Clinical experience with Vemurafenib in pretreated melanoma (MEL): The results of open label multi center study from Turkey.
Bildiriler > Özet Bildiri
Yazarlar: Ismail Celik, Nil Molinas Mandel, Erhan GÖKMEN, Olcun Umit Unal, Alper Sevinc, Hasan Senol Coskun, Suleyman Buyukberber, Huseyin Abali, Mustafa Ozguroglu, Gungor Utkan, Mahmut Gumus, Bahadir Pekin, Asligul Kendirci
Journal of Clinical Oncology, , , Uluslararası, Özet Bildiri, Wos, cilt 33, ss e20085-e20085
DOI: 10.1200/jco.2015.33.15_suppl.e20085
Özet
e20085 Background: Activating mutations in BRAF gene are present in 40-60% of metastatic MEL patients (pts). VEM is an inhibitor of kinase domain in mutated BRAF. In previous trials VEM had been shown to increase PFS and OS. This is an open label, multicenter study to allow pts to access to VEM prior to approval in Turkey. Methods: A total of 111 pts accessed VEM as a part of expanded access program. The reassessment data to confirm response were not available due to safety rules of Turkish Local Regulatory Authority. Point estimates of survival were reported and subgroup analysis according to LDH, ECOG status and presence of brain metastases was performed. Overall and anatomic site specific side effects were recorded and analyzed using descriptive statistical methods (PFS/OS estimated using Kaplan-Meier method). Results: The median age of pts were 52 (18-91) years. At baseline, 54% had stage M1c disease, 9.9% had an ECOG PS ≧2 and 46% had elevated LDH; 77.5% of pts had received prior systemic therapy, 9.9% received prior ipilimumab, and 19.8% radiotherapy for brain metastases. Median PFS and OS were 5.7 (95% CI 4.8-6.9) and 9.7 (95% CI 7.4-13.6) months, respectively. Poor prognostic factors for OS, included increased lactate dehydrogenase, intracranial metastasis and high ECOG scores. In 30.6% of pts at least one grade ≥ 3 adverse effect was observed. Squamous cell carcinoma occurred in 5.4% of patients. AEs requiring dose reduction occurred in 11% of pts, and 2 pts (1.8%) experienced events leading to VEM withdrawal. Conclusions: This study confirms that VEM is a safe and effective treatment option. For several groups often not included in clinical trials including pts with previously treated brain metastases, ECOG PS ≧ 2 to 3 had benefit. The PFS was consistent across most of the subgroups (Table:1) and overall survival was lower in subgroups with markers of poor prognosis than in the overall population. These results were consistent with Global Safety Study results in terms of survival (1). 1. Larkin J, Del Vecchio M, Ascierto PA, et al. Vemurafenib in patients with BRAF(V600) mutated metastatic melanoma: an open-label, multicentre, safety study. Lancet Oncol. 2014 Apr; 15(4):436-44. Clinical trial information: NCT01307397.