Melanoma

Pooled analysis, presented at the 2016 ASCO Annual Meeting, showed the safety profile of dabrafenib and trametinib is consistent with reports from three individual studies.

Treatment with dabrafenib (Tafinlar) plus trametinib (Mekinist) resulted in a complete response in 9 of 19 patients with stage IIIb/c BRAF V600 melanoma, according to results from a phase II trial presented at the 2016 ASCO Annual Meeting.

Three years after the pembrolizumab (Keytruda) clinical trial for advanced melanoma that led to the drug's FDA approval, 40% of the patients are still alive.

With expanding availability of effective single-agent and combination immunotherapies and combination BRAF/MEK inhibitor regimens, all of which have been shown to improve survival and reduce risk of progression, the optimal sequencing of therapies has become increasingly complex.

A number of new combination approaches have gained approval in the past year for the treatment of patients with BRAF-mutant metastatic melanoma, expanding the number of effective treatment options that can improve quality and length of life for many patients.

With the development of novel targeted and immunotherapeutic agents that are more efficacious than traditional chemotherapy, treatment paradigms in melanoma have undergone major changes.

BRAF mutation testing has become an essential tool in the diagnostic workup and management of patients with advanced melanoma.

Hedgehog inhibitors have revolutionized the treatment paradigm for patients with advanced basal cell carcinoma, says Desiree Ratner, MD.

Toni Ribas, MD, discusses the significance of the CheckMate-069 data and where the field of immunotherapy in melanoma is headed.

By working together, the potential for clinical benefit in patients with cancer is increasingly bright.

Single-agent nivolumab (Opdivo) demonstrated a robust 5-year overall survival (OS) rate of 34% for heavily pretreated patients with metastatic melanoma who had not received prior ipilimumab (Yervoy), according to long-term findings from a single-arm phase I study.

Immunotherapy should be considered along with VEGF and mTOR TKIs as a highly effective treatment modality for patients with metastatic renal cell carcinoma (RCC).

PD-1/PD-L1 should be the backbone of melanoma treatment for many patients, says Jason Luke, MD, an assistant professor of Medicine at the University of Chicago Medicine.

Postow cites the combination of vemurafenib and ipilimumab as one that produced a high rate of liver inflammation and skin rash in patients, which was then deemed not to be given to patients outside of clinical trials.

Atkins says because treatments currently used in patients with visible metastatic melanoma are normally efficacious between 50% and 60% of the time, then the expectation for these treatments in the adjuvant setting could be effective around 80% of the time.

Gangadhar says this preference toward single-agent immunotherapy is due to a lack of evidence supporting the use of a combination immunotherapy approach. The other reason a dual approach is less utilized in melanoma patients is due to the significant increase in toxicities.

Instead of adjuvant treatment, Andtbacka suggests treating patients with melanoma in the neoadjuvant setting. The benefit of neoadjuvant treatment versus adjuvant treatment is that oncologists can see the effect on the tumor, as well as perform biopsies and be able to determine changes in the tumor to develop certain biomarkers.

Weber says these treatments, such as ipilimumab plus nivolumab, or dabrafenib and trametinib, have seen marked improvements since 2009, and continue to become more important in the treatment paradigm of melanoma.

Fischkoff says the goal of Lion Biotechnologies is to utilize a central manufacturing facility where medical professionals can submit tumor samples of their patients, and received the proper TIL-based treatment back from the manufacturing facility.

A recent publication from The Cancer Genome Atlas (TCGA) has opened the door wide for a slew of new, non-BRAF targeted agents in melanoma, according to Jason J. Luke, MD, FACP.

With the proven efficacy of both BREF/MEK inhibitors and immunotherapies, Jeffrey S. Weber, MD, PhD, discusses which to use first in patients with melanoma.

Hamid says the future will hold adding more tolerable regimens in to the treatment paradigm of melanoma, based on the past success of the treatments already utilized and approved.

Postow says there have been algorithms developed over recently years to determine patient's toxicities and prescribe certain immunosupressive treatments to help abate the symptoms.

The purpose of this article is to discuss the efficacy, indications for use, and safety of oral Hh pathway inhibitors for locally advanced BCC (LABCC) and for metastatic BCC (MBCC) through a review of the literature.

With a growing armamentarium for treating metastatic BRAF-mutated melanoma, choosing the right regimen can be difficult, says Jeffrey S. Weber, MD, PhD.

Sharpe, whose lab aided in the discover of the pathway, says blocking the pathway in order to treat cancers is important because it allows T cells to work better.

Yardena Samuels, PhD, on the ineffectiveness of targeting a single gene of proteins in patients with melanoma. Samuels says this strategy may work for the short term for treatment, but patients would tend to develop a resistance much quicker to treatment strategies using this method.

Despite limited information on treatment options for mucosal melanoma, Richard Joseph, MD, says immunotherapies could be a rewarding challenge for oncologists to undertake in the field.

Holmen says that utilizing targeted therapies could potentially be the answer, though clinically-tested combinations have historically not done as well as clinicians had hoped.

Weber says overactivity of these EGFR receptors may cause SCC tumors to become more aggressive. He adds that in a recent, small-scale study, effectively blocking the EGFR receptor in the tumor with anti-EGFR therapy proved to be successful.