Abstract CT311: A randomized, open-label phase 2 study of efatutazone and erlotinib as second- or third-line therapy for non-small cell lung cancer (NSCLC)
Authors: Oton Ana B. , Cho Byoung Chul , Ahn Myung-Ju , Kim Sang-We , Subramanian Kirushnakumar , Desai Chirag , Shuster Dale , Goldberg Terri , Zahir Hamim , Dutta Dipen , Chen Shuquan , Roemeling Richard Von , Pawel Joachim von 
Published: May 2015

Abstract
Introduction: Efatutazone is a potent, highly selective peroxisome proliferator-activated receptor gamma (PPARγ) agonist active in preclinical cancer models, including NSCLC. In phase 1 studies, efatutazone showed anticancer activity and a manageable safety profile. An in vitro study combining a PPARγ agonist and an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), similar to erlotinib, showed an increase in the antiproliferative effects of the EGFR-TKI in NSCLC cells (Lee et al. Lung Cancer. 2006). This study evaluated the safety and efficacy of efatutazone added to erlotinib as second- or third-line NSCLC therapy.
Methods: Patients from Germany, India, Korea, and the United States with NSCLC that progressed after first-line platinum therapy and no more than 1 additional therapy were stratified by Eastern Cooperative Oncology Group (ECOG) status (0/1 vs 2) and randomized 1:1 to efatutazone + erlotinib (E+E) or erlotinib alone (E). Efatutazone (0.5 mg) was administered orally, twice daily; erlotinib (150 mg) was administered orally, once daily. Treatment was given continuously in the absence of disease progression, withdrawal of consent, or unacceptable toxicity. The primary end point was progression-free survival (PFS) assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Results: Characteristics of the 90 randomized patients for E+E and E treatment groups, respectively, were: median age, 60 vs 61 years; male sex, 75.6% vs 55.6%; never smoker, 31.1% vs 46.7%; ECOG status 0/1, 91.1% vs 91.1%; and partial response (PR) as best response to prior therapy, 15.6% vs 26.7%. PFS was not different between treatments (hazard ratio [HR], 0.93; P = 0.79) with median PFS of 4.1 vs 2.8 months in the E+E vs E arms, respectively. The objective response rate was also similar at 20.5% vs 20.0% for E+E and E, respectively. Overall survival was not statistically different between the E+E vs E arms (median, 7.6 vs 11.4 months; HR, 1.20; P = 0.46). The most frequent adverse events (≥ 25%) or those of special interest for E+E and E, respectively, were anemia (36.4% vs 6.7%), diarrhea (40.9% vs 40.0%), peripheral edema (38.6% vs 2.2%), decreased appetite (40.9% vs 22.2%), dermatitis acneiform (34.1% vs 20.0%), rash (25.0% vs 31.1%), and pleural effusion (22.7% vs 0%).Conclusions: Efatutazone did not improve the efficacy of erlotinib as second- or third-line therapy for NSCLC. Adverse events associated with efatutazone in combination with erlotinib were related to anemia and fluid retention as expected with this drug class.
Citation Format: Ana B. Oton, Byoung Chul Cho, Myung-Ju Ahn, Sang-We Kim, Kirushnakumar Subramanian, Chirag Desai, Dale Shuster, Terri Goldberg, Hamim Zahir, Dipen Dutta, Shuquan Chen, Richard Von Roemeling, Joachim von Pawel. A randomized, open-label phase 2 study of efatutazone and erlotinib as second- or third-line therapy for non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT311. doi:10.1158/1538-7445.AM2014-CT311