All times are listed in CEST (Central European Summer Time)
- Javier Cortés (Barcelona, Spain)
- Sherko Kümmel (Essen, Germany)
LBA11 - IMpassion031: Results from a phase III study of neoadjuvant (neoadj) atezolizumab + chemotherapy in early triple-negative breast cancer (TNBC)
- Nadia Harbeck (Munich, Germany)
Abstract
Background
Preferred neoadj regimens for patients (pts) with early-stage (e)TNBC include taxane + anthracycline–based therapy. IMpassion031 is a global, phase III, multicentre, double-blind, randomised, placebo-controlled study in pts with high-risk primary invasive eTNBC evaluating the efficacy and safety of neoadj atezolizumab (A) or placebo (P) with
Methods
Eligible pts were ≥ 18 years old with previously untreated, centrally confirmed, invasive stage II-III eTNBC and tumour size > 2 cm. Pts (n = 333) were randomized 1:1 to receive A 840 mg or P q2w + nP 125 mg/m2 qw for 6 doses of A followed by A 840 mg or P q2w + doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 q2w for 4 doses of A followed by surgery. After surgery, pathologic complete response (pCR; ypT0/isN0) was assessed in all pts and investigators were unblinded to study treatment. Stratification was by diagnosis stage (II vs III) and PD-L1 expression on tumour-infiltrating immune cells (IC; ≥ 1% vs < 1%). Co-primary endpoints were locally assessed pCR in ITT or PD-L1+ (PD-L1 IC ≥ 1%) pts. Event-free survival (EFS) was a secondary endpoint. Safety was assessed.
Results
333 pts were assigned to A-chemo (n = 165) or P-chemo (n = 168). Median follow-up was 20.6 mos in the A-chemo arm and 19.8 mos in the P-chemo arm (data cutoff 3 Apr 2020). pCR was seen in 57.6% (95% CI: 49.7, 65.2) of pts in the A-chemo arm and 41.1% (33.6, 48.9) in the P-chemo arm (Δ16.5%; 5.9, 27.1; 1-sided
Conclusions
In pts with eTNBC, A + neoadj chemo significantly improved pCR rates regardless of PD-L1 status with an acceptable safety profile.
Clinical trial identification
NCT03197935.
Editorial acknowledgement
Medical writing assistance for this abstract was provided by Christopher Lum, PhD of Health Interactions, Inc.
Legal entity responsible for the study
F. Hoffmann-La Roche, Ltd.
Funding
F. Hoffmann-La Roche, Ltd.
Disclosure
N. Harbeck: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche. H. Zhang: Research grant/Funding (institution), Non-financial support: F. Hoffmann-La Roche. C.H. Barrios: Advisory/Consultancy: Boehringer-Ingelheim; Advisory/Consultancy: Glaxo-Smith-Kline; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp Dohme; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Bayer; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Covance; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): CPO; Research grant/Funding (institution): PUCRS; Research grant/Funding (institution): LACOG; Research grant/Funding (institution): GBECAM; Research grant/Funding (institution): INCA-Brazil. S. Saji: Research grant/Funding (institution), Non-financial support: F. Hoffmann-La Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Lecture, Consultation: Chugai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Lecture, Consultation: Kyowa Kirin; Honoraria (self), Research grant/Funding (institution), Lecture: Eli Lilly; Honoraria (self), Research grant/Funding (institution), Lecture: AstraZeneca; Honoraria (self), Lecture: Pfizer; Honoraria (self), Lecture: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Lecture, Consultation: Novartis; Honoraria (self), Research grant/Funding (institution), Lecture: Eisai; Honoraria (self), Research grant/Funding (institution), Lecture: Takeda; Research grant/Funding (institution): Taiho. K.H. Jung: Honoraria (self), Research grant/Funding (institution), Personal fees, Non-financial support: F. Hoffmann-La Roche; Honoraria (self), Personal fees: Novartis; Honoraria (self), Personal fees: AstraZeneca; Honoraria (self), Personal fees: Takeda; Honoraria (self), Personal fees: Celgene. R. Hegg: Research grant/Funding (institution), Non-financial support: F. Hoffmann-La Roche. A. Koehler: Research grant/Funding (institution), Travel/Accommodation/Expenses, Non-financial support: F. Hoffmann-La Roche; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Celgene; Travel/Accommodation/Expenses: Amgen. J. Sohn: Research grant/Funding (institution), Non-financial support: F. Hoffmann-La Roche; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Contessa; Research