Melanoma

The risk of death was significantly reduced for patients with BRAFV600E/K mutation-positive metastatic melanoma treated with dabrafenib and trametinib compared with dabrafenib alone.

Epigenetic and genetic biomarkers are potential methods of early detection of melanoma and other types of skin cancer. Earlier diagnosis alone would improve survival, even in the absence of novel therapies.

Metastatic disease accounts for the vast majority of cancer-related deaths. Ensuring a definitive diagnosis and the most effective treatment in a timely fashion is essential for extending life expectancy.

Reported results from the coBRIM study have shown that combining the BRAF inhibitor vemurafenib with cobimetinib, a MEK inhibitor, increases progression-free survival (PFS) in patients with BRAF-mutated advanced melanoma compared with vemurafenib alone.

Researchers are finding new ways to diagnose melanoma using machine learning methods.

Cytavis Biopharma GmbH, a Germany-based pharmaceutical company, is developing a natural protein, aviscumine (CY-503), as an immunostimulatory agent to improve response to immunotherapeutic treatment of melanoma.

The FDA approved nivolumab for patients with advanced melanoma in December 2014, joining 6 other melanoma treatments approved in the past 3 years, including monoclonal antibodies pembrolizumab and ipilimumab.

The FDA has approved nivolumab (Opdivo) for patients with unresectable or metastatic melanoma following treatment with ipilimumab or a BRAF inhibitor, based on data from the phase III CheckMate-037 trial.

The programmed death receptor-1 (PD-1) ligand, PD-L1, has become a viable target for immunotherapy in cancer, with multiple antibodies now in development.

Checkpoint inhibition has demonstrated efficacy for the treatment of melanoma in several clinical trials. However, biomarkers to predict safety and efficacy of immunotherapies in individual melanoma patients are lacking.

Scientists are beginning to find that combination therapy improves outcomes for patients, particularly with ipilimumab-nivolumab combination therapy.

Knowledge of genetic expression of melanocytic lesions significantly reduced the number of indeterminate diagnoses made by dermatopathologists.

Pembrolizumab (Keytruda) significantly improved progression-free survival (PFS) by over 43% compared with chemotherapy as a treatment for patients with metastatic melanoma who were refractory to ipilimumab (Yervoy).

Frontline treatment with nivolumab (Opdivo) significantly extended overall survival (OS) and progression-free survival (PFS) when compared with dacarbazine in patients with untreated BRAF wild-type advanced melanoma.

Several novel approaches to the delivery of therapeutics for advanced melanoma may improve treatment efficacy and patient survival.

Adding the GM-CSF agent sargramostim to the CTLA-4 inhibitor ipilimumab (Yervoy) prolonged overall survival (OS) and lowered toxicity for patients with unresectable stage III or IV melanoma.

The FDA has expanded the approval of Lymphoseek (technetium Tc 99m tilmanocept) injection to include sentinel lymph node (SLN) detection for breast cancer and melanoma as well as lymphatic mapping in solid tumors.

Nanotechnology is unlikely to enter the arena of melanoma therapy, overshadowed as it is by the promising developments in combination treatment with immune checkpoint inhibitors, tumor-infiltrating lymphocyte therapies, and other immunotherapies.

Harriet Kluger, MD, associate professor of medicine, Yale Cancer Center, discusses the toxicity profile of concurrent nivolumab and ipilimumab as seen in a phase I trial.

Patients with unresectable melanoma had a significant improvement in the odds of survival when treated in first line with a combination of BRAF and MEK inhibitors, as opposed to anti-BRAF monotherapy.

Treatment with nivolumab (Opdivo) demonstrated superior objective response rates (ORR) and longer durations of response compared with chemotherapy in a phase III trial of patients with previously treated advanced metastatic melanoma

The FDA has assigned a priority review designation to nivolumab for pretreated patients with advanced melanoma, setting an action date for the drug as March 30, 2015.

Lawrence Fong, MD, discusses the systemic antitumor effect and clinical response in a phase II trial of intratumoral electroporation of plasmid interleukin-12 (IL-12) in patients with advanced melanoma.

Of the many signaling cascades being targeted for therapeutic intervention in cancer, one of the most important and best understood is the MAPK pathway, particularly the RAS/RAF/MEK/ERK cascade.

Igor Puzanov, MD, medical oncologist, Vanderbilt-Ingram Cancer Center, discusses the potential to partner T-VEC with a targeted agent for the treatment of patients with melanoma.