Advisory Board, Ad board participant: Certara; Financial Interests, Personal, Advisory Board, Ad board participant: Mersana Therapeutics; Financial Interests, Personal, Advisory Board, Ad board participant: Ellipses Pharma; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: 4D Pharma; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Puma; Financial Interests, Personal, Invited Speaker, Invited speaker for pharma supported educational activity: Chugai Pharmaceuticals; Financial Interests, Personal, Advisory Board, Advisory board participant: G1 Therapeutics; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Personal, Advisory Board, Advisory Board participation: Zentalis; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory Board participation: OncXerna; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Eli Lilly; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Seagen; Financial Interests, Institutional, Funding: Odonate; Financial Interests, Personal and Institutional, Invited Speaker: CytomX; Financial Interests, Institutional, Funding: Cyclacel; Financial Interests, Institutional, Funding: Exelixis; Financial Interests, Institutional, Funding: Gilead; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Eisai; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Nektar; Financial Interests, Institutional, Funding: Genentech/Roche. L.A. Carey: Financial Interests, Institutional, Funding, research funding: Syndax; Financial Interests, Institutional, Funding, research funding: Immunomedics; Financial Interests, Institutional, Funding, research funding: Novartis; Financial Interests, Institutional, Funding, research funding: NanoString Technologies; Financial Interests, Institutional, Funding, research funding: AbbVie; Financial Interests, Institutional, Funding, research funding: Seattle Genetics; Financial Interests, Institutional, Funding, research funding: Veracyte; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: sanofi; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: Novartis; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: G1 Therapeutics; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: Genentech/Roche; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: GlaxoSmithKline; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: AstraZeneca/ Daiichi Sankyo; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: Apitude Health; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: Exact Sciences. C.M. Perou: Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Advisory Role: Reveal Genomics; Financial Interests, Personal, Stocks/Shares: BioClassifier LLC; Financial Interests, Personal, Advisory Role: BioClassifier LLC. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Other, Contracted research:: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Amgen; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Amgen; Financial Interests, Personal, Invited Speaker, Lecture fees: BMS; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: BMS; Financial Interests, Personal, Invited Speaker, Lecture fees: NanoString; Financial Interests, Institutional, Other, Contracted research: NanoString; Financial Interests, Institutional, Invited Speaker, Lecture fees: NanoString; Financial Interests, Institutional, Other, Contracted research: Novartis; Financial Interests, Institutional, Other, Contracted research: Roche; Financial Interests, Institutional, Other, Contracted research: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Contracted research; Financial Interests, Personal, Invited Speaker, Lecture fees: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Puma; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Oncolytics; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: MSD; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Guardan Health; Financial Interests, Personal, Expert Testimony, Advisory role/consultancy: Peptomyc; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Lilly; Financial Interests, Institutional, Other, Clinical trials: Lilly; Financial Interests, Institutional, Other, Contracted research: Boehringer; Financial Interests, Institutional, Other, Contracted research: Sysmex Europa GmbH; Financial Interests, Institutional, Other, Contracted research: Medica Scientia inno. Research; Financial Interests, Institutional, Other, Contracted research: Celgene; Financial Interests, Institutional, Other, Contracted research: Astellas; Financial Interests, Institutional, Other, Clinical trials: Roche; Financial Interests, Institutional, Other, Clinical trials: AMgen; Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.; Financial Interests, Institutional, Other, Clinical trials: Boehringer; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: Actitud Frente al Cáncer Foundation. All other authors have declared no conflicts of interest.
