Giving melanoma patients a break from vemurafenib could make this treatment more effective. Research in Nature shows that vemurafenib-resistant tumors keep growing during treatment because they produce high levels of mutated BRAF proteins, which are involved in cell division. Moreover, these tumors actually depend on the drug to grow. In contrast, an on-and-off treatment schedule can help keep melanomas from becoming resistant to vemurafenib in mice.
Based on current data, researchers have developed a new treatment guide for melanomas with the most common mutations (BRAF V600). While these melanomas can be targeted with vemurafenib and dabrafenib, challenges remain. Not all tumors respond, some become resistant, and side effects can include another type of skin cancer called squamous cell carcinoma. Other treatment options include trametinib, which targets a protein called MEK, as well as immunotherapies such as high-dose interleukin 2 and ipilimumab, both of which can control tumors completely.
A JAMA Surgery study clarified when melanoma is likely to return in people determined to be cancer-free by sentinel lymph node biopsy. The researchers found that melanoma recurred in 16% of 515 such patients and that 4% of them had tumors in the lymph nodes that had been tested. Recurrence was more likely when the initial tumors were on the head or neck and were deeper (2.7 vs. 1.8 mm). Recurrence was less likely in women and in people who were younger when first diagnosed.
A JAMA Dermatology study shows the dangers of using smartphone apps to self-diagnose melanomas. The researchers compared diagnoses of 60 melanomas and 128 benign lesions by a board-certified dermatopathologist to those of four apps. Three of the apps incorrectly said that 30% or more of the melanomas were harmless. The fourth app, which sent images to board-certified dermatologists, was better, but still misdiagnosed one of the melanomas as benign. These apps are not subject to regulatory oversight.
Pharmaceutical firm GlaxoSmithKline has started a phase III study to see if a drug combination can prevent or delay the recurrence of melanomas with BRAF V600 mutations. Both drugs—dabrafenib, a BRAF inhibitor and trametinib, a MEK inhibitor—are experimental; the study will assess the efficacy and safety of the combination. The researchers plan to enroll about 850 people from more than 200 sites worldwide in the study. Another pharmaceutical firm, Roche, is also doing late-stage trials of a different BRAF inhibitor/MEK inhibitor combination.
Biotech company Genentech has added a MEK inhibitor to a phase III trial of vemurafenib, an FDA-approved BRAF inhibitor. MEK inhibitors have been shown to counteract resistance to BRAF inhibitors. The experimental MEK inhibitor is called GDC-0973, and is also known as XL-518 or RG7421. Vemurafenib (Zelboraf®) targets melanomas with BRAF V600 mutations, which are found in about half of these aggressive skin cancers. Genentech is part of the Roche Group; the two companies are conducting this combination treatment trial jointly.
New research in Nature shows that the immune system can control tumors permanently without destroying cells. The researchers treated cancers with two proteins that activate the immune system (interferon-g and tumor necrosis factor) and found that the combination kept tumors from growing by making the cells dormant. This work could ultimately lead to cancer treatments that are both effective and free of side effects, suggesting that we shift from the “war on cancer” strategy of killing tumor cells to focus instead on restoring the body’s innate ability to arrest tumor development.
Where there were no treatment options for metastatic melanoma patients in the past, there are now several. Prior to 2010, only two treatments were approved: the chemotherapy drug dacarbazine and recombinant human interleukin 2 (IL-2) immunotherapy. Neither was effective in providing durable responses or led to an improvement in overall survival.
But now, the immunotherapy antibody ipilimumab and the targeted oral therapy vemurafenib, a BRAF inhibitor, have been shown to improve overall survival. Both were approved by the Food and Drug Administration (FDA) in 2011. Continue reading…