PD-1 Blockers Improve Survival in Melanoma, With Lowest Risk of Side Effects

MedicalResearch.com Interview with:

Feng Xie, Ph.D.</strong> Associate Professor Department of Clinical Epidemiology and Biostatistics Faculty of Health Sciences, McMaster University

Dr. Feng Xie

Feng Xie, Ph.D.
Associate Professor
Department of Clinical Epidemiology and Biostatistics
Faculty of Health Sciences
McMaster University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Cutaneous melanoma, an aggressive and deadly form of skin cancer, in early stages is often cured with surgery alone. Most patients presenting with advanced-stage disease, however, are not candidates for surgery and drug therapy is the main course of treatment. Around 40-60% of melanomas have a mutation in the BRAF protein. Multiple effective first-line treatment options are available for patients with advanced BRAF-mutated melanoma, which fall under two established classes of drug therapies: targeted therapy and immunotherapy. Presently, it remains uncertain which is the optimal first-line treatment.

In our network meta-analysis we evaluated 15 randomized controlled trials published between 2011 and 2015 assessing the benefits and harms of targeted or immune checkpoint inhibitors in 6662 treatment naïve patients with lymph node metastasis not amenable to surgery or distant metastatic melanoma.

We found that combined BRAF and MEK targeted therapy and PD-1 immunotherapy were both equally effective in improving overall survival. Combined BRAF and MEK inhibition was most effective in improving progression-free survival. PD-1 inhibition was associated with the lowest risk of serious adverse events.

MedicalResearch.com: What should readers take away from your report?

Response: The most important message from this work is that PD-1 was effective in improving overall survival and also associated with lower risk of serious adverse events for melanoma patients. The PD-1 immunotherapy has demonstrated superior in terms of these two important outcome measures for cancer patients.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Our review and network meta-analysis was based on the class of therapy. With the evidence accumulating, the next step should be to assess comparative effectiveness profiles of individual PD-1 therapies and cost effectiveness among these therapies. Our finding can also be informative to future clinical trial design in terms of the selection of comparators.

MedicalResearch.com: Is there anything else you would like to add?

Response: We should focus on the effect of cancer therapy on survival and quality of survival.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.


Devji T, Levine O, Neupane B, Beyene J, Xie F. Systemic Therapy for Previously Untreated Advanced BRAF-Mutated MelanomaA Systematic Review and Network Meta-Analysis of Randomized Clinical Trials. JAMA Oncol. Published online October 27, 2016. doi:10.1001/jamaoncol.2016.4877


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