Novel agent ‘highly efficient’ in HER2-positive breast cancer
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Key takeaways:
- Researchers reported an encouraging pathologic complete response rate with SHR-A1811 monotherapy.
- No treatment-related deaths occurred during the study.
SAN ANTONIO — The novel antibody-drug conjugate SHR-A1811 exhibited promising antitumor activity as neoadjuvant treatment for patients with HER2-positive breast cancer, according to data presented at San Antonio Breast Cancer Symposium.
The agent also exhibited a manageable safety profile.
“This is the first study to report a third-generation HER2-directed antibody-drug conjugate in the neoadjuvant treatment of HER2-positive breast cancer,” Jun-Jie Li, MD, of Fudan University Shanghai Cancer Center, said during a presentation. “SHR-A1811 monotherapy is highly efficient and well tolerated.”
Background and methods
Standard neoadjuvant regimens for HER2-positive breast cancer include trastuzumab (Herceptin, Genentech), pertuzumab (Perjeta, Genentech) and chemotherapy.
A prior phase 1 study showed SHR-A1811 (Jiangsu Hengrui Pharmaceuticals) had antitumor activity among patients with heavily pretreated HER2-expressing or mutated advanced solid tumors. Results showed an objective response rate of 59.9%, with higher ORRs among patients with HER2-positive breast cancer (76.3%) and HER2 low-expressing breast cancer (60.4%).
No data exists on the efficacy and safety of HER2-directed antibody-drug conjugates (ADC) alone or in combination with tyrosine kinase inhibitors in the neoadjuvant setting.
The randomized phase 2 FASCINATE-N trial included 265 patients with early-stage or locally advanced HER2-positive breast cancer. All patients had primary tumor size of at least 2 cm, left ventricular ejection fraction of at least 55%, and ECOG performance of 0 or 1.
Researchers randomly assigned patients 1:1:1 to one of three regimens.
One group (n = 87) received 4.8 mg/kg SHR-A1811 via IV once every 3 weeks for eight cycles. A second group (n = 88) received 4.8 mg/kg SHR-A1811 via IV once every 3 weeks plus 240 mg oral pyrotinib (Jiangsu Hengrui Pharmaceuticals) once daily for eight cycles. A third group (n = 90) received PCbHP, a regimen that consisted of 100 mg/m2 nab-paclitaxel (days 1, 8 and 21 of 28-day cycles), carboplatin area under the curve 1.5 (days 1, 8 and 21 of 28-day cycles), trastuzumab (initial dose, 8 mg/kg IV; subsequent doses, 6 mg/kg IV every 3 weeks) and pertuzumab (initial dose, 840 mg IV; subsequent doses, 420 mg IV every 3 weeks) for six cycles.
Pathologic complete response (pCR) in the intention-to-treat population served as the primary endpoint.
The majority (70%) of the cohort had stage III disease and 45% had hormone receptor-positive disease.
At SABCS, Li reported data related to antitumor activity and safety.
Results, next steps
Results showed pCR rates of 63% with SHR-A1811 monotherapy, 62% with SHR-A1811 plus pyrotinib, and 66% with PCbHP.
Subgroup analysis of patients with hormone receptor-positive breast cancer showed pCR rates of 44% with SHR-A1811 monotherapy, 44% with SHR-A1811 plus pyrotinib, and 54% with PCbHP.
Among patients with hormone receptor-negative breast cancer, results showed pCR rates of 76% with SHR-A1811 monotherapy, 76% with SHR-A1811 plus pyrotinib, and 75% with PCbHP.
Grade 3 or higher adverse events occurred more frequently with SHR-A1811 plus pyrotinib (72%) than SHR-A1811 monotherapy (45%) or PCbHP (34%).
One patient who received SHR-A1811 monotherapy developed grade 2 interstitial lung disease, and 9% of individuals who received SHR-A1811 with pyrotinib developed grade 3 diarrhea.
No treatment-related deaths occurred during the study.
“The standard four-drug regimen is highly effective, with a pCR rate around 65%,” Li said. “With comparable efficacy, SHR-A1811 might serve as a backbone and combination with targeted therapies. [In] my opinion, maybe one can substitute for four, and then add more.”
References:
- Li J, et al. Abstract GS1-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-13, 2024; San Antonio.
- Yao H, et al. J Clin Oncol. 2024;doi:10.1200/JCO.23.02044.
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Li J, et al. Abstract GS1-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-13, 2024; San Antonio.
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