Melanoma

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.

Several advances in the treatment of metastatic melanoma have occurred in the last 5 years, one of which has been the approval by the FDA of targeted treatments for patients with melanomas harboring a BRAF mutation.

Mario Sznol, MD, professor, Internal Medicine, Yale Cancer Center, discusses the potential for immunotherapy combinations for the treatment of melanoma.

Unlike many other types of tumors, melanoma can be detected early in its progression by visual, noninvasive methods.

Only in the last 2 decades or so have sufficient data become available to statistically associate high mitotic rate with survival in melanomas.