90TiP - Adjuvant Study of Amcenestrant (SAR439859) Versus Tamoxifen for Patients With Hormone Receptor-positive (HR+) Early Breast Cancer (EBC), Who Have Discontinued Adjuvant Aromatase Inhibitor Therapy Due to Treatment-related Toxicity (AMEERA-6) (ID 104)
- Giovanna Rossi (Brussels, Belgium)
- Etienne Brain (Saint-Claud, France)
- Amylou Dueck (Boston, United States of America)
- Heidi De Swert (Brussels, Belgium)
- Sandrine I. Marreaud (Brussels, Belgium)
- Ann Partridge (Boston, United States of America)
- Christina Herold (Brussels, Belgium)
- Hugo Vachon (Brussels, Belgium)
- Tanja Spanic (Milan, Italy)
- Amal Arahmani (Brussels, Belgium)
- Tim Verbiest (Brussels, Belgium)
- Lei Wang (Boston, United States of America)
- Theodora Goulioti (Brussels, Belgium)
- Belma Malanda (Brussels, Belgium)
- Lisa A. Carey (Chapel Hill, United States of America)
- Sandrine Anneheim (Vitry-sur-Seine, France)
- Gautier Paux (Bridgewater, United States of America)
- Coralie Poncet (Brussels, Belgium)
- Otto Metzger (Boston, United States of America)
- David Cameron (Edinburgh, United Kingdom)
Abstract
Background
About 30% of patients (pts) with HR+ EBC on treatment with aromatase inhibitors (AIs), discontinue AIs due to toxicity (Henry et al. JCO 2012). For this population, there are currently limited therapy options, including switch to another AI or tamoxifen. Amcenestrant is an optimized oral selective estrogen receptor degrader (SERD) with potent dual activity which antagonizes and degrades the estrogen receptor (ER), resulting in inhibition of the ER signaling pathway. In the phase 1/2 AMEERA-1 trial (SABCS 2020 PD8-08), amcenestrant showed strong antitumor activity and favorable safety profile in the treatment of HR+ metastatic breast cancer.
Trial design
This is a prospective, randomized, international, double-blind, double-dummy, phase 3 superiority study. Eligible pts are men and pre/peri/post-menopausal women with HR+ stage IIB/III breast adenocarcinoma, irrespective of human epidermal growth factor receptor 2 (HER2) status. Pts will be centrally assessed to have ER+ and/or progesterone receptor (PgR)+ (≥10% positive stained cells) status by immunohistochemistry assay. Pts must have received at least 6 months of adjuvant AIs (≥3 months in the adjuvant setting if they have received prior neoadjuvant AIs) and discontinued them within 30 months of initiation due to treatment-related toxicity. Any anti-HER2 treatment, chemotherapy or cyclin-dependent kinase (CDK) 4/6 inhibitor are allowed if completed or stopped prior to randomization. 3738 pts will be randomized 1:1 to receive either amcenestrant 200 mg daily or tamoxifen 20 mg daily for 5 years and will be followed up for 10 years from randomization. Stratification factors include AIs duration, HER2 status, prior chemotherapy, prior CDK4/6 inhibitors, geographic region, menopausal status. The primary endpoint is invasive breast cancer-free survival (IBCFS) (STEEP v 2.0); key secondary endpoint is invasive disease-free survival and other secondary endpoints are overall survival, safety, patient reported outcomes. Adherence to treatment is an exploratory endpoint. AMEERA-6 opened for recruitment in January 2022.
Clinical trial identification
NCT05128773.
Legal entity responsible for the study
Sanofi.
Funding
Sanofi.
Disclosure
G. Rossi: Financial Interests, Institutional, Royalties: Agendia; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: SERVIER; Financial Interests, Institutional, Research Grant: Biovica; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Sanofi/Aventis. E. Brain: Financial Interests, Personal, Other, Honoraria: Eli Lilly; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Sandoz; Financial Interests, Personal, Other, Honoraria: Seagen; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Other, Travel, accommodations, expenses: Pfizer; Financial Interests, Personal, Other, Travel, accommodations, expenses: Sandoz. H. De Swert: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Servier; Financial Interests, Institutional, Research Grant: BIOVICA; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Sanofi/Aventis; Financial Interests, Institutional, Royalties: Agendia. C. Herold: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi; Financial Interests, Personal, Other, Travel, accommodations, expenses: Sanofi. T. Spanic: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Gilead. A. Arahmani: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: BIOVICA; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: TESARO; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: SERVIER; Financial Interests, Institutional, Royalties: Agendia. L. Wang: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Syndax Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Ikena