Conflicting results have been reported on the impact of HER2-low expression on the efficacy of CDK4/6 inhibitors in hormone receptor-positive (HR+) metastatic breast cancer. No data are yet available in the neoadjuvant setting. We investigated the efficacy of letrozole-palbociclib (LETPAL) combination as neoadjuvant treatment according to HER2 expression in an exploratory analysis of the NeoPAL study (UCBG104, NCT02400567).
NeoPAL was a randomised, parallel, non-comparative phase II study which assigned pts with HR+ HER2-, Prosigna®-defined luminal B or A and node-positive, stage II-III breast cancer to LETPAL or chemotherapy. Primary endpoint was residual cancer burden (RCB 0-I rate). Secondary endpoints included clinical response, proliferation-based markers, and safety. HER2 low status was centrally reviewed according to the ASCO/CAP guidelines.
40/53 patients treated in the LETPAL arm were evaluable for this substudy: HER2-low (n=20), HER2-0 (n=20). Luminal B molecular subtype was predominant in both groups (95% and 80% respectively) with a baseline high risk Prosigna® ROR score in 88.9% and 82.6% of patients, respectively. After 4 months of LETPAL, RCB 0-I was observed in one patient of each group and pathological complete response rates were 2.5% and 0% in the HER2-low and HER2-0 subgroups respectively. A 0-I PEPI score was observed in 4 patients in each group. Interestingly, the HER2 status switched (either way) in 7 out of 28 analysable matched samples (25%). LETPAL induced a decrease in the ROR score at surgery in a similar proportion in both groups: 68.4% and 60.0% of tumors switched from high or intermediate risk to low risk in the HER2-low and HER2-zero groups, respectively. All exploratory p values were >0.1. Strikingly similar results were observed in the chemotherapy arm.
Neoadjuvant palbociclib activity in combination with letrozole does not seem to be influenced by the tumor’s HER2 status (low versus zero).
NCT02400567.
Unicancer.
Has not received any funding.
J. Frenel: Financial Interests, Personal, Advisory Board: Pfizer, Novocure, Pierre Fabre, Eisai, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: GSK, Amgen; Financial Interests, Institutional, Advisory Board: Exact Science, Lilly, Daiichi Sankyo, AstraZeneca, Clovis Oncology; Financial Interests, Institutional, Invited Speaker: Novartis, MSD; Financial Interests, Invited Speaker: AstraZeneca, Seagen, MSD, Daiichi; Non-Financial Interests, Principal Investigator: Novartis, Lilly, AstraZeneca, Pfizer, Daiichi, MSD. A. Vincent-Salomon: Financial Interests, Personal, Invited Speaker, Lectures honorarium: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Ibex, Roche; Financial Interests, Personal, Invited Speaker: MSD, Roche; Financial Interests, Personal, Stocks/Shares: Ibex; Financial Interests, Institutional, Research Grant: AstraZeneca, Ibex; Financial Interests, Institutional, Funding: Owkin. P. Heudel: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Novartis, Seagen, Lilly; Financial Interests, Institutional, Invited Speaker: AstraZeneca. F.P. Duhoux: Financial Interests, Institutional, Advisory Board: Roche, Pfizer, AstraZeneca, Lilly, Novartis, Amgen, Daiichi Sankyo, Pierre Fabre, Gilead, Seagen, MSD; Financial Interests, Institutional, Invited Speaker: Novartis, Pfizer, MSD, Roche, MSD, Boehringer Ingelheim, Pfizer, Novartis, Lilly, AbbVie, Seagen, Gilead, AstraZeneca, Menarini, Immutep; Financial Interests, Institutional, Expert Testimony: Seagen, Novartis, MSD. G. Emile: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Novartis, Roche. F. Dalenc: Non-Financial Interests, Principal Investigator: Roche, AstraZeneca, Gilead, Novartis. J. Ferrero: Financial Interests, Personal, Advisory Board: Pfizer, Exact sciences, Novartis; Financial Interests, Personal, Invited Speaker: Lilly. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Pierre Fabre, Orion, Sanofi, Rappta, Cellectis, Isis/servier; Financial Interests, Institutional, Invited Speaker: Exact Sciences, Pfizer, Seagen, Lilly, AstraZeneca, MSD, Roche Genentech, BMS, Puma, AstraZeneca, Orion, Sanofi, Pfizer; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Invited Speaker, ESMO symposium: Gilead; Financial Interests, Institutional, Advisory Board, scientific board: Elsan; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM; Non-Financial Interests, Principal Investigator, H2020 funding: European Commission. P.H. Cottu: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer, Lilly; Financial Interests, Personal, Expert Testimony: Roche; Financial Interests, Institutional, Invited Speaker: Daiichi, Lilly, Gilead; Financial Interests, Institutional, Funding: Novartis. All other authors have declared no conflicts of interest.