Targeted Therapy Combinations Still Key in Metastatic Melanoma

“Combinations of targeted therapies continue to advance toward full regulatory approval for patients with metastatic or unresected melanoma, given the substantial benefits seen with these agents. At this time, the FDA is considering two applications for separate combinations of BRAF and MEK inhibiting agents for patients with unresectable or metastatic BRAFV600 mutation-positive melanoma.

“ ‘The future of the treatment of melanoma is clearly going to be in combinations, both for targeted therapy and for immunotherapy,’ said Jeffrey S. Weber, MD, PhD, who recently joined the NYU Langone Medical Center. ‘Already, there is an FDA-approved combination therapy that is targeted; that is dabrafenib and trametinib. There are new combinations coming up, mainly concerning CDK 4/6 and MEK inhibitors in NRAS-mutated but BRAF wild-type melanoma, which is an unmet medical need.’ “

What Determines Whether a Melanoma Patient Will Respond to Checkpoint Blockade Drugs?

Of all cancer types, melanoma is the most investigated in terms of its potential to be treated through immune system-based approaches. More immunotherapy drugs are approved for melanoma than for any other type of cancer, and more are in development. Recent additions to the immunotherapy arsenal are the ‘anti-PD-1’ immune checkpoint blockade drugs pembrolizumab (Keytruda) and nivolumab (Opdivo). Continue reading…

Immune Checkpoint Inhibitors in Melanoma: New Directions

The drugs pembrolizumab (Keytruda) and nivolumab (Opdivo) were approved by the U.S. Food and Drug Administration (FDA) in 2014 and 2015, respectively. These two competing blockbuster drugs are already changing the outlook in metastatic melanoma, previously considered to be a fatal disease. Known as ‘immune checkpoint inhibitors,’ they work by releasing ‘brakes’ on a patient’s own immune system, freeing it to attack tumors. In the wake of their success, researchers are now taking immune checkpoint inhibition in new directions. Continue reading…

NRAS & BRAF Mutational Status May Help Guide Therapy in Melanoma Patients

“A new study is suggesting that it may be important to look at mutational status when determining adjuvant treatments for melanoma patients. Researchers at the University of North Carolina (UNC) School of Medicine are now reporting that NRAS and BRAF mutations in melanoma patients should be identified early, and may need to be taken into consideration when establishing treatment paradigms.

“The results of this study were published online in the April 9, 2015 issue of JAMA Oncology.

“Researchers looked at data from the Genes, Environment, and Melanoma (GEM) Study, which included 912 patients with a median follow-up of 7.6 years. They examined tumor characteristics and melanoma-specific survival of primary melanoma by NRAS and BRAF mutational status.  They found 13% of the patients had tumors with NRAS mutations, 30% had BRAF mutations, and 57% had neither.

“There was no statistically significant difference in the 5-year survival rates for patients with NRAS or BRAF-mutated melanoma tumors compared with survival in those patients with tumors lacking mutations. However, there were lower 5-year survival rates for patients with higher-risk tumors with mutations. The study suggested the 5-year survival rate was 73% for patients with high-risk NRAS-mutated tumors, 71% for patients with high-risk tumors with BRAF mutations, and 82% for patients with high-risk cancer and lacking either mutation.”

Melanomas with NRAS Mutations Are More Responsive to Immunotherapies

“Researchers investigating whether tumor genotype correlates with benefit from immune therapy in melanoma has found that patients whose tumors had NRAS mutations had better response to immunotherapy and better outcomes than patients whose tumors had other genetic subtypes. The results suggest that immune therapies, especially immune checkpoint inhibitors, may be particularly effective treatment options for NRAS-mutant melanoma. Activating NRAS mutations are found in 15% to 20% of melanomas. The study by Johnson et al is published in Cancer Immunology Research.

“Between 2010 and 2012, the researchers reviewed the electronic medical records of 229 patients with melanoma treated at Vanderbilt-Ingram Cancer Center in Nashville, Memorial Sloan Kettering Cancer Center in New York, and Massachusetts General Hospital in Boston. Of these patients, 143 received ipilimumab (Yervoy), 58 received interleukin (IL)-2 (Proleukin), and 28 received anti–PD-1 (nivolumab [Opdivo] or pembrolizumab [Keytruda]) or anti–PD-L1 (MPDL3280A) therapy.

“All patients underwent genotyping for ‘hotspot’ mutations in BRAF and NRAS; most patients also underwent ‘hotspot’ testing of other genes, including CKIT, GNAQ, GNA11, and MEK1. Sixty patients (26%) had tumors with NRAS mutations, 53 (23%) had BRAF mutations, and 116 (51%) had wild-type forms of NRAS and BRAF.”

ASCO 2014: Highlights for People Dealing with Melanoma

Every year, new cancer treatment insights are shared at the American Society of Clinical Oncology (ASCO) Annual Meeting. Here are some of the most notable recent developments in melanoma treatment, gleaned from researchers’ presentations at ASCO last month: Continue reading…

Two Array-Invented MEK Inhibitors Showcased At ASCO

“Two Array BioPharma-invented MEK inhibitors, binimetinib (MEK162) and selumetinib, were showcased at the 50th annual meeting of the American Society of Clinical Oncology (ASCO).  At the meeting, preliminary data for the combination of binimetinib and CDK4/6 inhibitor LEE011 (discovered by Novartis Institutes for BioMedical Research in collaboration with Astex Pharmaceuticals) from a Phase 1b/2 dose-escalation study conducted by Novartis in NRAS-mutant melanoma indicates the combination demonstrated an acceptable safety profile for most patients with promising preliminary antitumor activity.  Additionally, preliminary data for selumetinib showed favorable clinical activity in pediatric patients with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs).”

Editor’s note: This article discusses a melanoma treatment that combines two durgs: binimetinib (aka MEK162) and selumetinib. A clinical trial recently found that the combo shows promise for melanoma patients whose tumors have mutations in the NRAS gene, as detected by molecular testing. Binimetinib is also being tested as a potential treatment for patients whose tumors have mutations in the BRAF gene.

Binimetinib Continues To Advance In Clinical Development

“Three Phase 3 trials with binimetinib continue to enroll in advanced cancer patients:  NRAS-mutant melanoma (NEMO / NCT01763164), low-grade serous ovarian cancer (MILO / NCT01849874) and BRAF-mutant melanoma (COLUMBUS / NCT01909453).  NRAS-mutant melanoma represents the first potential indication for binimetinib, with a projected regulatory filing from the NRAS-mutant melanoma study estimated to be in 2015.”

Editor’s note: This is a press release from a company that is testing a new potential treatment for melanoma called binimetinib, or “MEK162.” The drug is being tested in clinical trials (learn more about clinical trials). One of the trials is enrolling melanoma patients whose tumors have mutations in the NRAS gene, as detected by molecular testing. Another is enrolling patients with BRAF mutations.

Melanoma: A 2013 ‘Progress Report’

The past year saw some remarkable advances in melanoma clinical research and treatment. This feature explores the most notable melanoma news of 2013: Continue reading…