Oncology. T. Goulioti: Financial Interests, Personal, Full or part-time Employment, An Immediate Family Member: UCB; Financial Interests, Personal, Stocks/Shares, An Immediate Family Member: GlaxoSmithKline; Financial Interests, Personal, Ownership Interest, An Immediate Family Member: UCB; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Research Grant: SERVIER; Financial Interests, Institutional, Research Grant: Biovica; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Sanofi/Aventis; Financial Interests, Institutional, Royalties: Agendia. S. Anneheim: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. G. Paux: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi; Financial Interests, Personal, Royalties: Sanofi. O. Metzger: Financial Interests, Personal, Stocks/Shares: Invitae; Financial Interests, Personal, Other, Honoraria: Grupo Oncoclinicas; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Advisory Board: Grupo Oncoclinicas; Financial Interests, Personal, Advisory Board: Resilience Care; Financial Interests, Personal, Advisory Board: Alliance for Clinical Trials in Oncology; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Susan G. Komen for the Cure; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Cascadian Therapeutics; Financial Interests, Institutional, Royalties: Sanofi; Financial Interests, Personal, Other, Travel, accommodations, expenses: Grupo Oncoclinicas. D. Cameron: Financial Interests, Personal, Advisory Board: Aptitude Health; Financial Interests, Personal, Advisory Board: Roche Sweden; Financial Interests, Personal, Advisory Board: Pfizer Limited; Financial Interests, Personal, Advisory Board: Celldex Therapeutics Inc.; Financial Interests, Personal, Advisory Board: Carnall Farrar; Financial Interests, Personal, Advisory Board: San Antonio Breast Cancer Consortium; Financial Interests, Personal, Advisory Board: Highfield Communication; Financial Interests, Personal, Advisory Board: AstraZeneca Global Commercial Organisation - Egypt; Financial Interests, Personal, Advisory Board: Celgene Corporation; Financial Interests, Personal, Advisory Board: Chief Scientists Office; Financial Interests, Personal, Advisory Board: Cancer Research UK; Financial Interests, Personal, Advisory Board: HTA; Financial Interests, Personal, Advisory Board: Samsung Bioepis Co Ltd. (Korea); Financial Interests, Personal, Advisory Board: Eli Lilly & Company; Financial Interests, Personal, Advisory Board: Costello Medical Consulting Ltd.; Financial Interests, Personal, Advisory Board: prIME Oncology; Financial Interests, Personal, Advisory Board: AstraZeneca UK Limited; Financial Interests, Personal, Advisory Board: Roche Products Ltd.; Financial Interests, Personal, Advisory Board: Novartis Pharma AG; Financial Interests, Personal, Advisory Board: Novartis Pharmaceuticals Corporation; Financial Interests, Personal, Advisory Board: Pfizer Limited; Financial Interests, Personal, Advisory Board: PFS Ltd.; Financial Interests, Personal, Advisory Board: Novartis Pharmaceuticals UK Limited; Financial Interests, Personal, Advisory Board: Merck Sharp Dohme Limited; Financial Interests, Personal, Advisory Board: Puma Biotechnology, Inc.; Financial Interests, Personal, Advisory Board: Pfizer Limited; Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche AG; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Advisory Board: Breast International Group (BIG); Financial Interests, Personal, Advisory Board: Breast Cancer Institute; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, USA; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Elsevier Ltd.; Financial Interests, Personal, Advisory Board: European Cancer Organisation; Financial Interests, Personal, Advisory Board: Exact Therapeutics; Financial Interests, Personal, Advisory Board: G1 Therapeutics; Financial Interests, Personal, Advisory Board: Galapagos NV; Financial Interests, Personal, Advisory Board: Genentech Inc.; Financial Interests, Personal, Advisory Board: GSK (Glaxo SmithKline); Financial Interests, Personal, Advisory Board: ICON Clinical Research; Financial Interests, Personal, Advisory Board: Prima BioMED; Financial Interests, Personal, Advisory Board: RTI Health Solutions; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Synthon Biopharmaceuticals BV: Note name change to Byondis April 2020; Financial Interests, Personal, Advisory Board: Succinct Medical Communications; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: SANOFI; Financial Interests, Personal, Advisory Board: Sapience Therapeutics Ltd.; Financial Interests, Personal, Advisory Board: Bexon/Zymeworks Biopharmaceuticals Inc.; Financial Interests, Personal, Advisory Board: Make Seconds Count. All other authors have declared no conflicts of interest.