grant/Funding (institution): Daiichi Sankyo. H. Iwata: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Daiichi-Sankyo; Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Kyowa Hakko Kirin; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Boehringer-Ingelheim; Research grant/Funding (institution): Nihon Kayaku; Research grant/Funding (institution): Sanofi. M.L. Telli: Research grant/Funding (institution), Non-financial support: F. Hoffmann-La Roche; Honoraria (self), Research grant/Funding (institution), Personal fees, Non-financial support: AbbVie; Honoraria (self), Research grant/Funding (institution), Personal fees, Non-financial support: Pfizer; Honoraria (self), Research grant/Funding (institution), Personal fees, Non-financial support: Merck; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Vertex; Honoraria (self), Personal fees: Lilly; Honoraria (self), Personal fees: Immunomedics; Honoraria (self), Personal fees, Non-financial support: Celgene; Honoraria (self), Personal fees: G1 Therapeutics; Honoraria (self), Personal fees: Daiichi Sankyo; Honoraria (self), Personal fees: Aduro; Honoraria (self), Personal fees: Celldex; Honoraria (self), Research grant/Funding (institution), Personal fees, Non-financial support: Tesaro; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Calithera Biosciences; Research grant/Funding (institution): Biothera; Research grant/Funding (institution): OncoSec Medical; Honoraria (self), Research grant/Funding (institution), Personal fees, Non-financial support: Roche/Genentech; Research grant/Funding (institution): EMD Serono. C. Ferrario: Research grant/Funding (institution), Non-financial support, Other: F. Hoffmann-La Roche; Honoraria (self), Research grant/Funding (institution), Personal fees: Pfizer; Honoraria (self), Research grant/Funding (institution), Personal fees, Other: Bayer; Honoraria (self), Research grant/Funding (institution), Personal fees, Other: Novartis; Honoraria (self), Research grant/Funding (institution), Personal fees: AstraZeneca; Honoraria (self), Research grant/Funding (institution), Personal fees: Merck; Honoraria (self), Personal fees: Astellas Pharma; Honoraria (self), Personal fees: Genomic Health; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Casadian Therapeutics; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Janssen Oncology; Research grant/Funding (institution): Zymeworks. K. Punie: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Non-financial support: F. Hoffmann-La Roche; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution): Mundi Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Eli Lilly; Honoraria (institution), Advisory/Consultancy: Pierre Fabre; Honoraria (institution), Advisory/Consultancy: Vifor Pharma; Honoraria (institution), Advisory/Consultancy: Teva; Research grant/Funding (institution): Sanofi; Travel/Accommodation/Expenses: PharmaMar; Travel/Accommodation/Expenses: Novartis. F. Penault-Llorca: Honoraria (self), Research grant/Funding (institution), Personal fees: Myriad; Honoraria (self), Research grant/Funding (institution), Personal fees: Nanostring; Honoraria (self), Personal fees: Genomic Health; Honoraria (self), Personal fees: Novartis; Honoraria (self), Research grant/Funding (institution), Personal fees: AstraZeneca; Honoraria (self), Personal fees: Pfizer; Honoraria (self), Research grant/Funding (institution), Personal fees: Roche. S. Patel: Research grant/Funding (institution), Shareholder/Stockholder/Stock options, Non-financial support: F. Hoffmann-La Roche. A. Nguyen Duc: Research grant/Funding (institution), Full/Part-time employment, Non-financial support: F. Hoffmann-La Roche. M. Liste-Hermoso: Research grant/Funding (institution), Full/Part-time employment, Non-financial support: F. Hoffmann-La Roche. V. Maiya: Full/Part-time employment: F. Hoffmann-La Roche. L. Molinero: Research grant/Funding (institution), Shareholder/Stockholder/Stock options, Full/Part-time employment, Non-financial support: F. Hoffmann-La Roche. S.Y. Chui: Research grant/Funding (institution), Shareholder/Stockholder/Stock options, Full/Part-time employment, Non-financial support: F. Hoffmann-La Roche. E. Mittendorf: Advisory/Consultancy: Merck; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Sellas Life Sciences; Research grant/Funding (institution): GlaxoSmithKline.
