Abstract 41P
Background
HER2-low status is a predictive factor for high-potency anti-HER2 therapy in metastatic hormonal receptor-positive breast cancer (HR+ MBC). However, the impact of HER2-low status on hormonal therapy remains uncertain. We aimed to explore the effect of HER2-low and HER-2 zero in HR+ MBC patients treated with first-line aromatase inhibitors (AI) with or without CDK 4/6 inhibitors (CDK4/6i).
Methods
Post-menopausal patients or pre-menopausal patients who received ovarian function suppression diagnosed with HR+ MBC between 2017-2022 and treated with first-line AI with or without CDK4/6 inhibitors from six tertiary hospitals in Thailand were retrospectively reviewed. Comparison of progression-free survival (PFS) and overall survival (OS) were made in unadjusted cohorts and after adjustment of baseline characteristics (age, ECOG, de novo metastasis, treatment-free interval, visceral metastasis, and number of metastatic site) with stabilized inverse probability treatment weighting (sIPTW).
Results
Of 504 patients, 219 (43.5%) had HER2-low, and 285 (56.5%) had HER2-zero. The median age at diagnosis of advanced breast cancer was 60 (range 22-84) in HER2-low cohort and 61 (range 18-89) in HER2-zero cohort. CDK4/6i+AI was administered to 52.5% and 43.9% of patients in the HER2-low and HER-2 zero cohorts, respectively. 72% of patients received ribociclib and 28% received palbociclib. The median follow-up time was 29 months (18-38) for CDK4/6i+AI and 35 months (20.5-53) for AI. The data cut-off date was September 30, 2023. Outcomes of AI with or without CDK4/6i in HER2-low and HER-2 zero metastatic HR+ breast cancer Table: 41P
| Unadjusted | sIPTW | |||||||
| HER2-low | CDK4/6i+AI (n=115) | AI(n=104) | HR | p | CDK4/6+AI(n=109) | AI(n=106) | HR | p |
| mPFS(m) | 25.2 | 22.3 | 0.91 | 0.56 | 25.5 | 18 | 0.68 | 0.03 |
| mOS(m) | 49.3 | 51.3 | 0.88 | 0.59 | 52.4 | 37.9 | 0.55 | <0.01 |
| HER2-zero | CDK4/6+AI(n=125) | AI(n=160) | HR | p | CDK4/6+AI(n=129) | AI(n=162) | HR | p |
| mPFS(m) | 26.1 | 14.9 | 0.64 | <0.01 | 25.5 | 12.8 | 0.62 | <0.01 |
| mOS(m) | 55.7 | 42.3 | 0.76 | 0.12 | 45.9 | 38.4 | 0.67 | 0.08 |
| CDK4/6+AI | HER2-low(n=115) | HER2-zero(n=125) | HR | p | HER-2low(n=115) | HER2-zero(n=125) | HR | p |
| mPFS(m) | 25.2 | 26.1 | 1.03 | 0.88 | 26.6 | 25.6 | 0.93 | 0.69 |
| mOS(m) | 49.3 | 55.7 | 0.83 | 0.44 | 52.4 | 55.7 | 0.72 | 0.16 |
| AI | HER2-low(n=104) | HER2-zero(n=160) | HR | p | HER2-low(n=104) | HER2-zero(n=159) | HR | p |
| mPFS(m) | 22.3 | 14.9 | 0.74 | 0.04 | 20.4 | 16.2 | 0.86 | 0.31 |
| mOS(m) | 51.3 | 42.3 | 0.75 | 0.07 | 43.9 | 47 | 0.97 | 0.86 |
Conclusions
CDK4/6i+AI yielded better outcomes compared to AI alone in both HER2-low and HER2-zero metastatic HR+ breast cancer. HER2-low status did not affect prognosis in patients receiving either CDK4/6i+AI or AI alone.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
P. Sunpaweravong: Financial Interests, Personal, Advisory Board: Roche, Eisai, BMS, AstraZeneca, MSD, Pfizer, Amgen; Financial Interests, Personal, Invited Speaker: Novartis, BMS, Mundipharma, Bayer; Financial Interests, Institutional, Local PI: Roche, Novartis, AstraZeneca, MSD. S. Ithimakin: Financial Interests, Personal, Invited Speaker: Novartis, Zuellig Pharma, AstraZeneca. T. Dejthevaporn: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Zeullig Pharma, Novartis, AstraZeneca, Dr. Reddy, Roche; Financial Interests, Institutional, Local PI, paid as a fee for service delivered: Roche; Financial Interests, Institutional, Local PI, paid as a fee for service delivered through institution: Pfizer. All other authors have declared no conflicts of interest.