Melanoma Breakthroughs Among Top 2011 Cancer Advances

Oncology & Biotech News, January 2012, Volume 6, Issue 1

Two novel treatments for advanced melanoma, ipilimumab (Yervoy) and vemurafenib (Zelboraf), were among the top breakthroughs in cancer research in 2011.

Two novel treatments for advanced melanoma, ipilimumab (Yervoy) and vemurafenib (Zelboraf), were among the top breakthroughs in cancer research in 2011, according to ASCO’s annual review Clinical Cancer Advances 2011: ASCO’s Annual Report on Progress Against Cancer. The 2 therapies have been hailed as the first new drugs for the treatment of advanced melanoma in over 30 years.

The advances are considered critical because they help patients with a poor prognostic outlook. “Late-stage melanoma is devastating, with very few treatment options for patients, none of which previously prolonged a patient’s life,” according to Richard Pazdur, MD, director of the FDA’s Office of Hematology and Oncology Products.


In March 2011, the FDA approved the immunotherapy ipilimumab to treat patients with late-stage melanoma. The drug is a monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), which researchers suggest may play a role in disarming the body’s immune system, affecting its ability to fight malignancies. It is suspected that ipilimumab’s anti—CTLA-4 activity allows the immune system to recognize, target, and attack cells in melanoma tumors.

The FDA approved ipilimumab based on a phase III study of 676 patients with unresectable late-stage melanoma who had stopped responding to standard treatment. The study randomized patients to ipilimumab plus an experimental tumor vaccine called gp100, ipilimumab alone, or gp100 alone.

The median overall survival was approximately 10 months for patients in the 2 ipilimumab arms versus 6.5 months in patients receiving gp100 alone. Along with this significant benefit, ipilimumab’s immunotherapeutic mechanism of action is also associated with potentially severe and fatal immune-mediated adverse reactions. Consequently, the FDA approved ipilimumab with a Risk Evaluation and Mitigation Strategy to facilitate successful treatment.


In August 2011, the FDA approved vemurafenib, which inhibits a common mutation in melanoma called BRAF V600E. The BRAF protein is involved in regulating cell growth and is mutated in about 50% of patients with late-stage melanomas. The FDA’s approval of the treatment was based on a phase III study of 675 previously untreated patients with late-stage melanoma with the BRAF V600E mutation. Patients were randomized to either vemurafenib or standard treatment with dacarbazine.

At 6 months’ follow-up, the overall survival rate in the vemurafenib arm was 84%, versus 64% in the dacarbazine arm. Tumor shrinkage occurred in 48% of patients receiving vemurafenib, as compared with 5% of patients receiving dacarbazine. Additionally, vemurafenib lowered the risk of disease progression by 74% versus standard chemotherapy.

According to the FDA, the most common toxicities reported in the vemurafenib group were joint pain, rash, hair loss, fatigue, nausea, and skin sensitivity when exposed to the sun. Approximately 1 in 4 patients receiving vemurafenib developed nonmelanoma skin cancers that could be managed through surgery.

Wolfram E. Samlowski, MD, of the Comprehensive Cancer Centers of Nevada and a specialty editor of the ASCO report, discussed the use of vemurafenib versus ipilimumab. “In patients with rapidly growing or large tumor burden BRAF V600E disease, vemurafenib is the drug of choice, because the onset of action of ipilimumab is too slow. In patients with small amounts of tumor or limited sites of metastases, the order of treatment may not be critical.” Samlowski also noted that manufacturers Bristol-Myers Squibb (ipilimumab) and Genentech (vemurafenib) are researching the possibility that the 2 drugs could be used together.

Samlowski is also hopeful that the discovery of ipilimumab and vemurafenib might spur more research in targeted therapies for melanoma. “It is fascinating to me that when new agents are developed, that there is a rush to ‘me-too’ agents. A number of companies have other BRAF inhibitors in development. In addition, the scientific knowledge that is gained also leads to the understanding of novel pathways involved in cancer growth or resistance to existing treatments. This [can lead] to a surprising number of new and active drugs, as well as combination therapies being discovered. This process is currently under way in melanoma.”

Other Strides Made

Beyond the melanoma breakthroughs in 2011, significant progress was made in several other areas of cancer care. Here are some of the other key advances included in the ASCO 2011 report:

  • The approval of crizotinib (Xalkori) for patients with advanced non—small cell lung cancer who harbor an alteration in the anaplastic lymphoma kinase (ALK) gene.
  • Conclusive evidence that an aromatase inhibitor, exemestane (Aromasin), reduced the risk of developing a first breast cancer in high-risk postmenopausal women, making the drug a preventive treatment option in this population.
  • A large national screening trial of more than 50,000 current and former heavy smokers that found 3 annual low-dose computed tomography scans reduced death rates from lung cancer by 20%.

Vogelzang NJ, Benowitz SI, Adams S, et al. Clinical Cancer Advances 2011: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology [published online ahead of print December 5, 2011]. J Clin Oncol. doi:10.1200/JCO.2011.40.1919.