S. Delaloge (Paris, France)
Institut Gustave RoussyAuthor Of 3 Presentations
Adjuvant chemotherapy in hormone-receptor positive tumours: Who to treat and which regimen? (ID 4)
43O - Pertuzumab/Trastuzumab in Early Stage HER2-positive Breast Cancer: 5-year and Final Analysis of the BERENICE Trial (ID 235)
Abstract
Background
BERENICE was designed to establish the cardiac safety of neoadjuvant pertuzumab/trastuzumab (PH) with anthracycline-containing chemotherapies (primary objective). Here we report the 5-year outcomes at end-of-study (clinical cut-off date: 25/08/2020), including additional safety and efficacy data (secondary objectives).
Methods
BERENICE was a multicenter, open-label, non-comparative phase II trial. Patients with stage IIA to III HER2-positive breast cancer and a left ventricular ejection fraction (LVEF) ≥55% were allocated per physician's choice to cohort A (dose-dense doxorubicin/cyclophosphamide every 2 weeks [q2w] x 4 → paclitaxel q1w x 12) or cohort B (5-fluorouracil, epirubicin, cyclophosphamide q3w x 4 → docetaxel q3w x 4). PH q3w was initiated from the start of taxanes and continued after surgery for a total of 17 cycles.
Results
Intention-to-treat population comprised 199 patients in cohort A and 201 in cohort B, with a median follow-up of 64.5 months. No new cardiac safety issues were seen, with few events occurring in the treatment-free period and a low incidence of class III/IV congestive heart failure (Table). Event-free survival (EFS) rates at 5 years were 90.8% (95% CI, 86.5-95.2) and 89.2% (84.8-93.6) in cohorts A and B, respectively. Overall survival rates at 5 years were 96.1% (93.3-98.9) and 93.8% (90.3-97.2) in cohorts A and B, respectively. According to PAM50 classification, available for 339 patients, most patients had HER2-enriched tumors (51.6%), with 5-year EFS rates of 93.1% (87.2-98.9) in cohort A and 88.3% (81.8-94.8) in cohort B *3 patients without safety data available
Safety population Cohort A (N=199) Cohort B (N=198)* No. of patients with at least one LVEF decrease to ≥10% points from baseline to an LVEF <50% (whole study) No. during the treatment-free follow-up period 27 (13.6%) 12 (6.0%) 24 (12.1%) No. of patients with New York Heart Association class III/IV congestive heart failure (whole study) 3 (1.5%) 2 (1.0%)
Conclusions
The final analysis of BERENICE showed sustained cardiac safety and favorable long-term efficacy outcomes, further supporting neoadjuvant/adjuvant PH with standard anthracycline-containing therapies in patients with early stage HER2-positive breast cancer.
Clinical trial identification
NCT02132949 (WO29217), 25 January 2014.
Editorial acknowledgement
Support for third-party writing assistance for this abstract, furnished by Alison McGonagle, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
C. Dang: Honoraria (self): F. Hoffmann-La Roche Ltd., Genentech Inc., Daiichi Sankyo, Lilly, Puma Biotechnology; Advisory/Consultancy: F. Hoffmann-La Roche Ltd., Genentech Inc., Daiichi Sankyo, Lilly, Puma Biotechnology; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. M.S. Ewer: Advisory/Consultancy: AstraZeneca, Bayer, Boehringer Ingelheim; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions.: Roche. S. Delaloge: Advisory/Consultancy: AstraZeneca, Pierre Fabre, BMS, Roche, Lilly, Novartis, Pfizer, Servier, Orion, Puma, Sanofi, Cellectis; Research grant/Funding (institution): AstraZeneca, Roche, GE, Pfizer, Puma, Sanofi, BMS, MSD; Travel/Accommodation/Expenses: Pfizer, Roche, AstraZeneca; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. J-M. Ferrero: Honoraria (self): Pfizer, Lilly, Novartis; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. R. Colomer: Advisory/Consultancy: Roche, Lilly, MSD, AstraZeneca; Research grant/Funding (self): Roche, Lilly, MSD, BMS; Travel/Accommodation/Expenses: Roche, MSD; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. L. de la Cruz Merino: Advisory/Consultancy: MSD, Roche, Celgene; Speaker Bureau/Expert testimony: MSD, Roche, BMS, Amgen; Research grant/Funding (institution): BMS, Roche; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. K. Dadswell: Shareholder/Stockholder/Stock options: Roche; Full/Part-time employment: Roche; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. M. Verrill: Honoraria (self): Roche, Lilly, Pfizer, Novartis, Exact Sciences; Research grant/Funding (institution): Roche, Pfizer, Amgen, Novartis; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. D. Eiger: Research grant/Funding (self): Novartis; Shareholder/Stockholder/Stock options: Roche; Full/Part-time employment: Roche; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. S. Sarkar: Full/Part-time employment, Roche external business partner: PAREXEL; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. S. de Haas: Full/Part-time employment: Roche; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. E. Restuccia: Shareholder/Stockholder/Stock options: Roche; Full/Part-time employment: Roche; Non-remunerated activity/ies, Third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche. S.M. Swain: Honoraria (self): AstraZeneca, Daiichi Sankyo, Roche/Genentech, Exact Sciences (Genomic Health), Molecular Templates, Silverback Therapeutics, Tocagen, Lilly, Natera, Athenex, Bejing Medical Foundation; Advisory/Consultancy: AstraZeneca, Daiichi Sankyo, Roche/Genentech, Exact Sciences (Genomic Health), Molecular Templates, Silverback Therapeutics, Tocagen, Lilly, Natera, Athenex, Bejing Medical Foundation; Advisory/Consultancy, Scientific advisory board: Inivata; Research grant/Funding (institution): Roche/Genentech, Kailos Genetics; Travel/Accommodation/Expenses: BMS, Lilly, Roche/Genentech, Daiichi Sankyo, Caris Life Sciences; Non-remunerated activity/ies, Support for third-party editorial assistance, furnished by Alison McGonagle, PhD, of Health Interactions: Roche.
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.
Presenter Of 2 Presentations
Adjuvant chemotherapy in hormone-receptor positive tumours: Who to treat and which regimen? (ID 4)
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.