Abstract 1479
Background
Immune checkpoint inhibition (ICI) is synergistic with HER2-directed therapy in pre-clinical models. Clinically, pembrolizumab (K)-mediated ICI plus HER2-directed therapy with trastuzumab (H) is safe and demonstrated modest activity in H-resistant HER2-positive (HER2+) metastatic breast cancer. Because ICI may confer more robust activity when administered earlier in the course of disease, HER2-directed therapy with ICI administered in the curative-intent, treatment-naive setting may allow for de-escalation of cytotoxic backbones; confer life-long, tumor-specific immunity; and ultimately, improve cure rates. Moreover, the synergy of H and K with paclitaxel (T) may overcome the need for dual HER2-blockade with H plus pertuzumab (P). This randomized, multicenter, phase II, open-label trial, will evaluate the efficacy and safety of neoadjuvant THP vs THP-K vs TH-K (NCT03747120).
Trial design
174 patients (pts) ≥18y with previously untreated, clinical stage II-III, HER2+ breast cancer will be randomized 1:1:1 to one of the 3 arms, stratified by clinical nodal status (positive vs. negative) and hormone receptor status (positive vs. negative). In arm A, pts receive THP: T at 80 mg/m2 weekly for 12 weeks, H day 1 at 8 mg/Kg (loading dose) and then 6 mg/Kg every 3 weeks x 3 doses, P day 1 at 840 mg (loading dose) and then 420 mg/Kg every 3 weeks x 3 doses (THP). In arm B, pts receive THP plus K day 1 at 200mg (flat dose) and then every 3 weeks x 3 doses (THP-K). In arm C, pts receive TH-K. Definitive surgery is 3-6 weeks after the last dose of T. After surgery, pts are treated per the treating physician’s discretion including HER2-directed therapy and radiotherapy per local clinical standards. Pts whose tumors are hormone-receptor positive will receive hormone therapy per local standard-of-care. The primary end point is pathologic complete response (pCR) rate in the breast and axilla (ypT0/Tis ypN0). Secondary end points include pCR rate by ypT0ypN0 and ypT0/Tis, residual cancer burden index, event free survival, breast conserving surgery rate, safety and overall survival. Exploratory correlative studies will characterize potential immune biomarkers predictive of efficacy and/or toxicity.
Clinical trial identification
NCT03747120.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Breast Cancer Research Foundation, Merck & Co.
Disclosure
H.L. McArthur: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Spectrum Pharmaceuticals; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: Immunomedics; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Genentech; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Genomic Health; Research grant / Funding (institution): ZIOPHARM Oncology; Travel / Accommodation / Expenses: Puma Biotechnology. J.H.S. Leal: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche/Genentech; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca. D.B. Page: Honoraria (self): Novartis; Advisory / Consultancy, Research grant / Funding (self): Merck Sharp & Dohme; Advisory / Consultancy: Syndax; Advisory / Consultancy: Nektar; Advisory / Consultancy: NanoString Technologies; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Puma Biotechnology; Speaker Bureau / Expert testimony: Genentech/Roche; Research grant / Funding (institution), Travel / Accommodation / Expenses: MedImmune; Speaker Bureau / Expert testimony: Philips Healthcare. A. Bardia: Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Radius Health; Advisory / Consultancy, Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): Innocrin; Advisory / Consultancy, Research grant / Funding (institution): Biothernostics Inc.; Advisory / Consultancy: Spectrum Pharma; Advisory / Consultancy: Taiho; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Daiichi Pharma. L. Spring: Advisory / Consultancy: Novartis; Advisory / Consultancy: Lumicell; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Research grant / Funding (institution): Tesaro. R.K. Basho: Advisory / Consultancy: Puma Biotech; Advisory / Consultancy: Heron Therapeutics. S. Verma: Advisory / Consultancy: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Puma; Advisory / Consultancy: Novartis; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Mylan. All other authors have declared no conflicts of interest.
Resources from the same session
3963 - Robot-assisted natural orifice specimen extraction surgery for radical resection of colorectal cancer
Presenter: Zhengchuan Niu
Session: Poster Display session 2
Resources:
Abstract
3989 - Bevacizumab as adjuvant treatment for colon cancer: Updated results from the AVANT phase III Study by the GERCOR Group
Presenter: Thierry André
Session: Poster Display session 2
Resources:
Abstract
4741 - Real world data on adjuvant chemotherapy for high-risk stage II colorectal cancer – the role of tumor side
Presenter: Camila Araujo de Carvalho
Session: Poster Display session 2
Resources:
Abstract
4973 - Oncological Outcome and Safety of Bevacizumab (BV) Therapy in Patients with Occlusive Colon Cancer and Self-Expandable Metal Stents (SEMS)
Presenter: Vilma Pacheco-Barcia
Session: Poster Display session 2
Resources:
Abstract
2295 - Active chronic hepatitis B increases the risk of liver metastasis of colorectal cancer- a retrospective clinical study of 7187 consecutive cases of newly diagnosed colorectal cancer
Presenter: Lei Zhao
Session: Poster Display session 2
Resources:
Abstract
3845 - Comprehensive Evaluation of Recurrence Risk (CERR) Score for Colorectal Liver Metastases: Development and Validation
Presenter: Wei Ye
Session: Poster Display session 2
Resources:
Abstract
1976 - BRAF-mutated colorectal metastases: what is the benefit of liver surgery? Results from a cohort of 91 patients.
Presenter: Sahir Javed
Session: Poster Display session 2
Resources:
Abstract
2688 - The smallest colorectal liver metastasis size as a prognosis factor after laparoscopic liver resection
Presenter: Baptiste Cervantes
Session: Poster Display session 2
Resources:
Abstract
4961 - Validation of GAME score risk groups in resected colorectal cancer liver metastases and the prognostic relevance of KRAS, NRAS and BRAF mutation analysis
Presenter: Berta Martin-Cullell
Session: Poster Display session 2
Resources:
Abstract
5295 - Predictive factors and survival outcomes with stereotactic body radiation therapy in treatment of oligometastases in colorectal cancer
Presenter: Vibhay Pareek
Session: Poster Display session 2
Resources:
Abstract