Safety of vemurafenib in patients with BRAF V600 mutated metastatic melanoma: the Spanish experience

• A. M. Arance ^[6] ; A. Berrocal ^[1] ; J. A. Lopez-Martin ^[2] ; L. de la Cruz-Merino ^[7] ; V. Soriano ^[3] ; S. Martín Algarra ^[4] ; L. Alonso ^[8] ; P. Cerezuela ^[9] ; B. La Orden ^[10] ; E. Espinosa ^[5]
  1. [1] Hospital General Universitario de Valencia

     Hospital General Universitario de Valencia

     Valencia, España

     
  2. [2] Hospital Universitario 12 de Octubre

     Hospital Universitario 12 de Octubre

     Madrid, España

     
  3. [3] Instituto Valenciano de Oncologia

     Instituto Valenciano de Oncologia

     Valencia, España

     
  4. [4] Clínica Universitaria de Navarra

     Clínica Universitaria de Navarra

     Pamplona, España

     
  5. [5] Hospital Universitario La Paz

     Hospital Universitario La Paz

     Madrid, España

     
  6. [6] Hospital Clínic, Barcelona, España
  7. [7] Hospital Universitario Virgen de la Macarena, España
  8. [8] Hospital Clínico de Málaga, España
  9. [9] Hospital Universitario Santa Lucía de Cartagena, España
  10. [10] Roche Farma, Madrid, España

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 18, Nº. 11 (November 2016), 2016, págs. 1147-1157
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Objectives Vemurafenib tolerability was assessed in a large, open-label, multicentre study in patients with BRAFV600 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, BRAFV600 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.