Anastrozole Combo Yields High Clinical Benefit in HR+/HER2+ Breast Cancer

In a conversation with CancerNetwork^®, Amy Tiersten, MD, spoke to positive efficacy findings from the phase 1/2 ASPIRE trial (NCT03304080), assessing anastrozole (Arimidex) plus palbociclib (Ibrance), trastuzumab (Herceptin), and pertuzumab (Perjeta) in hormone receptor (HR)–positive, HER2-positive metastatic breast cancer that were presented at the 2023 San Antonio Breast Cancer Symposium (SABCS).

Tiersten, professor of medicine and clinical director of Breast Medical Oncology at Mount Sinai Hospital, said that the experimental regimen produced a clinical benefit rate of 97% (95% CI, 83%-100%), thus meeting the trial’s primary end point. Other data highlighted an objective response rate of 73% (95% CI, 54%-88%) in the experimental arm, which included partial responses in 60% of patients and complete responses in 4%. Additionally, the combination didn’t have any new safety signals, with the toxicity profile being comparable with prior reports of each individual agent.

Following these results, Tiersten said she was interested in initiating a randomized phase 2 trial comparing anastrozole in combination with a CDK4/6 inhibitor and trastuzumab or pertuzumab with chemotherapy plus trastuzumab and pertuzumab, the current standard of care in HR-positive, HER2-positive metastatic breast cancer.

Transcript:

We exceeded our primary end point expectation. The clinical benefit rate was 97%, which was really fabulous. No patients had progressive disease as their best response, and the duration of response was quite long. Toxicity was sort of what would be expected with the known toxicity profiles of the individual agents. Those are the main important data points to take home.

I would love to compare this [combination] to standard frontline therapy for [patients with] hormone receptor–positive, HER2-positive metastatic breast cancer. Currently, the standard of care in the frontline setting is chemotherapy with trastuzumab and pertuzumab. I would foresee the potential for perhaps a phase 2 randomized trial comparing anastrozole with a CDK4/6 inhibitor and trastuzumab or pertuzumab vs a standard chemotherapy such as a taxane plus trastuzumab and pertuzumab. I’d like to look into proceeding with that.

Reference

Patel R, Cascetta K, Klein P, et al. A multicenter, phase I/II trial of anastrozole, palbociclib, trastuzumab, and pertuzumab in hormone receptor (HR)-positive, HER2-positive metastatic breast cancer (ASPIRE). Presented at the 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX; abstract RF02-01.