Puma Biotechnology, Inc. (NASDAQ: PBYI) has just released the results of an exciting clinical trial investigating the potential of alisertib to treat endocrine-resistant advanced breast cancer. Alisertib is a powerful and reversible inhibitor of aurora kinase A, which can disrupt mitosis and cause tumor cell death. Published in JAMA Oncology, the trial studied the effects of alisertib either alone or in combination with fulvestrant. This novel approach to treating breast cancer could bring hope to many patients and their families.
The Translational Breast Cancer Research Consortium conducted a Phase II randomized clinical trial to evaluate the efficacy of alisertib when combined with fulvestrant in postmenopausal women with endocrine-resistant, HER2–negative metastatic breast cancer. Of the 91 evaluable patients, baseline characteristics were evenly distributed between the two trial arms; however, more patients in the alisertib plus fulvestrant arm had been previously treated with chemotherapy in the metastatic setting. Moreover, all of the participants in both arms of the trial had been previously treated with CDK 4/6 inhibitors, with 37% in the alisertib alone arm and 57.8% in the alisertib plus fulvestrant arm having also been given everolimus.
The trial results showed promising results for alisertib alone and alisertib plus fulvestrant. Of the 46 evaluable patients in the alisertib alone arm, nine had partial responses, giving an overall response rate of 19.6%. The median duration of response was 15.1 months, and the 24-week clinical benefit rate was 41.3%. Moreover, the median progression-free survival (PFS) was estimated to be 5.6 months. Similarly, of the 45 evaluable patients in the alisertib plus fulvestrant arm, nine had a response with one complete response and eight partial responses, resulting in an overall response rate of 20.0%. The median duration of response was 8.5 months, and the 24-week clinical benefit rate was 28.9%. The estimated median PFS was 5.4 months. These results demonstrate the potential of alisertib as a treatment option for patients.
Patients receiving alisertib alone in the trial experienced neutropenia (43.4%), leukopenia (17.4%), and anemia (19.6%) as the most common grade 3 or higher adverse events. Meanwhile, in the arm of the trial combining alisertib with fulvestrant, neutropenia (42.2%), leukopenia (31.1%), lymphopenia (15.6%), fatigue (11.1%), and anemia (8.9%) were the most frequently reported grade 3 or higher adverse events.
The need for new treatments for ER-positive HER2-negative metastatic breast cancer that are effective in patients previously treated with CDK 4/6 inhibitors is still pressing. Thus, the promising results of the Phase II randomized clinical trial of alisertib in the setting of endocrine and CDK 4/6 inhibitor resistant metastatic breast cancer is particularly encouraging. Not only did the investigational targeted therapy demonstrate clinical activity, but it also had a tolerable safety profile. Dr. Tufia C. Haddad, co-leader of Platform and Digital Innovation at the Mayo Clinic Comprehensive Cancer Center, is hopeful that the continued development of alisertib in this patient population will prove to be beneficial.
We are thrilled with the outcomes of the TBCRC041 trial, which showed the effectiveness of alisertib in patients with ER-positive HER2-negative metastatic breast cancer. Alisertib has a unique and promising mechanism of action, making it a great tool to address CDK 4/6 resistance that can be treated with an aurora kinase inhibitor. We are eager to further develop alisertib for use in additional clinical trials for ER-positive HER2-negative breast cancer. Alan H. Auerbach, Chairman, Chief Executive Officer and President of Puma, echoed this sentiment.
About Puma Biotechnology
Puma Biotechnology, Inc. is a biopharmaceutical company dedicated to the development and commercialization of innovative products to improve cancer treatment. In 2017, their drug PB272 (neratinib, oral) was approved by the U.S. Food and Drug Administration for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer after trastuzumab-based therapy. This drug is marketed in the United States as NERLYNX® (neratinib) tablets. In February 2020, NERLYNX was also approved for the treatment of advanced or metastatic HER2-positive breast cancer. Additionally, NERLYNX was granted marketing authorization by the European Commission in 2018 for the extended adjuvant treatment of adult patients with early stage hormone receptor-positive HER2-overexpressed/amplified breast cancer.
In September 2022, Puma took a groundbreaking step forward in the fight against cancer by signing an exclusive license agreement to develop and commercialize alisertib – a selective, small molecule, orally administered inhibitor of aurora kinase A. This innovative anti-cancer drug is set to revolutionize the treatment of small cell lung cancer and breast cancer, as Puma strives to make a real difference in the lives of those affected by these diseases.