Home > Oncology > SABCS 2024 > HER2-positive Breast Cancer > Encouraging results of neoadjuvant SHR-A1811 in the treatment of HER2-positive breast cancer

Encouraging results of neoadjuvant SHR-A1811 in the treatment of HER2-positive breast cancer

Presented by
Dr Junjie Li, Fudan University Cancer Hospital, China
Conference
SABCS 2024
Trial
Phase 2, FASCINATE-N
Doi
https://doi.org/10.55788/2cb481b1
In the phase 2 FASCINATE-N trial, neoadjuvant SHR-A1811 showed similar pathologic complete response (pCR) rates to the standard 4-drug regimen, with a tolerable safety profile in patients with HER2-positive breast cancer (BC).

“Currently, the standard 4-drug regimen of paclitaxel, carboplatin, trastuzumab, and pertuzumab [PCbHP] is the preferred choice according to NCCN guidelines, with pCR rates up to 65%. HER2-directed antibody-drug conjugates [ADCs], such as trastuzumab emtansine [T-DM1] and trastuzumab deruxtecan [T-DXd], have shown remarkable efficacy in metastatic BC and are now being evaluated in the neoadjuvant setting,” Dr Junjie Li (Fudan University Cancer Hospital, China) commented [1]. “SHR-A1811 is a third-generation HER2-directed ADC composed of trastuzumab, a cleavable linker, and a topoisomerase I inhibitor payload, offering high membrane permeability and potent cell-killing activity.” In a global phase 1 trial, SHR-A1811 has shown efficacy in 76.3% of heavily pre-treated HER2-positive BC [2].

The prospective, randomised, open-label, phase 2 FASCINATE-N trial (NCT05582499) evaluated SHR-A1811 in the neoadjuvant treatment of HER2-positive BC. The 265 participants with early-stage or locally advanced BC were HER2-positive and had an ECOG performance status of 0 or 1. Dr Li and colleagues used multi-omic characteristics to stratify the participants into different subtypes, aiming to investigate the efficacy of precision-based targeted therapies versus standard neoadjuvant chemotherapy. The participants were randomised to receive SHR-A1811 alone (n=87), SHR-A1811 plus the oral tyrosine kinase inhibitor pyrotinib (n=88), or the 4-drug regimen of PCbHP (n=90) for 24 weeks, followed by surgery. The primary endpoint included pCR rates between the 3 arms.

In the overall population, the pCR rate was 63.2% in the SHR-A1811 arm, 62.5% in the SHR-A1811 plus pyrotinib arm, and 64.4% in the PCbHP arm, with no significant differences observed between the 3 arms. An exploratory analysis of tumour regression was conducted by recording baseline tumour diameters with breast MRI after every 2 cycles. “Similar retraction rates were observed across the 3 arms, with approximately a 55% decrease after cycle 2 and a 75% decrease after cycle 4,” Dr Li said. Subgroup analysis of pCR showed comparable efficacy across all 3 arms. Notably, participants with baseline stage II tumours achieved a pCR rate of 88.8% in the SHR-A1811 arm, while those with primary stage III disease achieved a pCR rate of 64.6% in the combination arm. “These results warrant further investigation,” said Dr Li.

In conclusion, Dr Li explained the clinical value of the trial: “The standard 4-drug regimen is highly effective and identifying a better regimen with an improved pCR rate is challenging. In the era of ADCs that show comparable efficacy, SHR-A1811 might serve as a backbone for future treatment.”


    1. Li J, et al. HER2-Directed Antibody-Drug Conjugate SHR-A1811 in the Neoadjuvant Treatment of HER2-Positive Early Breast Cancer: A Prospective, Randomized, Open-Label, Phase 2 Trial. GS1-04, SABCS 2024, 10–13 December, San Antonio, TX, USA.
    2. Yao H, et al. J Clin Oncol. 2024;42(29):3453-3465.

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