Dr Li on Neoadjuvant SHR-A1811 in HER2+ Breast Cancer

“The pCR rate is around [63.2%], but I mention that because now the neoadjuvant treatment for HER2-positive breast cancer—the standard therapy—is quite efficacious.”

Junjie Li, MD, associate chief physician, Fudan University Shanghai Cancer Center, discusses efficacy findings for the HER2-directed antibody-drug conjugate (ADC) SHR-A1811 in the neoadjuvant treatment of patients with HER2-positive breast cancer, based on findings from the phase 2 FASCINATE-N trial (NCT05582499) presented at the 2024 San Antonio Breast Cancer Symposium (SABCS).

The FASCINATE-N trial included 3 arms, Li notes, where patients were randomly assigned 1:1:1 to receive SHR-A1811 monotherapy; SHR-A1811 plus pyrotinib; or PCbHP (nab-paclitaxel [Abraxane], carboplatin, trastuzumab [Herceptin] and pertuzumab [Perjeta]). Of note, efficacy was observed with all 3 treatment regimens, Li says. Since standard neoadjuvant treatment has shown activity in patients with early HER2-positive breast cancer, he emphasizes, a pathologic complete response (pCR) rate of 63.2% (95% CI, 53.9%-71.8%) with SHR-A1811 monotherapy (n = 87) is notable. In the 95% CI, 55.3%-72.8%). In the SHR-A1811 plus pyrotinib arm (n = 88), the pCR rate was 62.5% (95% CI, 53.2%-71.1%). In the PCbHP arm (n = 90), the pCR rate was 64.4% (95% CI, 55.3%-72.8%).

Regarding safety, the rates of grade 3/4 treatment-related adverse effects were 44.8% for SHR-A1811 monotherapy, 71.6% for SHR-A1811 plus pyrotinib, and 38.8% for PCbHP. TRAEs led to dose reductions in 10.3%, 17.2%, and 13.3% of patients, respectively. TRAEs led to treatment discontinuation in 5.7%, 29.9%, and 16.7% of patients, respectively.

Li also notes that researchers are testing treatment de-escalation of 4 cycles instead of the typical 6 or 8 cycles in patients with low-risk HER2–positive breast cancer, such as those with T1N1 or T2N0 disease. He explains that the FASCINATE-N trial focused on enrolling patients with high tumor burden, which resulted in approximately 90% of patients with lymph node positivity and 70% of patients with stage III disease. Notably, with the higher tumor burden in this patient population, the 63.2% pCR rate was promising, he says.