159O - Prognostic value of tumour infiltrating lymphocytes in young triple negative breast cancer patients who did not receive adjuvant systemic treatment; by the PARADIGM study group
- Vincent M. De Jong (Amsterdam, Netherlands)
Abstract
Background
Uncertainty exists whether all young (< 40 years) patients with triple negative breast cancer (TNBC) require (neo)adjuvant chemotherapy. Increasing stromal tumour infiltrating lymphocytes (TIL) have been associated with improved outcome. However, limited data are available for young patients. We investigated whether TIL could aid in identifying a subgroup of young TNBC patients for whom de-escalating (neo)adjuvant chemotherapy could be considered.
Methods
All women <40 years, diagnosed with TanyN0M0 breast cancer between 1989 and 2000 were selected from the Netherlands Cancer Registry. We excluded women who received adjuvant systemic treatment. ER, PgR, and HER2 status were reassessed and TIL were scored for the triple negative (ER/PgR < 10% and HER2 negative) subset according to an established standard. Multivariable Cox regression was performed for overall (OS) and distant recurrence-free survival (DRFS). We used continuous TIL score, T-stage, tumour grade, histological subtype, and local treatment as covariates. For DRFS we censored patients at the time of a second primary tumour.
Results
We identified 481 TNBC patients, with a median age of 35 years (range 22 – 39). Most tumours were grade 3 (86%), pT1C (49%), median TIL score was 25% (IQR 5 – 70). In total, 122 DRFS events (25%) (89 metastases, 33 deaths), and 170 deaths (35%) occurred during a median of 16.2 and 21.2 years follow-up, respectively. In total, 110 (23%) patients developed a second primary tumour. OS at 10 and 15 years for patients with TIL ≥ 30% and <75% (n=127) was 80% (95% CI 73 - 87) and 76% (95% CI 69 – 84), DRFS was 84% (95% CI 78 – 91) and 83% (95% CI 76 – 90), respectively. For patients with ≥ 75% TIL (n=107) OS and DRFS at 10 and 15 year were 95% (95% CI 91 – 99), 93% (95% CI 89 – 99), 98% (95% CI 95 – 100) and 98% (95% CI 95 – 100), respectively. Risk of death or DRFS event reduced significantly for each 10% TIL increment (aHRs 0.83; 95% CI 0.79-0.88 and 0.74; 95% CI 0.68-0.80, respectively).
Conclusions
In young (<40 year), systemically untreated, N0, TNBC patients TIL provide important prognostic information. Subsequent investigations to de-escalate systemic therapy in a subgroup of young TNBC patients may be warranted.
Legal entity responsible for the study
The PARADIGM study group.
Funding
ZonMw A Sister's Hope Vrienden UMC Utrecht.
Disclosure
S. Michiels: Advisory/Consultancy, Statistical advice: IDDI; Advisory/Consultancy, Statistical advice: Janssen; Advisory/Consultancy, Statistical advice: Cilag; Advisory/Consultancy, Independant Data Monitoring Committee: Hexal; Advisory/Consultancy, Independent Data Monitoring Committee: Steba; Advisory/Consultancy, Independent Data Monitoring Committee: IQVIA; Advisory/Consultancy, Independent Data Monitoring Committee: Roche; Advisory/Consultancy, Independent Data Monitoring Committee: Sensorion; Advisory/Consultancy, Independent Data Monitoring Committee: Biophytis; Advisory/Consultancy, Independent Data Monitoring Committee: Servier; Advisory/Consultancy, Independent Data Monitoring Committee: Yuhan. S. Loi: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Meyers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Roche-Genentech; Research grant/Funding (institution): Puma Biotechnology; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Aduro Biotech; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: G1 Therapeutics. M. Kok: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Meyers Squibb; Research grant/Funding (institution): Roche-Genentech; Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Daiichi Sankyo. S. Linn: Research grant/Funding (self): ZonMw; Research grant/Funding (self): A Sister's Hope ; Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies, institutional non-financial support: AstraZeneca; Advisory/Consultancy, Non-remunerated activity/ies, institutional non-financial support: Cergentis; Advisory/Consultancy, Non-remunerated activity/ies, institutional non-financial support: IBM; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies, institutional non-financial support: Roche-Genentech; Research grant/Funding (institution), Non-remunerated activity/ies, institutional non-financial support: Tesaro; Research grant/Funding (institution), Non-remunerated activity/ies, institutional non-financial support: immunomedics; Non-remunerated activity/ies: Bayer; Research grant/Funding (institution), institutional non-financial support: Agendia; Research grant/Funding (institution): Eurocept-pharmaceuticals; Research grant/Funding (institution): Novartis. R.F. Salgado: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Bristol-Myers Squibb; Research grant/Funding (self), Travel/Accommodation/Expenses: Merck; Research grant/Funding (self): Puma Biotechnology; Travel/Accommodation/Expenses: AstraZeneca. All other authors have declared no conflicts of interest.
