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
4317 - Prognostic factors analysis of 343 patients with adenocarcinoma of esophagogastric junction
Presenter: Yixun Lu
Session: Poster Display session 2
Resources:
Abstract
4099 - Effects of preoperative preparation time on efficacy of neoadjuvant chemotherapy (SOX) in patients with advanced gastric cancer
Presenter: Xinxin Wang
Session: Poster Display session 2
Resources:
Abstract
3769 - The prognostic value of higher absolute lymphocyte counts for patients with surgically resected non-advanced gastric cancer
Presenter: Se Jun Park
Session: Poster Display session 2
Resources:
Abstract
1718 - Trastuzumab and pertuzumab added to neoadjuvant chemoradiotherapy in resectable HER2+ esophageal adenocarcinoma patients: an update on survival and predictive biomarkers in the TRAP study
Presenter: Charlotte Stroes
Session: Poster Display session 2
Resources:
Abstract
5403 - Interim analysis of a phase II trial of perioperative chemotherapy plus avelumab in esophagogastric and gastric adenocarcinoma
Presenter: Thierry Alcindor
Session: Poster Display session 2
Resources:
Abstract
591 - Evaluation of the introduction of primary G-CSF prophylaxis to the FLOT chemotherapy regimen.
Presenter: Kelly-Marie Crampton
Session: Poster Display session 2
Resources:
Abstract
1402 - Subgroup analyses of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with 2 and 4 courses of cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) as neoadjuvant chemotherapy for locally advanced gastric cancer
Presenter: Tsutomu Hayashi
Session: Poster Display session 2
Resources:
Abstract
3743 - HER2 Copy Number as Predictor of Disease-Free Survival in HER2-Positive Resectable Gastric Cancer
Presenter: Zimin Liu
Session: Poster Display session 2
Resources:
Abstract
2032 - Effect of neoadjuvant chemotherapy on the Programmed Death-1 pathway in esophageal and gastric cancer
Presenter: Maria Svensson
Session: Poster Display session 2
Resources:
Abstract
4304 - A user-friendly nomogram to predict relapse-free survival (RFS) in western patients with resected gastric cancer (GC)
Presenter: Massimiliano Salati
Session: Poster Display session 2
Resources:
Abstract