Immunotherapy Effective Against Hereditary Melanoma

Excerpt:

Individuals with an inherited form of skin cancer often have a poor prognosis. The type of immunotherapy that was awarded this year’s Nobel Prize in Physiology or Medicine is, however, particularly effective in this patient group, research from Karolinska Institutet in Sweden shows. The study is published in the Journal of Medical Genetics.

“Congenital mutations of the CDKN2A gene are the strongest known risk factors for inherited . Individuals with  who carry mutations in this gene also have , according to previous research.”

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Dual Neoadjuvant Checkpoint Blockade Feasible in Melanoma

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“Combination neoadjuvant immune checkpoint blockade therapy yielded promising outcomes in high-risk resectable melanoma, although toxicity was an issue, according to a phase II trial.

“The combination of ipilimumab (Yervoy) and nivolumab (Opdivo) led to improved progression-free survival (PFS), distant metastasis-free survival (DMFS), and overall survival (OS) versus neoadjuvant nivolumab monotherapy in 23 patients with high-risk resectable melanoma, reported Jennifer A. Wargo, MD, of MD Anderson Cancer Center in Houston, and colleagues in Nature Medicine.”

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BRAF-MEK Inhibitor Combo Extends Survival n BRAF-Mutant Melanoma

Excerpt:

“The combination of encorafenib and binimetinib resulted in longer overall survival (OS) compared with vemurafenib in patients with BRAF V600–mutant melanoma, according to results of the COLUMBUS trial. Combined with an earlier report showing improved progression-free survival (PFS), this suggests the regimen should become an important option in this setting.

“Small-molecule BRAF inhibitors, originally introduced as monotherapy, offered improvements in outcomes for these melanoma patients. ‘However, response durations were short and BRAF inhibitor treatment was associated with the development of squamous cell skin cancer and other skin toxicities related to paradoxical MAPK pathway activation,’ wrote study authors led by Reinhard Dummer, MD, of University Hospital Zurich in Switzerland. Combinations of BRAF and MEK inhibition have improved the situation further, but better treatment options are still needed.”

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Could Adding a TLR9 Agonist Improve Responses in Metastatic Melanoma?

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“A phase I trial found promising activity and good tolerability with the combination of pembrolizumab and a stimulant of Toll-like receptor 9 (TLR9) known as SD-101 in patients with unresectable or metastatic melanoma, particularly in those who had not received prior anti–programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy.

“PD-1/PD-L1 inhibition has improved outcomes in metastatic melanoma, and studies have indicated that combination therapy can increase immune responses further. “Despite the improvement in response rates with combination immunotherapy, a large unmet need remains,” wrote study authors led by Antoni Ribas, MD, PhD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center.”

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Overall Survival Improved With Encorafenib/Binimetinib Combination in BRAF-Mutant Melanoma

Excerpt:

In patients with advanced BRAF V600–mutant melanoma, combining the BRAF inhibitor encorafenib (Braftovi) with the MEK inhibitor binimetinib (Mektovi) improved overall survival compared to vemurafenib (Zelboraf) or encorafenib as monotherapy, with a favorable toxicity profile, according to updated results from the phase III COLUMBUS trial.

“Combined BRAF/MEK inhibitor therapy is standard of care in advanced BRAF V600–mutant melanoma, but approved combinations have unique toxicities that may impact the ability to deliver optimal treatment (ie, vemurafenib/cobimetinib [Cotellic] is associated with photosensitivity).”

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Dual Immunotherapy a Winner for Melanoma Brain Mets

Excerpt:

“Combined immunotherapy with two checkpoint inhibitors — nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) — has shown ‘clinically meaningful’ efficacy in patients with asymptomatic, untreated melanoma metastases to the brain, according to a report regarding new data from the CheckMate 204 open-label phase 2 study.

” ‘Although current practice is to start with surgery, stereotactic radiotherapy, or both followed by immunotherapy or targeted agents, our results support the initiation of immunotherapy to achieve prompt control of both extracranial and brain metastases,’ write the authors.”

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ASCO and Friends Submit Recommendations to FDA Aimed at Reducing Barriers to Clinical Trial Participation

Excerpt:

“ASCO and Friends of Cancer Research (Friends) have submitted recommended language to the U.S. Food and Drug Administration (FDA) for five guidance documents on ways to broaden eligibility criteria for cancer clinical trials. The recommendations are part of an ASCO and Friends collaboration to broaden eligibility for participating in clinical trials by addressing five specific areas: minimum age requirements for trial enrollment, HIV/AIDS status, brain metastases, organ dysfunction, and prior and concurrent malignancies.”

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Immune-Based Therapy May Be Tool Against Melanoma in the Brain

Excerpt:

“A type of therapy that harnesses the immune system is giving new hope to people battling a once hopeless cancer — melanoma that’s spread to the brain.

“New research involving more than 2,700 U.S. patients is confirming what specialists in the field have long known — that “checkpoint blockade” treatment can beat back these devastating tumors.”

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