P. Cottu (Paris, CE, France)
Institut CurieAuthor Of 1 Presentation
63O - Letrozole and palbociclib versus 3rd generation chemotherapy as neoadjuvant treatment in luminal breast cancer: survival results of the UNICANCER-NeoPAL study (ID 239)
Abstract
Background
The NeoPAL trial compared letrozole-palbociclib (LETPAL) combination to standard chemotherapy (CT) as neoadjuvant treatment in patients with high-risk LBC. Both LETPAL and CT were associated with poor pathological response, and equivalent clinical responses, while LETPAL let to encouraging biomarker responses in Prosigna®-defined high-risk LBC. We now evaluate the survival outcomes of both groups.
Methods
NeoPAL (UCBG104, NCT02400567) is a randomized, parallel, non-comparative phase II study. Postmenopausal women with ER-positive, HER2-negative, Prosigna®-defined luminal B, or luminal A and node-positive, stage II-III BC, were randomly assigned to either letrozole (2.5 mg daily) and palbociclib (125 mg daily, 3 weeks/4) during 19 weeks (LETPAL), or to FEC100 (5FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) x3 21-day courses followed by docetaxel 100 mg/m2 x3 21-day courses (CT). Secondary endpoints included progression-free survival (PFS) and invasive-disease free survival (iDFS), all measured from the date of randomization. Exploratory objectives aimed at evaluating the impact of PEPI score and residual cancer burden (RCB) on survival outcomes in both arms.
Results
53 pts were randomized in each arm. 23 of the 53 pts in the LETPAL arm received postoperative adjuvant chemotherapy. Median follow-up is 40.4 months [0-56.6]. 11 progressions have been observed, of which 3 were in the LETPAL and 8 in the control arm. Two additional iDFS events were observed in the LETPAL arm (secondary malignancies). PFS (HR = 1.01; 95%CI [0.36; 2.90], p=0.98) and iDFS (HR= 0.83; 95%CI [0.31; 2.23], p=0.71) did not differ between both arms. 40 months PFS rate is 86.7% (78.0-96.4) and 87.2% (78.1-97.4) in LETPAL and CT arms respectively. PEPI (PEPI II/II vs I: HR 0.80, 95%CI 0.18-3.67) and RCB scores (RCB II/III vs 0/I: HR 1.36; 95%CI 0.17-10.6) did not appear as independent predictors of PFS or iDFS.
Conclusions
Despite its small size, NeoPAL suggests that a neoadjuvant LETPAL strategy, together with selected postoperative administration of chemotherapy, may spare chemotherapy in some pts with LBC while allowing good long-term outcomes.
Clinical trial identification
NCT02400567.
Legal entity responsible for the study
UNICANCER.
Funding
Pfizer, NanoString Technologies.
Disclosure
S. Delaloge: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Orion; Research grant/Funding (institution): Daiichi; Research grant/Funding (institution): Puma; Research grant/Funding (institution): Pierre Fabre. H. Manduzio, J. Lemonnier, P.H. Cottu: Research grant/Funding (institution): Pfizer. All other authors have declared no conflicts of interest.
Author Of 1 Presentation
- 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.