168P - Sacituzumab govitecan (SG) efficacy in patients with metastatic triple-negative breast cancer (mTNBC) by HER2 immunohistochemistry (IHC) status: Findings from the Phase 3 ASCENT study (ID 176)
- Sara A. Hurvitz (Los Angeles, United States of America)
- Aditya Bardia (Boston, United States of America)
- Kevin Punie (Leuven, Belgium)
- Kevin Kalinsky (Atlanta, United States of America)
- Javier Cortes (Madrid and Barcelona, Spain)
- Joyce O'Shaughnessy (Dallas, United States of America)
- Lisa A. Carey (Chapel Hill, United States of America)
- Hope S. Rugo (San Francisco, United States of America)
- Oh Kyu Yoon (Foster City, United States of America)
- Yang Pan (Foster City, United States of America)
- Rosemary J. Delaney (Foster City, United States of America)
- Scott Hofsess (Foster City, United States of America)
- Paul Hodgkins (Foster City, United States of America)
- See-Chun Phan (Foster City, United States of America)
- Veronique Dieras (Rennes, France)
Abstract
Background
HER2 IHC1+ or IHC2+ and in situ hybridization (ISH)-negative results are sometimes referred to as HER2-Low. SG is a novel antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to SN-38 via a proprietary, hydrolyzable linker. SG is approved in mTNBC for the second line (2L) onwards. In the ASCENT study, SG had significant progression-free survival (PFS) and overall survival (OS) benefit vs chemotherapy of physician’s choice (TPC). This ASCENT post hoc subgroup analysis evaluates SG efficacy in HER2 IHC0 and HER2-Low mTNBC.
Methods
Patients (pts) with mTNBC refractory/relapsing after ≥2 prior chemotherapies (≥1 in the metastatic setting) were randomized 1:1 to receive SG (10 mg/kg IV on d 1 and 8, every 21 d) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until unacceptable toxicity/progression. Primary endpoint was PFS per RECIST 1.1 by central review. Pts with known HER2-positive disease were ineligible, but HER2 status was not assessed centrally in ASCENT. Local HER2 IHC results were analyzed retrospectively.
Results
In the intent-to-treat (ITT) population (SG vs TPC), 149 vs 144, 63 vs 60, and 55 vs 58 pts had HER2 IHC0, HER2-Low, and missing HER2 IHC results, respectively; 79% of the ITT population was HER2-evaluable. Baseline characteristics between HER2 IHC0 vs HER2-Low were comparable and similar to the ITT population. Median PFS and OS were significantly improved, and objective response rate was numerically higher with SG vs TPC in the HER2 IHC0 and HER2-Low groups (Table). HER2-Low had numerically better outcomes vs HER2 ICH0 in both the SG and TPC arms.
Conclusions
Clinical benefit with SG in HER2 IHC0 and HER2-Low mTNBC was consistent with that of the ASCENT ITT population, regardless of HER2 status. SG should be considered an effective treatment option for pts with mTNBC eligible for 2L or later therapy. ISH, in situ hybridization; HR, hazard ratio; IHC, immunohistochemistry; mPFS, median progression-free survival; mOS, median overall survival, ORR, objective response rate; SG, sacituzumab govitecan; TPC, treatment of physician’s choice ∗HER2-Low defined as IHC1+ or ICH2+ and ISH-neg
HER2 IHC0 HER2-Low∗ SG (n=149) TPC (n=144) SG (n=63) TPC (n=60) mPFS, mo 4.3 1.6 6.2 2.9 HR (95% CI) 0.38 (0.28-0.50) 0.44 (0.27-0.72) mOS, mo 11.3 5.9 14.0 8.7 HR (95% CI) 0.51 (0.39-0.66) 0.43 (0.28-0.67) ORR, n (%) 46 (31) 5 (3) 20 (32) 5 (8)
Clinical trial identification
NCT02574455.
Editorial acknowledgement
Editorial support was provided by Yao Bian, PhD, of Team 9 Science and funded by Gilead Sciences, Inc.
Legal entity responsible for the study
Gilead Sciences, Inc.
Funding
Gilead Sciences, Inc.
