Phase II study of the PI3K inhibitor BKM120 in patients with advanced or recurrent endometrial carcinoma: a stratified type I–type II study from the GINECO group
| العنوان: | Phase II study of the PI3K inhibitor BKM120 in patients with advanced or recurrent endometrial carcinoma: a stratified type I–type II study from the GINECO group |
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| المؤلفون: | Florence Joly, Frank Priou, S Roche-Forestier, C Foa, Benoit You, I.L. Ray-Coquard, Michel Fabbro, Anne Floquet, C. Roemer-Becuwe, Frédéric Selle, Laure Favier, P-E Heudel, A. Lesoin, Elsa Kalbacher, Alain Lortholary, A. Arnaud, Jérôme Meunier, Marie-Christine Kaminsky, Dominique Berton-Rigaud, Youssef Tazi, Isabelle Treilleux |
| المصدر: | British Journal of Cancer |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Morpholines, Aminopyridines, Phases of clinical research, Antineoplastic Agents, PI3K inhibitor, Biology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, PI3K Inhibitor BKM120, Recurrence, Internal medicine, medicine, Carcinoma, Humans, buparlisib/BKM120, Adverse effect, Aged, Phosphoinositide-3 Kinase Inhibitors, Aged, 80 and over, Middle Aged, targeted therapy, medicine.disease, Rash, Chemotherapy regimen, Endometrial Neoplasms, Clinical trial, Treatment Outcome, 030104 developmental biology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, metastatic endometrial cancer, Toxicity, Disease Progression, Clinical Study, Female, Neoplasm Recurrence, Local, medicine.symptom, Carcinoma, Endometrioid |
| الوصف: | Backround: Patients with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of the pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma. Methods: This phase II, multicentre, single-arm, double strata (histological low grade (LG) or high grade (HG)) open-label study enrolled patients with histologically confirmed advanced or recurrent endometrial carcinoma who had received not more than one prior chemotherapy regimen. Patients received initially BKM120 100 mg tablets once daily. Primary end points were proportion of patients free of progression at 2 months (HG strata) or at 3 months (LG strata), objective response rate (ORR), and safety. Results: A total of 40 patients were enrolled, of whom 16 patients had received BKM120 at 100 mg. Because of high toxicities (cutaneous rash (54%), depressive events (47%), and anxiety (40%), the IDMC has proposed to stop recruitment at 100 mg and to continue the clinical trial with a lower dose of 60 mg per day. In addition, 24 patients (median age 67 years old) were newly enrolled (14 in the LG strata and 10 in the HG strata). Rate of nonprogression at 2 months in the HG strata was 70% and at 3 months was 60% in the LG strata. Median progression-free survival (PFS) for all patients is 4.5 months (CI 95% 2.8–6.1), and the median PFS for LG strata is 8.3 months compared with 3.8 months for the HG strata. No response was reported. At 60 mg per day, the most commonly reported treatment-related adverse events (AEs) were hyperglycaemia (58%), cognitive (31%), digestive (28%), hepatic liver functions (26%), and rash (23%). The most commonly reported treatment-related grade ⩾3 AEs were HTA (17%), hyperglycaemia (17%), and increased alanine aminotransferase (24%). Five patients (21%) stopped BKM120 for toxicity. Conclusions: The BKM120 was associated with an unfavourable safety profile and minimal antitumour activity in monotherapy in advanced or recurrent endometrial carcinoma. The clinical trial was stopped before end of recruitment for toxicity. |
| تدمد: | 1532-1827 0007-0920 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::09a05bdc8f53201f5704b8efa24a8d76 https://doi.org/10.1038/bjc.2016.430 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....09a05bdc8f53201f5704b8efa24a8d76 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15321827 00070920 |
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