160O - Survival analysis of the randomized phase III GeparOcto trial comparing neoadjuvant chemotherapy (NACT) of iddEPC versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer, TNBC) (PM(Cb)) for patients (pts) with high-risk early breast cancer (BC)
- Andreas Schneeweiss (Heidelberg, Germany)
Abstract
Background
GeparOcto investigated dose-dense NACT with intense dose-dense epirubicin, paclitaxel, cyclophosphamide (iddEPC) and PM(Cb) in high-risk early BC. Primary endpoint pathological complete response (pCR; ypT0/is ypN0) was comparable in the whole cohort as well as in subgroups (Schneeweiss et al. EJC 2019). Here, we report the secondary endpoints invasive disease-free survival (iDFS) and overall survival (OS).
Methods
Pts were randomized (stratified by BC subtype, Ki67, lymphocyte-predominant BC) to receive 18 weeks of E (150 mg/m2) followed by P (225 mg/m2) followed by C (2000 mg/m2), each q2w for 3 cycles or weekly P (80 mg/m2) plus M (20 mg/m2) plus, in TNBC, Cb (AUC 1.5). HER2+ BC pts additionally received trastuzumab (6 [loading dose 8]mg/kg q3w) and pertuzumab (420 [840]mg q3w) with all P and C cycles. Adjuvant locoregional and endocrine therapy were given according to national guidelines. Secondary time-to-event endpoints were iDFS and OS.
Results
Between 12/2014 and 06/2016, a total of 961 pts were randomized and 945 started treatment (iddEPC n=470, PM(Cb) n=475). After a median follow-up of 47.0 (range 1.6-61.5) months, 75 iDFS events in iddEPC and 87 in PM(Cb) were reported. Overall, there was no difference in iDFS (hazard ratio PM(Cb) to iddEPC 1.16, 95%CI 0.85-1.59, p=0.3357) or OS (hazard ratio 0.90, 95%CI 0.58-1.40, p=0.6371) between both arms. In the subgroup of hormone-receptor (HR)+/HER2- BC, iDFS was significantly longer for iddEPC (4-year iDFS 62.5% with PM vs.77.9% with iddEPC; hazard ratio 2.11, 95%CI 1.08-4.10, p=0.0284), translating into an OS benefit (4-year OS 80.1% vs. 94.7%; hazard ratio 3.26, 95%CI 1.06-10.00, p=0.0388). There was no significant difference in survival in HER2+ or TNBC.
Conclusions
While there was no difference in survival following NACT with iddEPC or PM(Cb) for the entire cohort, the subgroup of HR+/HER2- BC significantly benefits from treatment with iddEPC. This supports the concept of effective therapy beyond pCR in luminal BC pts.
Clinical trial identification
NCT02125344.
Editorial acknowledgement
Dr. Bianca Lederer, GBG Forschungs GmbH.
Legal entity responsible for the study
GBG Forschungs GmbH.
Funding
Amgen, Roche, Teva.
