Randomized phase II clinical trial of pioglitazone plus chemotherapy versus chemotherapy alone in patients with metastatic breast cancer.

83 Background: Breast carcinoma is the second cause of mortality between female cancers and metastasis is the main contributing factor to the mortality in patients with breast cancer. Optimal management for visceral metastatic breast cancer (MBC) remains unknown. In this study we aimed to assess if adding pioglitazone to chemotherapy regimen can improve response in patients with MBC. Methods: This double-blind randomized clinical trial enrolled women 18 years or older with visceral MBC either previously treated with adjuvant therapy or currently are undergoing different lines of endocrine and chemotherapy regimens. The main objective of this study is to compare treatment efficacy in patients with visceral MBC taking chemotherapy plus Pioglitazone (n = 30) versus chemotherapy in addition to placebo (n = 30) over three months. The efficacy evaluated by change in radiologic response defined by the proportion of patients with stable or partial/complete radiologic response to those experienced disease progression based on Revised Recist Guideline ver (1.1). Results: Combination of pioglitazone and chemotherapy led to higher complete radiologic response (7.4% vs.0%) stable disease status (66·7% vs. 53·6%) and lower progression (22·2% vs. 35·7%) rates, however the differences were not statistically significant (P = 0.24). Clinical benefit rate (CBR, proportion of patients with complete response, partial response, or stable disease) was 77.8% in pioglitazone group vs. 64.3% in control group (p = 0.27). Subgroup analysis revealed higher efficacy but not statistically significant among diabetic woman, who had hormone-receptor–positive tumor. Furthermore, patients treated with Taxan +/-Carboplatin agents had significantly higher stable disease status, lower progression rate and higher complete response rate than the placebo group (P = 0·03). Conclusions: This is the first reported randomized clinical trial on the efficacy of pioglitazone in patients with visceral MBC which demonstrated safety and improvement of response in the subgroup of Taxan / Carboplatin chemotherapy regimen. These findings are in agreement with previous results of in vitro preclinical studies. Clinical trial information: IRCT20180124038493N1.