Abstract
Objectives
Vemurafenib tolerability was assessed in a large, open-label, multicentre study in patients with BRAF V600 mutated advanced melanoma. We investigated safety, tolerability and efficacy of vemurafenib in Spanish patients participating in that study.
Methods
Patients with previously treated or treatment-naive, unresectable stage IIIC or stage IV, BRAF V600 mutation-positive melanoma received vemurafenib 960 mg twice daily until disease progression, unacceptable toxicity, withdrawal of consent or death. The primary endpoint was safety; secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).
Results
301 Spanish patients were included, 70 % with M1c disease, 22 % with brain metastases and 51 % with prior systemic therapy for metastatic disease. Most frequent adverse events included fatigue (48 %), arthralgia (45 %), rash (41 %), photosensitivity (34 %) and skin neoplasms (21 %). Grade 3/4 adverse events occurred in 156 patients (52 %), including cutaneous squamous cell carcinoma (including keratoacanthoma; 16 %), fatigue (6 %) and arthralgia (5 %). The ORR was 28 % (95 % CI 23–34 %). Responses occurred in patients with brain metastases (18 %), elevated baseline lactate dehydrogenase (19 %) and poor performance status (15 %), and elderly patients (22 %). Median PFS was 5.8 (95 % CI 5.0–6.4) months; median OS was 10.5 (95 % CI 9.5–13.5) months.
Conclusion
Our results for Spanish patients in the vemurafenib safety study indicate similar efficacy and a comparable safety profile in Spanish patients with no new safety signals compared with the overall population. Clinical benefit was demonstrated in poor-prognosis patients and in those with favourable baseline characteristics, suggesting that poor-prognosis patients may also benefit from vemurafenib treatment.
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Acknowledgments
The authors would like to thank the patients and their families, as well as the Spanish investigators and their associates, for their participation in the vemurafenib safety study. Support for third-party writing assistance for this manuscript was provided by Roche Farma, Spain. The global vemurafenib safety study was supported by F. Hoffmann-La Roche and the Spanish sub-analysis was sponsored by Roche Farma, Spain.
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Enrique Espinosa has participated in advisory boards for Roche Farma. Ana Arance has participated in advisory boards for Roche Farma and has given presentations on behalf of Roche Farma. Salvador Martín Algarra has participated in advisory boards for Roche Farma. Jose Lopez-Martin has participated in advisory boards for Roche Farma. Alfonso Berrocal has participated in advisory boards for Roche Farma and has given presentations on behalf of Roche Farma. Beatriz La Orden is an employee of Roche Pharma Spain. Luis de la Cruz-Merino, Pablo Cerezuela, Virtudes Soriano and Lorenzo Alonso have no conflicts to declare.
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Arance, A.M., Berrocal, A., Lopez-Martin, J.A. et al. Safety of vemurafenib in patients with BRAF V600 mutated metastatic melanoma: the Spanish experience. Clin Transl Oncol 18, 1147–1157 (2016). https://doi.org/10.1007/s12094-016-1498-9
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DOI: https://doi.org/10.1007/s12094-016-1498-9