Novel Targets, Treatments Needed for Melanomas Not Responding to Targeted Immunotherapies

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Additional treatment benefits could come from the new molecules and targets in development for melanoma.
Additional treatment benefits could come from the new molecules and targets in development for melanoma.

Advancements in targeted therapies and immunotherapy have transformed the landscape of treatment for metastatic melanoma. Recent data show that as many as 70% of patients with metastatic melanoma survive for one year with the use of these novel therapies, with about half of patients achieving a long-term benefit.1

However, the other half of patients with advanced melanoma will experience disease progression. During the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, 3 experts discussed novel targets and treatment approaches for patients with metastatic melanoma during an education session entitled “Emerging Personalized Strategies in Systemic Therapy for the Treatment of Melanoma.”

Novel Combinations

“In order to increase the percentage of patients who can reach a long-term benefit, there are two possible actions,” Paolo Antonio Ascierto, MD, of Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, told Cancer Therapy Advisor. “To use effective adjuvant treatment to reduce the risk of metastases, and to improve the efficacy rate of treatments through novel combinations.”

Dr Ascierto opened the session with a discussion of novel combination therapies for melanoma.

In recent years there has been a lot of enthusiasm about the use of indoleamine 2,3-dioxygenase (IDO) inhibition. Phase 1/2 studies have shown interesting results looking at the combination of the IDO inhibitor epacadostat with pembrolizumab. However, in early 2018, Merck and Incyte announced the failure of a late-stage trial testing the combination.2

After the failure of the IDO inhibitor, the combinations of anti-programmed death (PD)-1/PD-L1 with anti-LAG-3 or with HDCA inhibitors seem promising, according to Dr Ascierto.

Other promising combinations include combining nivolumab with NKTR214 (a pegylated IL-2), and with anti-CD73, an enzyme involved in the adenosine pathway.

“The role of these combinations is to overcome primary and acquired resistance in order to continue to improve the long-term benefit in advanced melanoma patients,” Dr Ascierto said. “The promising results from the phase 1 studies with novel combination probably will continue to increase the clinical benefit in metastatic melanoma.”

However, Dr Ascierto noted that after the “revolution” in the field during the last few years, the additional benefit that will come from the new molecules will come a little at a time.

“Step by step, we will surely increase the number of patients with long-term survival,” he said.

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