Sosman and colleagues evaluated the overall response rate, duration of response, and overall survival of vemurafenib in previously treated patients with BRAF V600 mutant-metastatic melanoma.22 In this multicenter, Phase 2 trial, 132 patients received vemurafenib 960mg orally twice daily until the development of unacceptable adverse effects or disease progression. Patients with disease progression could continue with vemurafenib if it was thought that the patient would benefit clinically. Median follow-up was 12.9 months with a range of 0.6 to 20.1 months. The confirmed overall response rate was 53%, with 6% experiencing a complete response, and 47% experiencing a partial response. The median duration of response was 6.7 months and median progression-free survival was 6.8 months. Primary disease progression was only observed in 14% of treated patients. Response was not necessarily observed right away. Some patients did not start to experience a response until 6 months after treatment started. The median overall survival was 15.9 months. Vemurafenib appeared to be well tolerated. The more commonly reported adverse effects included grade 1 or 2 arthralgia, rash, photosensitivity, fatigue, and alopecia. This clinical trial was able to demonstrate that vemurafenib can induce clinical responses in previously treated patients with BRAF V600 mutant-metastatic melanoma over an extended period of time (16 months).

The search for safe and effective advanced melanoma cancer treatment therapies has been a long and difficult struggle. The introduction of ipilimumab and vemurafenib may be the beginning of the identification of melanoma treatment options that improve survival outcomes based upon patient immune response.

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1. American Cancer Society. Melanoma skin cancer. Learn About Cancer website. Accessed April 2, 2012.

2. National Cancer Institute. SEER stat fact sheets: melanoma of the skin. Surveillance Epidemiology and End Results (SEER) website. Accessed April 4, 2012

3. Jemal A, Siegel R, Xu J., Ward E. Cancer statistics, 2010 [published correction appears in CA Cancer J Clin. 2011;61(2):133-134]. CA Cancer J Clin. 2010;60(5):277–300.

4. Bleyer A, Barr R. Cancer in young adults 20 to 39 years of age: overview. Semin Oncol. 2009;36(3):194–206.

5. Reed K.B., Brewer J.D., Lohse C.M., et al. Increasing incidence of melanoma among young adults: an epidemiological study in Olmsted County, Minnesota. Mayo Clin Proc. 2012;87(4):328–334.

6. Melero I., Hervas-Stubbs S., Glennie M., et al. Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer. 2007;7(2):95–106.

7. O’Day S.J., Hamid O., Urba W.J., Targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4): a novel strategy for the treatment of melanoma and other malignancies. Cancer. 2007;110(12):2614–2627.

8. Fong L., Small E.J., Anti-cytotoxic T-lymphocyte antigen-4 antibody: the first in an emerging class of immunomodulatory antibodies for cancer treatment. J Clin Oncol. 2008;26(32):5275–5283.

9. Robert C., Ghiringhelli F. What is the role of cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma? Oncologist. 2009;14(8):848-861.

10. Weber J., Thompson J.A., Hamid O., et al. A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma. Clin Cancer Res. 2009;15(17):5591–5598.

11. Wolchok J.D., Neyns B., Linette G., et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol. 2010;11(2):155–164.

12. O’Day S.J., Maio M., Chiarion-Sileni V., et al. Efficacy and safety of ipilimumab monotherapy in patients with pretreated, advanced melanoma: a multicenter, single-arm phase II study. Ann Oncol. 2010;21(8):1712–1717.

    13. Agarwala S.S. Novel immunotherapies as potential therapeutic partners for traditional or targeted agents: cytotoxic T-lymphocyte antigen-4 blockade in advanced melanoma. Melanoma Res. 2010;20(1):1–10.

    14. Downey S.G., Klapper J.A., Smith F.O., et al. Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Clin Cancer Res. 2007;13(22 Pt 1):6681–6688.

    15. Hodi F.S., McDermott D.F., Weber R.W., et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Eng J Med. 2010;363(8):711–723.

    16. Robert C., Thomas L., Bondarenko I., et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–2526.

    17. Postow M.A., Callahan M.K., Barker C.A., et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012;366(10):925–931.

    18. Drake C. Radiation-induced immune modulation. In: DeWeese TL, Laiho M, eds. Molecular Determinants of Radiation Response. New York, NY: Springer; 2011:251–263.

    19. Yuan J., Adamow M., Ginsberg B.A., et al. Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab. Proc Natl Acad Sci U S A. 2011;108(40):16723–16728.

    20. Davies H, Bignell G.R., Cox C., et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–954.

    21. Gray-Schopfer V., Wellbrock C., Marais R., Melanoma biology and new targeted therapy. Nature. 2007;445(7130):851–857.

    22. Sosman J.A., Kim K.B., Schuchter L., et al., Survival in BRAF V600–mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012;366(8):707–714.