B. Pistilli (Villejuif, France)
Institut Gustave RoussyAuthor Of 2 Presentations
- E. Agostinetto (Brussels, Belgium)
- M. Paesmans (Brussels, Belgium)
- L. Ameye (Brussels, Belgium)
- I. Veys (Brussels, Belgium)
- L. Buisseret (Brussels, Belgium)
- P. Neven (Leuven, Belgium)
- D. Taylor (Namur, Belgium)
- C. Fontaine (Brussels, Belgium)
- F. Duhoux (Brussels, Belgium)
- J. Canon (Charleroi, Belgium)
- H. Denys (Gent, Belgium)
- F. Coussy (Paris Cedex, France)
- C. Chakiba (Bordeaux, France)
- B. Pistilli (Villejuif, France)
- M. Piccart (Brussels, Belgium)
- M. Ignatiadis (Brussels, Belgium)
- P. Aftimos (Brussels, Belgium)
72TiP - ROSALINE: a phase II, single-arm, neoadjuvant study of targeting ROS1 in combination with endocrine therapy (ET) in invAsive Lobular carcINoma of the brEast
Abstract
Background
Invasive lobular breast cancer (ILBC) is the most common histologic subtype after invasive ductal BC. It is characterized by a distinct clinical course including presentation, sites of metastatic relapse and response rates to conventional therapies. In ILBC, loss of E-cadherin (CDH1) expression is the most frequent oncogenic event (90% of cases). In vivo studies investigating synthetic lethality approaches, have shown profound antitumor effects of ROS1 inhibitors in models of E-cadherin–defective BC, providing the preclinical rationale for assessing their activity in this disease. Entrectinib is a potent small-molecule tyrosine kinase inhibitor that targets TRK, ROS1 and ALK tyrosine kinases. We aim to evaluate the combination of neoadjuvant entrectinib and ET in women with estrogen receptor positive (ER+), HER2-negative (HER2-) early ILBC.
Trial design
Single arm, multi-center, phase II trial testing entrectinib plus ET in pre/post-menopausal patients (pts) with ER+/HER2-, stage II-III (T>20mm, N0/1) ILBC. Pts will receive four 28-day cycles of letrozole (2.5 mg daily) + entrectinib (600 mg daily) +/- goserelin (3.6 mg every 28 days, only in premenopausal pts). Surgery will take place after at least 16 weeks of treatment, during weeks 17−18. Surgery and post-operative therapy will follow local practice. Primary endpoint will be residual cancer burden (RCB) 0/1 rate by local evaluation. Secondary endpoints will include pCR in breast and axilla (ypT0/Tis ypN0), tumor objective response by locally-assessed breast MRI via modified RECIST, and safety. Exploratory analyses on pre- and post-treatment tumor tissue, whole blood and plasma samples will be performed to identify differences between responders and non responders. With a two-step, optimal, Simon design with a one-sided alpha=beta=10%, we defined RCB 0/1 rate of 3% (P0) as minimal required level of activity (target RCB 0/1=15% [P1]). A futility analysis is planned on the first 17 pts. If RCB 0/1 in ≥ 1/17 pts, the study will continue until 39 evaluable subjects are enrolled. If RCB 0/1 in ≥ 3/39 pts, the combination will be considered worthy for further investigation.
Clinical trial identification
NCT04551495.
Legal entity responsible for the study
Institut Jules Bordet, Belgium.
Funding
Roche.
Disclosure
L. Buisseret: Research grant/Funding (institution): AstraZeneca; Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: iTEOS therapeutics; Speaker Bureau/Expert testimony: BMS. D. Taylor: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Lilly; Advisory/Consultancy: Daiichi Sankyo; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: AstraZeneca. F.P. Duhoux: Research grant/Funding (self), postdoctoral clinical mandate (2017-034) from a not-for-profit organisation: Foundation Against Cancer; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Teva; Speaker Bureau/Expert testimony: Mundi Pharma. H. Denys: Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Amgen; Advisory/Consultancy: Tesaro; Advisory/Consultancy: GSK; Travel/Accommodation/Expenses: PharmaMar; Travel/Accommodation/Expenses: Teva. F. Coussy: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Lilly; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis. B. Pistilli: Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Puma Biotechnology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Novartis; Advisory/Consultancy: Myriad Genetics; Advisory/Consultancy: Pierre Fabre; Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): MSD Oncology; Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): Pfizer; Research grant/Funding (self), Research grant/Funding (institution): Daiichi; Research grant/Funding (self), Research grant/Funding (institution): Merus. M. Piccart: Advisory/Consultancy, Board Member (Scientific Board): Oncolytics; Research grant/Funding (institution), Board Member (Scientific Board): Radius; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Camel-IDS; Advisory/Consultancy: Crescendo Biologics; Advisory/Consultancy: DebioPharm; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy: Huya; Advisory/Consultancy: Immunomedics; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Menarini; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Odonate; Advisory/Consultancy: Periphagen; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Seattle genetics; Research grant/Funding (institution): Servier. M. Ignatiadis: Advisory/Consultancy: Celgene; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Tesaro; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Menarini; Research grant/Funding (institution): Silicon Biosystems; Research grant/Funding (institution): Janssen Diagnostics; Travel/Accommodation/Expenses: Amgen. P.G. Aftimos: Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Macrogenics; Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Novartis; Advisory/Consultancy: Amcure; Advisory/Consultancy: Servier; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: Radius; Advisory/Consultancy: Deloitte; Honoraria (self): Synthon; Honoraria (self), Travel/Accommodation/Expenses: Amgen; Honoraria (self): Gilead; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche. All other authors have declared no conflicts of interest.
