What’s the News: Three new drugs have been shown to improve survival and slow disease progress in patients with metastatic melanoma. This advanced form of the disease is the deadliest type of skin cancer, with patients surviving for an average of only 6 to 9 months. Phase III clinical trials of the treatments—a new chemotherapy drug, an immune-system treatment combined with traditional chemotherapy, and a vaccine combined with another immune treatment—were recently published in the New England Journal of Medicine.
New Chemotherapy Drug:
- The chemotherapy drug, vemurafenib, blocks some of the effects of BRAF gene mutations, which are found in about 60% of melanomas.
- In this study, the researchers compared how 675 advanced melanoma patients with mutated version of the BRAF gene fared when taking either vemurafenib or dacarbazine, a chemotherapy drug often used to treat the disease.
- Tumors shrank significantly in 48% of patients on vemurafenib, but in only 5% of patients given dacarbazine. The new drug also improved the six-month survival rate to 84%, compared to 64%.
- These results were so encouraging that the researchers stopped the study partway through, to switch patients who had been taking dacarbazine to the new drug.
- Not So Fast: Vemurafenib shrinks tumors for only a short time. The tumors are able to switch on pathways that essentially let them become resistant to the drug, and tend to come back within a year. While the drug improves six-month survival rates, it’s not clear whether it improves overall survival, the average length of time patients live after their diagnosis.
Immune System Treatment Plus Chemo:
- The immune-system treatment, ipilimumab—recently approved by the FDA under the brand name Yervoy—is a biologically engineered drug that boosts the immune system’s ability to battle cancer cells.
- The researchers gave 502 patients with metastatic melanoma either ipilimumab and dacarbazine, the chemotherapy drug, or dacarbazine and a placebo.
- After three years, 21% of patients receiving ipilimumab in addition to chemotherapy were still alive, compared to 12% of patients taking only dacarbazine.
- The addition of ipilimumab to traditional chemo boosted median survival by 2 months, from 9 months to 11 months.
- Not So Fast: An extra two months, on average, isn’t very much. The drug dramatically increased the survival of a small group of patients, but there isn’t a clear way to tell why certain patients responded so well.
Vaccine Plus Immune Treatment:
- In a third clinical trial, researchers combined a melanoma vaccine with interleukin-2, a drug that bolsters the body’s immune response. Unlike preventative vaccines, which are meant to keep people from getting sick, this vaccine revs up the immune system to attack cancer cells.
- The researchers gave 185 patients with advanced melanoma one of two treatments: the vaccine and interleukin-2, or interleukin-2 alone.
- Tumors shrank by at least half in 16% of patients who got the vaccine and interleukin-2, compared to 6% of those who only got the drug.
- The vaccine/drug combo also increased average survival by 7 months over the drug alone, from 11 months to 18 months.
- Not So Fast: The results weren’t quite strong enough to be statistically significant, meaning more trials must be done to see if the vaccine really does help. In addition, the vaccine increased the incidence of some serious side effects, including temporary heart problems.
The Future Holds:
- While each of these treatments has shortcomings, “the future is going to be to build upon the success” of each by testing them in combination, Dr. Allen Lichter, CEO of the American Society of Clinical Oncology, told the Associated Press.
- Bristol-Myers Squibb, which makes ipilimumab, and Roche, which makes vemurafenib, are doing just that, teaming up to test whether the two drugs are safe and effective when administered together.
- Paul B. Chapman et al. “Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation.” New England Journal of Medicine, published online June 5, 2011. DOI:10.1056/NEJMoa1103782
- Caroline Robert et al. “Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma.” New England Journal of Medicine, published online June 5, 2011. DOI:10.1056/NEJMoa1104621
- Douglas J. Schwartzentruber et al. “gp100 Peptide Vaccine and Interleukin-2 in Patients with Advanced Melanoma.” New England Journal of Medicine, June 2, 2011.