Disclosure
S.A. Hurvitz: Financial Interests, Personal, Invited Speaker: Clinical Care Options; Financial Interests, Personal, Invited Speaker: aptitude health; Financial Interests, Personal, Invited Speaker: axis medical; Financial Interests, Personal, Invited Speaker: cancer expert now; Financial Interests, Personal, Invited Speaker: ICHE; Financial Interests, Personal, Invited Speaker: MJH Associates; Financial Interests, Personal, Invited Speaker: PER; Financial Interests, Personal, Invited Speaker: Primo; Financial Interests, Personal, Invited Speaker: Projects in Knowledge; Financial Interests, Personal, Invited Speaker: Prova Education; Financial Interests, Personal, Invited Speaker: Research to Practice; Financial Interests, Personal, Invited Speaker: Ultimate Medical Academy; Financial Interests, Personal, Invited Speaker: Vaniam; Financial Interests, Personal, Invited Speaker: WebMD; Financial Interests, Personal, Invited Speaker: Rockpointe; Financial Interests, Personal, Invited Speaker: OBR; Financial Interests, Personal, Invited Speaker: Peer Education; Financial Interests, Personal, Invited Speaker: Spire Learning; Financial Interests, Personal, Invited Speaker: PrecisCA; Financial Interests, Personal, Stocks/Shares, stock options: NK Max; Financial Interests, Personal, Stocks/Shares, spouse owns: ROM Tech; Financial Interests, Personal, Ownership Interest, spouse: Ideal Implant; Financial Interests, Personal, Royalties, author medical book: McGraw; Financial Interests, Personal, Royalties: Elsevier; Financial Interests, Personal, Royalties: Springer; Financial Interests, Personal, Royalties: Sage; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Royalties: Wiley; Financial Interests, Institutional, Invited Speaker: Ambrx; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Arvinas; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Genentech/Roche; Financial Interests, Institutional, Invited Speaker: Gilead; Financial Interests, Institutional, Invited Speaker: GSK; Financial Interests, Institutional, Invited Speaker: Immunomedics; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: OBI Pharma; Financial Interests, Institutional, Invited Speaker: Pieris; Financial Interests, Institutional, Invited Speaker: Puma; Financial Interests, Institutional, Invited Speaker: Radius; Financial Interests, Institutional, Invited Speaker: sanofi; Financial Interests, Institutional, Invited Speaker: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Dignitana; Financial Interests, Institutional, Invited Speaker: Zymeworks; Financial Interests, Institutional, Invited Speaker: Phoenix Molecular Designs, Ltd.; Financial Interests, Institutional, Research Grant: Samumed; Financial Interests, Institutional, Research Grant: Ambrx; Non-Financial Interests, Advisory Role: Daiichi Sankyo; Non-Financial Interests, Principal Investigator: Daiichi Sankyo; Non-Financial Interests, Advisory Role: Novartis; Non-Financial Interests, Principal Investigator: Genentech; Non-Financial Interests, Principal Investigator: Seattle Genetics; Non-Financial Interests, Advisory Role: Ambrx; Non-Financial Interests, Advisory Role: 4DPharma; Non-Financial Interests, Advisory Role: Dantari; Non-Financial Interests, Advisory Role: Macrogenics; Non-Financial Interests, Advisory Role: Lilly; Non-Financial Interests, Advisory Role: Artios; Non-Financial Interests, Advisory Role: Roche; Non-Financial Interests, Advisory Role: Pyxis; Non-Financial Interests, Advisory Role: Amgen; Non-Financial Interests, Advisory Role: Pieris; Non-Financial Interests, Advisory Role: Arvinas; Non-Financial Interests, Advisory Role: Immunomedics/Gilead; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member: AACR; Non-Financial Interests, Other, speaker: National Breast Cancer Coalition; Non-Financial Interests, Member, site representative for breast cancer guidelines: National Comprehensive Cancer Network. A. Bardia: Financial Interests, Institutional, Financial Interests, grants: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health/Menarini, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly; Financial Interests, Personal, Financial Interests, consulting fees: Pfizer, Novartis, Genentech, Merck, Radius Health/Menarini, Immunomedics/Gilead, Sanofi, Daiichi Pharma/AstraZeneca, Phillips, Eli Lilly, Foundation Medicine. K. Punie: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Advisory Board: Vifor Pharma; Financial Interests, Institutional, Advisory Board: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Mundi Pharma; Financial Interests, Institutional, Advisory Board: Pierre Fabre; Financial Interests, Institutional, Advisory Board: McCann Health; Financial Interests, Institutional, Advisory Board: Roularta; Financial Interests, Institutional, Advisory Board: Teva; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board: Gilead Sciences; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Other, Consultancy: Roche; Financial Interests, Institutional, Funding: Sanofi; Non-Financial Interests, Principal Investigator: EORTC 1745-ETF-BCG trial; Non-Financial Interests, Other, Committee member: ESMO Young Oncologists Committee; Non-Financial Interests, Invited Speaker: BSMO; Non-Financial Interests, Other, Committee Member: ESMO Resilience Task Force; Non-Financial Interests, Advisory Role: Commission personalized medecine Federal Government Belgium. K. Kalinsky: Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Immunomedics; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Cyclacel; Financial Interests, Personal, Advisory Board: Oncosec; Financial Interests, Personal, Advisory Board: 4D Pharma; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Stocks/Shares, Employment + Stock = spouse: Grail; Financial Interests, Institutional, Invited Speaker: Incyte; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Genentech; Financial Interests, Institutional, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Calithera; Financial Interests, Institutional, Invited Speaker: Immunomedics; Financial Interests, Institutional, Invited Speaker: Acetylon; Financial Interests, Institutional, Invited Speaker: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: Zentalis; Financial Interests, Institutional, Invited Speaker: CytomX Therapeutics; Other, Support for attending meetings and/or travel: Eli Lilly; Other, Support for attending meetings and/or travel: AstraZeneca; Other, Support for attending meetings and/or travel: Pfizer; Other, Steering Committee: Immunomedics; Other, Steering Committee: AstraZeneca; Other, Steering Committee: Ambryx; Other, Steering Committee: Genentech. J. Cortés: Financial Interests, Personal, Financial Interests, stock: Leuko, MedSIR, Nektar; Financial Interests, Personal, Financial Interests, honoraria: Novartis, Eisai, Celgene, Pfizer, Roche, Samsung, Lilly, Merck Sharp & Dohme, Daachi Sankyo; Financial Interests, Personal, Financial Interests, consulting or advisory role: Celgene, Cellestia Biotech, AstraZeneca, Roche, Seattle Genetics, Daachi Sankyo, ERYTECH Pharma, Polyphor, Athenex, Lilly, Servier, Merck Sharp & Dohme, GlaxoSmithKline, Leuko, Clovis Oncology, Bioasis, Boehringer, Ingelheim, Ellipses Pharma, HiberCell; Financial Interests, Institutional, Financial Interests, research funding: Ariad, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer, Eisai Farmaceutica, Guardaanth Health, Merck Sharp & Dohme, Pfizer, Puma Co, Queen Mary University of London, Roche, Piqur; Financial Interests, Personal, Financial Interests, travel, accomodations, expenses: Roche, Pfizer, Eisai, Novartis, Daiichi Sankyo. J. O'Shaughnessy: Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Agendia; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Aptitude Health; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: G1 Therapeutics; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Immunomedics; Financial Interests, Personal, Advisory Board: Ipsen Biopharmaceuticals; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Myriad; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Ondonate; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: prIME Oncology; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Syndax. H.S. Rugo: Financial Interests, Personal, Invited Speaker: Puma; Financial Interests, Personal, Advisory Board: samsung; Financial Interests, Personal, Invited Speaker: mylan; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: OBI Pharma; Financial Interests, Institutional, Invited Speaker: Immunomedics; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker: Daiichi; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Odonate; Financial Interests, Institutional, Invited Speaker: sermonix; Financial Interests, Institutional, Invited Speaker: seattle genetics; Financial Interests, Institutional, Invited Speaker: polyphor; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. O.K. Yoon: Financial Interests, Personal, Financial Interests, employee, stock options: Gilead. Y. Pan: Financial Interests, Personal, Financial Interests, employee: Gilead. R.J. Delaney: Financial Interests, Personal, Financial Interests, employee, stock or stock options: Gilead. S. Hofsess: Financial Interests, Personal, Financial Interests, employee, meeting attendance, stock options: Gilead; Non-Financial Interests, Personal, Non-Financial Interests, unpaid: Chair of the William Paterson University Professional Science Master’s External Advisory Board. P. Hodgkins: Financial Interests, Personal, Financial Interests, employee, stock options: Gilead Sciences. S. Phan: Financial Interests, Personal, Financial Interests, employee, grants or contracts, meeting attendance, stock or stock options, receipt of materials: Gilead. V. Dieras: Financial Interests, Personal, Financial Interests, consulting fees: Roche Genentech, Novartis, Pfizer, Lilly, AbbVie, Eisai, AstraZeneca, Daiichi Sankyo, Seagen, Gilead, MSD, Pierre Fabre Oncologie; Financial Interests, Personal, Financial Interests, honoraria: Novartis, Pfizer, Lilly, AstraZeneca, Seagen, Daiichi Sankyo, Gilead, MSD; Financial Interests, Personal, Financial Interests, meeting attendance and/or travel: Roche, Novartis, Pfizer, Seagen, Lilly, AstraZeneca, Daiichi Sankyo, Gilead; Financial Interests, Personal, Financial Interests, data safety monitoring board or advisory board: Roche Genentech, Novartis, Pfizer, Lilly, AbbVie, Eisai, AstraZeneca, Daiichi Sankyo, Seagen, Gilead, MSD, Pierre Fabre Oncologie. All other authors have declared no conflicts of interest.