Disclosure
A. Schneeweiss: Research grant/Funding (self): Celgene; Research grant/Funding (self): Roche; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Molecular Partner; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: AstraZeneca; Travel/Accommodation/Expenses: Celgene; Travel/Accommodation/Expenses: Roche; Honoraria (self): Roche; Honoraria (self): Celgene; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Tesaro; Honoraria (self): Lilly; Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (self), Medical writing grant: Roche. V. Möbus: Advisory/Consultancy: Roche; Advisory/Consultancy: Clovis; Advisory/Consultancy: Myelotherapeutics; Travel/Accommodation/Expenses: Celgene. H. Tesch: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis. C. Denkert: Shareholder/Stockholder/Stock options: Sividon Diagnostics; Honoraria (self): Novartis; Honoraria (self), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Daiichi Sankyo; Research grant/Funding (institution): Myriad Genetics; Licensing/Royalties: VMScope digital pathology software; Licensing/Royalties: Patent application: EP18209672 - cancer immunotherapy; Licensing/Royalties: Patent application EP20150702464 - therapy response; Licensing/Royalties: Patent application EP20150702464 - therapy response. C. Hanusch: Honoraria (self): Roche; Honoraria (self): Celgene; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Lilly. T. Link: Non-remunerated activity/ies: Pharma Mar; Non-remunerated activity/ies: Daiichi Sankyo; Honoraria (self), Non-remunerated activity/ies: MSD; Honoraria (self): Amgen; Honoraria (self), Non-remunerated activity/ies: Pfizer; Honoraria (self): Novartis; Honoraria (self): Teva; Honoraria (self): Tesaro; Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self), Non-remunerated activity/ies: Clovis; Non-remunerated activity/ies: Celgene. M. Untch: Honoraria (institution), Non-remunerated activity/ies: AbbVie; Honoraria (institution), Non-remunerated activity/ies: Amgen GmbH; Honoraria (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (institution): BMS; Honoraria (institution), Non-remunerated activity/ies: Celgene GmbH ; Honoraria (institution), Non-remunerated activity/ies: Daiichi Sankyo ; Honoraria (institution), Non-remunerated activity/ies: Eisai GmbH; Honoraria (institution): Lilly Deutschland; Honoraria (institution), Non-remunerated activity/ies: Lilly Int.; Honoraria (institution), Non-remunerated activity/ies: MSD Merck; Honoraria (institution), Non-remunerated activity/ies: Mundipharma; Honoraria (institution), Non-remunerated activity/ies: Myriad Genetics ; Honoraria (self), Non-remunerated activity/ies: Odonate; Honoraria (institution), Non-remunerated activity/ies: Pfizer GmbH; Honoraria (self): PUMA Biotechnology; Honoraria (institution), Non-remunerated activity/ies: Roche Pharma AG; Honoraria (institution), Non-remunerated activity/ies: Sanofi Aventis Deutschland GmbH; Honoraria (institution), Non-remunerated activity/ies: TEVA Pharmaceuticals Ind Ltd; Honoraria (institution), Non-remunerated activity/ies: Novartis; Honoraria (institution): Pierre Fabre; Honoraria (institution), Non-remunerated activity/ies: Clovis Oncology. C. Jackisch: Honoraria (self): Celgene; Honoraria (self): Roche. J-U. Blohmer: Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): MSD Oncology; Honoraria (self): Novartis/Pfizer; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): SonoScape. P.A. Fasching: Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy: Roche; Research grant/Funding (institution): BionTech; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Celgene; Speaker Bureau/Expert testimony: Daiichi-Sankyo; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Advisory/Consultancy: Macrogenics; Advisory/Consultancy: Eisai; Advisory/Consultancy: Puma; Research grant/Funding (institution): Cepheid; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: AstraZeneca; Speaker Bureau/Expert testimony: Amgen. J. Huober: Honoraria (self): Lilly; Honoraria (self): Roche; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self): Pfizer; Travel/Accommodation/Expenses: AbbVie; Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Celgene; Research grant/Funding (self): Hexal; Honoraria (self): MSD; Travel/Accommodation/Expenses: Daiichi. K.E. Rhiem: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Pfizer. K. Lübbe: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Genomic Health; Honoraria (self): Pfizer. S. Loibl: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Amgen; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Celgene; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (institution), Advisory/Consultancy: Seattle Genetics; Honoraria (institution), Advisory/Consultancy: PriME/ Medscape; Speaker Bureau/Expert testimony: Chugai; Research grant/Funding (institution): Teva; Research grant/Funding (institution): Vifor; Honoraria (institution), Research grant/Funding (institution): Daiichi-Sankyo; Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (institution), Advisory/Consultancy: Samsung; Advisory/Consultancy: Eirgenix; Advisory/Consultancy: BMS; Advisory/Consultancy: Puma; Honoraria (institution): MSD; Research grant/Funding (institution): Immunomedics; Licensing/Royalties, Immunsignature in TNBC: EP14153692.0 pending. All other authors have declared no conflicts of interest.
