Case Study Suggests Ixazomib Potential Chemotherapy-Free Biological Treatment for Breast Cancer

A new case report details a complete pathological response to a 3-month combination therapy of ixazomib, bendamustine, and dexamethasone (IBd) in a patient with multiple myeloma and an incidental cT1b (9 mm) hormone receptor(HR)–positive breast cancer lesion.

The 68-year-old patient also showed no signs of disease relapse during follow-up. This case report is the first to describe such a clinical outcome in breast cancer following the combination of therapies, the researchers explained in Tumori.

To better understand the potential antitumoral properties of ixazomib in breast cancer and assess the synergism between ixazomib and bendamustine, the investigators carried out in vitro experiments using 2 HR-positive breast cancer cell lines.

“We found no synergistic interaction between the 2 drugs, while ixazomib alone showed an antiproliferative effect against tumoral cells, suggesting that this drug has been responsible for tumor regression in our case,” they wrote.

Ixazomib is a second-generation protease inhibitor available for relapsed or refractory multiple myeloma. Past research shows the treatment has potential as an antitumoral agent in preclinical solid tumor models, such as breast cancer cell lines. Ixazomib can be administered orally.

A combination of an immunomodulatory drug, a proteasome inhibitor, and steroids is often the first line of treatment for patients with newly diagnosed multiple myeloma. However, the condition still has a 5-year survival rate of around 48.5%, the researchers wrote.

In the current case study, the patient was referred to a Hematology Unit at a hospital in Italy in 2017 due to suspected multiple myeloma. The patient was not deemed a candidate for autologous stem cell transplant and was enrolled in a clinical trial that tested ixazomib as a part of different induction therapy regimens in multiple myeloma.

“Per protocol, she was randomized to receive nine 28-day induction cycles of IBd (ixazomib 4 mg on days 1, 8, 15; bendamustine 75 mg/m2 IV on days 1 and 8; dexamethasone 40 mg on days 1, 8, 15, and 22, followed by ixazomib maintenance therapy for up to 2 years,” the authors wrote.

A February 2017 basal PET/CT revealed an abnormal fluorodeoxyglucose uptake in the patient’s right breast. A breast cancer management team recommended conservative surgery due to the small tumor size and favorable subtype. This intervention was rescheduled to 12 weeks after the bioptical diagnosis, during which the patient began IBd induction therapy.

The day before the scheduled surgery, the lesion could no longer be identified.

“The patient did not undergo surgery, and hormone-blocking therapy with letrozole was started. At regular follow-up visits (the latest performed in 2022 with the patient still undergoing letrozole treatment), no evidence of [breast cancer] relapse or progression was found,” theauthors wrote.

When researchers tested the drugs that had led to complete remission on invasive HR-positive breast cancer cell lines, they found no synergistic interaction between ixazomib and bendamustine. Additional tests revealed ixazomib inhibits cell proliferation in a dose-dependent fashion. Because of this, the researchers hypothesized it’s not unlikely that ixazomib alone, and not in combination with bendamustine, “was solely responsible for tumor regression in our patient.”

However, although both HR-positive breast cancer cell lines showed sensitivity to the treatment, there was high variability in in vitro efficacy.

“This aspect is likely due to unknown molecular determinants of variability amongst HR-positive breast cancer cell lines, to be addressed in future; larger cell line panels; or other tumor models,” they noted.

Overall, the researchers said ixazomib could hold potential as a chemotherapy-free biological treatment.

“Our findings, in line with other preclinical works, suggest that a window-of-opportunity well-designed clinical trial in the neoadjuvant treatment of HR+ BC may be needed,” they concluded.

Reference

Dameri M, Garlaschi A, Cuccarolo P, et al. Complete pathological response of hormone receptor positive invasive breast cancer in a patient with multiple myeloma treated with ixazomib. Tumori. Published online June 2, 2023. doi:10.1177/03008916231176586