Photo Credit: Marcela Ruth Romero
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 with pCR rates up to 65%. HER2-directed antibody-drug conjugates (ADCs), such as T-DM1 and T-DXd, have shown remarkable efficacy in metastatic BC and are now being evaluated in the neoadjuvant setting,” Junjie Li, MD, PhD, from Fudan University Cancer Hospital, China, commented1.
The phase 2 FASCINATE-N (NCT05582499) evaluated SHR-A1811, a third-generation HER2-directed ADC, 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. They were randomly assigned to receive SHR-A1811 alone (n=87), SHR-A1811 plus the oral tyrosine kinase inhibitor pyrotinib (n=88), or the four-drug regimen of PCbHP (n=90) for 24 weeks, followed by surgery. The primary endpoint included pCR rates between the three 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 three arms. An exploratory analysis of tumor regression was conducted by recording baseline tumor diameters with breast MRI after every two cycles. “Similar retraction rates were observed across the three arms, with approximately 55% decrease after cycle two and a 75% decrease after cycle 4,” Dr. Li said. Subgroup analysis of pCR showed comparable efficacy across all three treatment arms.
In conclusion, Dr. Li explained the clinical value of the trial, “the standard four-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 be a backbone for future treatment.”
Medical writing support was provided by Kulsoom Abdul.
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