Invited Discussant LBA11, 159O and 160O
- Sherko Kümmel (Essen, Germany)
Q&A and live discussion
- Javier Cortés (Barcelona, Spain)
LBA12 - PALLAS: A randomized phase III trial of adjuvant palbociclib with endocrine therapy versus endocrine therapy alone for HR+/HER2- early breast cancer
- Erica L. Mayer (Boston, United States of America)
Abstract
Background
Palbociclib (P) added to endocrine therapy (ET) improves progression-free survival in hormone receptor positive (HR+)/HER-2 negative (HER2-) metastatic breast cancer. The global PALLAS trial (NCT02513394) was designed to determine if the addition of two years of P to adjuvant ET improves invasive disease-free survival (iDFS) over ET alone in patients (pts) with HR+/HER2- early-stage breast cancer.
Methods
In this phase III open-label trial, pts with stage II-III HR+/HER2- breast cancer were randomized to receive either 2 years of P with adjuvant ET, or ET alone. Eligible pts were within 12 months of diagnosis and 6 months of initiating adjuvant ET. The primary objective was to compare invasive disease-free survival (iDFS) between arms; secondary objectives include other recurrence endpoints and safety, as well as quality of life, adherence, and translational science. The study had 85% power to detect a 25% improvement in iDFS (0.75 hazard ratio [HR]). Interim analyses (IA) were predefined in the protocol; IA2 was triggered when 67% of events were observed.
Results
5,760 pts (median age 52 years) were randomized and included in the analysis; 1,013 (17.6%) had stage IIA disease and 4,729 (82.1%) stages IIB/III. 4,754 (82.5%) had received prior chemotherapy. At IA2, after a median follow-up of 23.7 months (351 events), iDFS was similar between the two arms, with 3-year iDFS of 88.2% for P and ET, and 88.5% for ET alone (HR 0.93, 95% confidence interval 0.76-1.15), crossing a pre-specified futility boundary. No benefit from P was observed within clinicopathologic subgroups. Grade 3 or 4 neutropenia was more common with P (61.3% vs 0.4%) but febrile neutropenia was uncommon (1.0%). Other all-grade toxicities occurring more often with P included leukopenia, fatigue, thrombocytopenia, anemia, upper respiratory tract infection, and alopecia. 42.2% of pts discontinued P prior to the planned 2 year duration, primarily due to adverse events.
Conclusions
Within the PALLAS trial, at IA2, two years of adjuvant palbociclib with ET did not improve iDFS compared to ET alone. Ongoing long-term follow-up and additional clinical and translational analyses will explore the effect of P in this patient population.
Clinical trial identification
NCT02513394.
Legal entity responsible for the study
Alliance Foundation Trials, LLC; Austrian Breast and Colorectal Cancer Study Group (ABCSG).
Funding
Pfizer, Inc.
Disclosure
E.L. Mayer: Advisory/Consultancy, Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Myriad; Research grant/Funding (institution): Roche/Genentech. M.I. Gnant: Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Celgene; Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: Invectys; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Puma; Travel/Accommodation/Expenses: NanoString; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Medison; Travel/Accommodation/Expenses: Lifebrain; Spouse/Financial dependant: Sandoz. A. DeMichele: Honoraria (self), Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Menarini; Advisory/Consultancy: Context Therapeutics; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Calithera. M. Martin: Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Puma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Amgen; Advisory/Consultancy: Taiho Oncology; Honoraria (self), Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: Lilly; Advisory/Consultancy: Daiichi-Sankyo; Honoraria (self), Advisory/Consultancy: Pfizer. A. Prat: Honoraria (self), Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Honoraria (self): BMS; Honoraria (self), Research grant/Funding (institution): Daiichi-Sankyo; Advisory/Consultancy: Puma; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Research grant/Funding (institution): Nanostring Technologies; Research grant/Funding (institution): Boehringer; Research grant/Funding (institution): Sysmex Europa GmbH; Research grant/Funding (institution): Medica Scientia Inno Research; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Astellas Pharma. G. Rubovszky: Honoraria (self), Advisory/Consultancy: Pfizer. G. Pfeiler: Advisory/Consultancy: Amgen; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Lilly; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: MSD. E.P. Winer: Advisory/Consultancy: Carrick; Advisory/Consultancy: Jounce; Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy: GSK; Advisory/Consultancy, Officer/Board of Directors: Leap; Advisory/Consultancy: InfiniteMD; Advisory/Consultancy: Gi Theraputics; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Novartis; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Syros. Z. Nowecki: Honoraria (self): Samsung; Honoraria (self): Roche. S. Loibl: Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Seattle Genetics; Honoraria (institution): PriME/Medscape; Honoraria (self): Chugai; Research grant/Funding (institution): Teva; Research grant/Funding (institution): Vifor; Honoraria (institution), Research grant/Funding (institution): Daiichi-Sankyo; Advisory/Consultancy: Lilly; Advisory/Consultancy: Samsung; Advisory/Consultancy: Eirgenix; Advisory/Consultancy: BMS; Advisory/Consultancy: Puma; Honoraria (institution): MSD; Honoraria (institution): Immunomedics; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca. O. Metzger: Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Breast Cancer Research Foundation; Research grant/Funding (institution): Cascadian Therapeutics; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Komen for the Cure; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy, Travel/Accommodation/Expenses: Group Oncoclinicas. D. Fumagalli: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Servier; Research grant/Funding (institution): Tesaro. K. Puyana Theall: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. All other authors have declared no conflicts of interest.
