A phase II trial of the pan‐HER inhibitor poziotinib, in patients with HER2‐positive metastatic breast cancer who had received at least two prior HER2‐directed regimens: results of the NOV120101‐203 trial. Issue 12 (7th November 2018)

• Record Type: Journal Article
• Authors: Park, Yeon Hee; Lee, Kyung‐Hun; Sohn, Joo Hyuk; Lee, Keun Seok; Jung, Kyung Hae; Kim, Jee‐Hyun; Lee, Ki Hyeong; Ahn, Jin Seok; Kim, Tae‐Yong; Kim, Gun Min; Park, In Hae; Kim, Sung‐Bae; Kim, Se Hyun; Han, Hye Sook; Im, Young‐Hyuck; Ahn, Jin‐Hee; Kim, Jung‐Yong; Kang, Jahoon; Im, Seock‐Ah
• Is Part Of: International journal of cancer. Volume 143:Issue 12(2018)
• Page Start: 3240
• Page End: 3247
• Publication Date: 2018-11-07
• Subjects: HER2 -- poziotinib -- breast cancer; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31651
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Although the introduction of human epidermal growth factor receptor (HER)2‐directed therapy including trastuzumab, pertuzumab, lapatinib and trastuzumab emtansine (T‐DM1) in the treatment of HER2‐positive metastatic breast cancers (mBCs) favorably changed the natural history of this disease, most cases of HER2‐positive mBC will eventually progress. Poziotinib is an oral pan‐HER kinase inhibitor showing potent activity through irreversible inhibition of these kinases. This open‐label, multicenter phase II study was designed to evaluate the efficacy and safety of poziotinib monotherapy in patients with HER2‐positive mBC who had progressed from more than two HER2‐directed therapies. Patients received 12 mg poziotinib once daily on a 14‐day on/7‐day off schedule. Progression‐free survival (PFS) as the primary endpoint, the objective response rate (ORR), overall survival (OS) and safety were evaluated. From April 2015 to February 2016, 106 patients were enrolled in the trial from seven institutes in South Korea. They had a median age of 51 years (range 30–76) and had received a median of four prior therapies including two HER2‐directed therapies for advanced or metastatic cancers. The median follow‐up duration was 12 months. The median PFS was 4.04 months (95% confidence interval [CI], 2.94–4.40 months), and median overall survival has not been reached. The most common treatment‐related adverse events were (total/grade ≥3) diarrhea (96.23%/14.15%), stomatitis (92.45%/12.26%) and rashes (63.21%/3.77%). Poziotinib showed meaningful activity in these heavily treated HER2‐positive mBCs. Diarrhea and stomatitis were the major toxicities. Biomarker studies analyzed are warranted to support further evaluation of this treatment in such cases. Abstract : What's new? Targeting human epidermal growth factor receptor 2 (HER2) has revolutionized treatment of HER2‐positive cancers but rapid resistance development causes significant clinical problems. In this phase II study, the authors tested poziotinib, a new oral pan‐HER inhibitor, in patients with metastatic breast cancer after two prior HER2‐directed therapies. Treatment with poziotinib achieved on average a progression‐free survival of ~4 months with relatively mild side effects (skin rash and diarrhoea), an encouraging result for patients with repeated treatment failure.