Posted on November 14th, 2014 by
By one estimate, over the past three decades more people in the United States have had skin cancer than all other cancers combined.1 According to the American Cancer Society, 3.5 million cases of basal and squamous cell skin cancer are diagnosed each year.2 Rates of melanoma—the deadliest form of skin cancer—are on the rise,2 particularly among people younger than 40, increasing fourfold among men and eightfold among women in this age group since 1970.3
Most skin cancers, including melanoma, are highly curable with surgery if detected and treated early. For patients in whom skin cancer has progressed, however, treatment options have been limited. Several new drugs—the first generation of “targeted therapies” for advanced skin cancer—are starting to change that.
Unlike conventional chemotherapy drugs that attack both normal and cancerous cells, targeted therapies are designed to block specific substances or pathways in cancer cells that enable tumors to grow.
“Think of a light switch that’s stuck in the on position,” explains Darrell Rigel, MD, clinical professor of dermatology at New York University Langone Medical Center and a spokesman for the Skin Cancer Foundation. “As long as the switch is on, the cancer keeps growing. What these new drugs do is cut the wire or turn the switch off.”
Although none of these new drugs is a cure, Dr. Rigel emphasizes, “they are much, much better than anything we have had before to treat advanced skin cancer.”
Since 2011 the US Food and Drug Administration (FDA) has approved five new drugs to treat advanced melanoma.
As promising as all of these new drugs are, says Dr. Rigel, they often stop working within six months to a year as melanoma cells find another pathway that lets them start growing again. Researchers are now testing combinations of two or more of these new drugs, which they believe may produce better results than any one drug by itself. For example, in patients treated with a high dose of Mekinist plus Tafinlar, tumors stopped growing for more than nine months on average, compared with just under six months for patients who took Tafinlar alone. Nearly eight in 10 patients who received the combined regimen were still alive after one year.10
A drug called talimogene laherparepvec (TVEC) that is not yet FDA approved is showing promise in clinical studies. Patients treated with TVEC survived for nearly two years on average, compared with 19 months for patients who received an immune-system-stimulating drug.11 TVEC is a virus modified to grow inside tumor cells.
Advanced Basal Cell Cancer
Advanced basal cell cancer is a rare disease for which there was no effective treatment until the approval of Erivedge® (vismodegib) in 2012. The drug blocks cellular signals that tell the cancer cells to grow. Tumors stopped growing for 9.5 months on average.12 After a further two years of follow-up, patients with metastatic basal cell cancer (tumors had spread to other organs) had lived for just under three years on average.13
A few patients have been taking the drug for as long as five years, says Aleksandar Sekulic, MD, PhD, assistant professor of dermatology at the Mayo Clinic in Scottsdale, Arizona, who led the trial that resulted in the approval of Erivedge. The most common side effects of treatment have included hair loss, muscle cramps, and the loss of taste sensation.
1. Stern, RS. Prevalence of a history of skin cancer in 2007: results of an incidence-based model. Archives of Dermatology. 2010;146(3):279-82. doi: 10.1001/archdermatol.2010.4.
2. Cancer Facts & Figures 2013. American Cancer Society website. Available at: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-036845.pdf. Accessed January 17, 2014.
3. Reed KB, Brewer JD, Lohse CM, Bringe KE, Pruitt CN, Gibson LE. Increasing incidence of melanoma among young adults: an epidemiological study in Olmsted County, Minnesota. Mayo Clinic Proceedings. 2012;87(4):328-34. doi: 10.1016/j.mayocp.2012.01.010.
4. Ribas A, Hodi FS, Kefford R, et al. Efficacy and safety of the anti-PD-1 monoclonal antibody MK-3475 in 411 patients (pts) with melanoma (MEL). J Clin Oncol 32:5s, 2014.
5. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. New England Journal of Medicine. 2011;364(26):2517-26. doi: 10.1056/NEJMoa1104621.
6. Schadendorf D, Hodi FS, Robert C, et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in metastatic or locally advanced, unresectable melanoma. Paper presented at: 38th Congress of the European Society for Medical Oncology; September 27–October 1, 2013; Amsterdam, Netherlands. Abstract LBA24.
7. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. New England Journal of Medicine. 2011;364(26):2507-16. doi: 10.1056/NEJMoa1103782.
8. Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358-65. doi: 10.1016/S0140-6736(12)60868-X.
9. Flaherty KT, Robert C, Hersey P, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. New England Journal of Medicine. 2012;367(2):107-14. doi: 10.1056/NEJMoa1203421.
10. Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. New England Journal of Medicine.2012;367(18):1694-703. doi: 10.1056/NEJMoa1210093.
11. Amgen Presents Interim Overall Survival Data from Phase 3 Study of Talimogene Laherparepvec in Patients with Metastatic Melanoma [news release]. November 18, 2013. Available at http://www.prnewswire.com/news-releases/amgen-presents-interim-overall-survival-data-from-phase-3-study-of-talimogene-laherparepvec-in-patients-with-metastatic-melanoma-232394381.html. Accessed January 17, 2014.
12. Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. New England Journal of Medicine. 2012;366(23):2171-79. doi: 10.1056/NEJMoa1113713.
13. Sekulic A, Migden MR, Oro AE, et al. Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma (aBCC): 24-month update of the pivotal ERIVANCE BCC study. Paper presented at: European Academy of Dermatology and Venereology; October 3, 2013; Istanbul, Turkey. Abstract FCO2.7.
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