161O - Randomized preoperative window of opportunity (WOO) study with the CDK4/6 inhibitor abemaciclib in early breast cancer (EBC) patients and differential gene expression pathway analyses with palbociclib
- Monica Arnedos (Villejuif, France)
Abstract
Background
In our previous WOO study short-term palbociclib caused a profound inhibition in proliferation. Due to the different pattern of CDK target inhibition, we conducted a similar WOO trial with abemaciclib to determine its antiproliferative effect and to assess differences in GE array pathway analyses with palbociclib.
Methods
Untreated EBC patients (n=105) were randomized 3:1 to abemaciclib 150mg twice daily for 14 days vs. no treatment. FFPE and frozen samples were taken at baseline and at surgery. Primary objective was antiproliferative response defined as natural logarithm of Ki67 expression at day 15<1. Immunostainings (Ki67, RB, pRB, p16, Cyclin D1, Cyclin E1, Cyclin E2, TILs, CD8+/FOXP3 ratio) and gene expression (GE) arrays were performed pre- and post-treatment. Pooled GE pathway analysis with GE arrays from our WOO trial with palbociclib and comparisons between drugs were performed.
Results
In the ABC-POP trial, abemaciclib led to significant differences as compared to control in antiproliferative effect (71 vs. 8%; p <0.001) and changes in Ki67 (p<0.0001), pRB (p<0.0001), Cyclin D1 (p=0.047) and Cyclin E2 (p<0.0001) by IHC. No significant predictive biomarkers were identified. Abemaciclib had significant effect on change from baseline in 63 genes mostly associated with cell cycle and proliferation. No genes were significantly associated with abemaciclib antiproliferative effect. In the pooled (N=168) GE pathway analysis with patients from ABC-POP and from the trial with palbociclib, CDK4/6 inhibition was associated to significant effect on E2F, G2M and mitotic spindle pathways. No differential effect on GE pathways was observed between abemaciclib and palbociclib.
Conclusions
Short-term pre-operative abemaciclib was associated to significant antiproliferative effect as well as a change in cell cycle biomarkers like pRb, Cyclin D1 and Cyclin E2 by IHC and by GE array. Pooled GE pathway analyses with palbociclib treated patients showed significant effect on cell cycle pathways although no significant differences were seen between the two CDK4/6 inhibitors. Further analyses with the pooled GE arrays will be presented.
Clinical trial identification
NCT02831530.
Legal entity responsible for the study
Gustave Roussy Cancer Campus.
Funding
Eli Lilly.
Disclosure
M. Arnedos: Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Seattle Genetics; Honoraria (self), Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Eli Lilly. J. Adam: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: Bayer. S. Michiels: Advisory/Consultancy: IDDI; Advisory/Consultancy: Janssen Cilag. F. André: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (institution): Eli Lilly; Honoraria (institution), Research grant/Funding (institution): Pfizer; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Daiichi; Honoraria (institution): Roche. All other authors have declared no conflicts of interest.
Invited Discussant LBA12 and 161O
- Serena Di Cosimo (Milan, Italy)
Q&A and live discussion
- Javier Cortés (Barcelona, Spain)