Abstract 1428
Background
HER2 blockade in combination with chemotherapy (CT) remains the treatment of choice for patients with early HER2+ BC, irrespective of ER status. Patients with HER2+ early BC co-expressing ER may benefit from HER2 blockade in combination with endocrine therapy (ET) and new targeted agents. Elderly patients benefit from HER2 blockade as much as younger ones but they have higher risks of adverse events, mostly induced by the CT partner, making de-escalation of CT appealing. Recent data have elucidated cyclin-dependent kinases 4 and 6 (CDK4/6) as key therapeutic targets functioning downstream of both ER and HER2 pathways suggesting CDK4/6 inhibitors like Pal may be ideal partners for ET in this context. Pre-clinical and clinical data suggest that a gene signature of functional loss of Retinoblastoma (RBsig) might predict sensitivity to CT vs CDK4/6i in ER+/HER2+ early BC. The TOUCH hypothesis is that neoadjuvant therapy with Pal + ET + dual HER2 blockade may be more active in patients with ER+/HER2+ RBsig LOW early BC while those with RBsig HIGH may require CT.
Trial design
TOUCH is an open-label, multicenter, randomized phase 2 neoadjuvant trial. 144 patients ≥65 years with ER+/HER2+ primary BC will be randomized (1:1) to dual HER2 blockade (5 doses T+P) + either Pal (125 mg/d po; 21 of 28d x 4 cycles) + L (daily x 16 weeks), or Pac (80 mg/m2 iv, d1,8,15 q28 days x 4 cycles), before surgery. RBsig (HIGH vs LOW) will be determined centrally on mandatory pre-treatment biopsies. Baseline geriatric assessment includes G8, Instrumental Activity of Daily Living, Charlson comorbidity index. The primary objective is to explore the interaction between RBsig and treatment activity assessed by pathological complete response (pCR). Exact logistic regression will test RBsig by treatment interaction (2-sided a=.05) and estimate odds ratios (OR) for pCR. The sample size provides 86% power, assuming an overall pCR rate of 26%, and OR = 2.4 vs OR = 0.11 for RBsig LOW vs HIGH. Accrual began April 2019.
Clinical trial identification
NCT03644186.
Editorial acknowledgement
Legal entity responsible for the study
International Breast Cancer Study Group.
Funding
Pfizer, Roche.
Disclosure
L. Biganzoli: Advisory / Consultancy, consultant and in an advisory role: AstraZeneca; Advisory / Consultancy, consultant and in an advisory role: Celgene; Advisory / Consultancy, consultant and in an advisory role: Eisai; Advisory / Consultancy, consultant and in an advisory role: Genomic Health; Advisory / Consultancy, consultant and in an advisory role: Ipsen; Advisory / Consultancy, consultant and in an advisory role: Lilly; Advisory / Consultancy, consultant and in an advisory role: Novartis; Advisory / Consultancy, consultant and in an advisory role: Pfizer; Advisory / Consultancy, consultant and in an advisory role: Pierre Fabre; Advisory / Consultancy, consultant and in an advisory role: Roche; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Genomic Health; Research grant / Funding (institution): Novartis. E. Brain: Honoraria (self), receipt of honoraria or consultation fees: Roche; Honoraria (self), receipt of honoraria or consultation fees: Pfizer; Honoraria (self), receipt of honoraria or consultation fees: AstraZeneca; Honoraria (self), receipt of honoraria or consultation fees: BMS; Honoraria (self), receipt of honoraria or consultation fees: Celgene; Honoraria (self), receipt of honoraria or consultation fees: Clinigen; Honoraria (self), receipt of honoraria or consultation fees: Hospira; Honoraria (self), receipt of honoraria or consultation fees: Janssen; Honoraria (self), receipt of honoraria or consultation fees: Mylan; Honoraria (self), receipt of honoraria or consultation fees: OBI Pharma; Honoraria (self), receipt of honoraria or consultation fees: Puma; Honoraria (self), receipt of honoraria or consultation fees: Samsung. L. Malorni: Research grant / Funding (self), research funding and consulting fees: Pfizer. All other authors have declared no conflicts of interest.
Resources from the same session
4401 - Real-world effectiveness of first-line palbociclib + letrozole for metastatic breast cancer 4 years post approval in the US
Presenter: Jonathan Kish
Session: Poster Display session 2
Resources:
Abstract
5876 - Palbociclib-Fulvestrant (PALBO-FUL) and Everolimus -Exemestane (EVE-EXE) for Second line Hormonal Treatment (HT) of Metastatic Breast Cancer (MBC) with Lobular Histology: a Propensity Score Matched Analysis of a Multicenter ‘Real-World’ Patients (pts) Series.
Presenter: Armando Orlandi
Session: Poster Display session 2
Resources:
Abstract
3587 - Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC)
Presenter: E Dees
Session: Poster Display session 2
Resources:
Abstract
5696 - Final results of the STEM trial: SFX-01 in the Treatment and Evaluation of ER+ Her2- Metastatic breast cancer (mBC)
Presenter: Sacha Howell
Session: Poster Display session 2
Resources:
Abstract
1475 - Alpelisib (ALP) + Fulvestrant (FUL) in Hormone-Receptor Positive (HR+), Human Epidermal Growth Factor Receptor-2–Negative (HER2–) Advanced Breast Cancer (ABC): Subgroup Analysis by Presence of Visceral Metastasis (VM) in the SOLAR-1 Trial
Presenter: Mario Campone
Session: Poster Display session 2
Resources:
Abstract
2549 - Phase 1 Dose Escalation Study of a Selective Androgen Receptor Modulator RAD140 in Estrogen Receptor Positive (ER+), HER2 Negative (HER2-) Breast Cancer (BC)
Presenter: Erika Hamilton
Session: Poster Display session 2
Resources:
Abstract
3787 - A Phase I study of XZP-3287, a novel oral CDK4/6 Inhibitor, administered on a continuous dosing schedule, in patients with advanced solid tumours
Presenter: Binghe Xu
Session: Poster Display session 2
Resources:
Abstract
4835 - Phase-I dose-escalation and expansion study of the PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors
Presenter: Huiping Li
Session: Poster Display session 2
Resources:
Abstract
5083 - Phase 2 study of DHP107 (Liporaxel®, oral paclitaxel) in first-line, HER2 negative recurrent/metastatic breast cancer (OPTIMAL study, NCT03315364)
Presenter: Jin-Hee Ahn
Session: Poster Display session 2
Resources:
Abstract
2674 - Multicenter Phase I Trial of Trastuzumab Emtansine (T-DM1) in Combination with Non-Pegylated Liposomal Doxorubicin (NPLD) in HER2[+] Metastatic Breast Cancer (MBC). THELMA Study
Presenter: Elena López-Miranda
Session: Poster Display session 2
Resources:
Abstract