What’s New in Melanoma Treatment in 2019?


It has been over a year since I last wrote about new developments in treatment of melanoma, and it is time for an update. There is certainly some good news for melanoma patients!

Neoadjuvant (before surgery) treatments for resectable melanoma

Stage III—and more rarely, stage IV—melanoma tumors that have not spread widely can be sometimes treated surgically. Last year a small clinical trial showed that, in BRAF-mutant melanoma, treatment with the BRAF/MEK inhibitors dabrafenib and trametinib (D/T) before and after surgery provides a significant improvement over just post-surgery treatment, by preventing later recurrence.

Later in 2018, researchers reported that using the immune checkpoint drugs nivolumab and ipilimumab prior to surgery led to tumor reduction in 73% of patients treated in a clinical trial. After surgery, they remained disease-free for 2 years (the reported time of observation). Treatment with nivolumab alone was not nearly as active in this randomized trial, with only 25% of patients responding to neoadjuvant nivolumab; still, 75% were disease-free within the 2-year observation period.

An interesting trial tested a single dose of the drug pembrolizumab given three weeks prior to surgery. Of 27 patients who received this single infusion, eight (29%) had a complete or major pathological response, meaning that their tumors were reduced by 90% or more. These eight patients continued on pembrolizumab after surgery and were disease-free for over 2 years. Continue reading…


Could Adding a TLR9 Agonist Improve Responses in Metastatic Melanoma?

Excerpt:

“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.”

Go to full article.

If you’re wondering whether this story applies to your own cancer case or a loved one’s, we invite you to use our ASK Cancer Commons service.


TLR9 Agonist CMP-001-Pembrolizumab Combination Shows Early Efficacy for Metastatic Melanoma Resistant to Anti-PD-1

Excerpt:

A combination of CMP-001, an intratumoral Toll-like receptor 9 (TLR9) agonist, and pembrolizumab (Keytruda), tested in patients with metastatic melanoma resistant to PD-1 checkpoint inhibition, was well tolerated and had clinical activity according to preliminary data presented from the ongoing phase Ib clinical trial at the AACR Annual Meeting 2018, April 14-18, in Chicago.

” ‘Checkpoint inhibition is quickly becoming a key tool for oncologists to treat cancer,’ said Mohammed Milhem, MBBS, clinical professor of internal medicine at the University of Iowa, Iowa City. ‘However, there are many  that either initially respond to checkpoint inhibition and then progress, or never respond to this therapy to begin with. Finding safe and effective therapies for these patients is critical.’ ”

Go to full article.

If you’re wondering whether this story applies to your own cancer case or a loved one’s, we invite you to use our ASK Cancer Commons service.


Depleting Tumor-Specific Tregs at a Single Site Eradicates Disseminated Tumors

“Activation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, Tregs eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40.”


Depleting Tumor-Specific Tregs at a Single Site Eradicates Disseminated Tumors

“Activation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, Tregs eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40.”


Depleting Tumor-Specific Tregs at a Single Site Eradicates Disseminated Tumors

“Activation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, Tregs eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40.”