- A. Bertaut (Dijon, France)
- J. Blanc (Dijon, France)
- B. Pistilli (Villejuif, France)
- A. Dhaini Merimeche (NANCY, France)
- O. Rigal (ROUEN, France)
- C. Coutant ( Coutant ) (Dijon, France)
- M. Fournier (BORDEAUX, France)
- C. Jouannaud ( Jouannaud ) (Reims, CE, France)
- P. Soulie (ANGERS, France)
- F. Lerebours (St. Cloud, France)
- P. Cottu (Paris, CE, France)
- O. Tredan (Lyon, France)
- L. Vanlemmens (Lille, CE, France)
- C. Levy (Caen, CE, France)
- M. Mouret-Reynier (Clermont Ferrand, France)
- M. Campone (SAINT-HERBLAIN, France)
- A. Martin (Paris, France)
- A. Jacquet Jacquet (Paris, France)
- N. Briot (Dijon, France)
- I. Vaz-Luis (Villejuif, France)
151P - Impact of germline BRCA (gBRCA) mutation (m) status on clinical characteristics and patterns of care among women with early breast cancer (eBC): an analysis of the observational prospective CANTO cohort
Abstract
Background
Genetic mutations on breast cancer (BC) susceptibility genes such as BRCA 1 or 2, are well known risk factors for BC development. 5-10% of BC are associated with a gBRCAm, which can impact tumor characteristics and management of the associated BC. Using the French prospective ongoing CANTO cohort (NCT01993498) we conducted a retrospective analysis focusing on clinical characteristics and patterns of care of eBC by gBRCA status.
Methods
Data from 9368 women diagnosed with stage I to IIIa BC from 2012 to 2017 were analysed by BRCA status. Demographics, medical and family history, disease characteristics and BC treatment were examined overall and per subgroup populations.
Results
In this cohort, 169 (1.8%) patients (pts) had a gBRCAm (92 gBRCA1m and 77 gBRCA2m), 2226 (28%) were gBRCA wild type (wt) and 6573 (70.2%) gBRCA unknown (uk). Women with gBRCAm were younger than gBRCAwt or uk (mean age 43.7 years [95% CI: 42.0–45.4] versus (vs) 53.7 [53.2 - 54.1] vs 58.2 [57.9 - 58.5] respectively) at BC diagnosis. Tumours of pts with gBRCAm were characterized by higher proportion of triple negative (TN) subtype (44% [36.7-52.2] vs 13.3% [12.1 - 14.7] vs 7.9% [7.3 - 8.6]), higher stage II/IIIa (65.1% [57.4-72.2] vs 52.0% [50.0-53.9] vs 49.0% [47.8-50.2], higher histological grade 3 (67.9% [60.2-74.8] vs 32.9% [31.1-34.8] vs 25.5% [24.5-26.6]) when compared to gBRCAwt and uk pts. gBRCAm pts were more likely to undergo radical mastectomy (46.2% [35.0-50.4] vs 24.9% [23.3-26.6] vs 22.5% [21.5-23.6] ) with more axillary dissection (51.5% [43.7-59.2] vs 40.5% [38.4-42.2] vs 34.5% [33.4-35.7]) compared to gBRCAwt and uk pts. gBRCAm pts were also more likely to receive chemotherapy 92.9% [87.9-96.3] vs 56.4% [54.5-58.4] vs 49.4% [48.2-50.6] especially in the neo adjuvant setting (39.1% [31.6-46.8] vs 16.4% [15.0 -17.8] vs 11.5% [10.7-12.3]).
Conclusions
In our cohort, 30% of eBC pts had their gBRCAm status tested; of them 7.1% had gBRCAm 1 or 2. Consistent with prior research, women with gBRCAm had a substantial proportion of higher stage TN tumours and were treated with aggressive chemotherapy. Further studies on clinical outcomes of eBC pts with gBRCAm are warranted.
Clinical trial identification
NCT01993498.
Legal entity responsible for the study
UNICANCER.
Funding
This research was conducted with support from ANR (Agence Nationale de la Recherche) under the Call for Cohort Project - Investment of the Future reference ANR-10-COHO-04. The study was sponsored by AstraZeneca.
Disclosure
B. Pistilli: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Puma Biotechnology; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Myriad Genetics; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): MSD Oncology; Honoraria (self), Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Daiichi; Research grant/Funding (institution): Merus. C.C. Jouannaud: Honoraria (self): Daiichi; Honoraria (self): Sankyo; Honoraria (self), Speaker Bureau/Expert testimony: Pfizer; Travel/Accommodation/Expenses: Novartis. F. Lerebours: Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pierre Fabre; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer. M. Campone: Honoraria (self), Speaker Bureau/Expert testimony: Lilly; Honoraria (self), Speaker Bureau/Expert testimony: Accord; Honoraria (self): GT1; Honoraria (self), Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony: Servier; Speaker Bureau/Expert testimony: AbbVie; Speaker Bureau/Expert testimony: Novartis. I. Vaz-Luis: Honoraria (institution): AstraZeneca; Honoraria (institution): Amgen; Honoraria (institution): Pfizer. All other authors have declared no conflicts of interest.