Melanoma is one of the most treatable cancers with immunotherapy. It was the first cancer for which a checkpoint inhibitor immunotherapy―the anti-CTLA-4 antibody ipilimumab―received FDA approval.
In the five years since that approval, the anti-PD-1 checkpoint antibodies nivolumab and pembrolizumab, as well as the combination of nivolumab and ipilimumab, have also been approved for melanoma, helping improve patient survival rates to historical highs, and many other approaches have since shown promise against this disease.
Earlier at ASCO16, we highlighted approaches that combined checkpoint immunotherapies with conventional treatments, such as chemotherapy and radiation. We also explored some novel immunotherapy strategies against melanoma, including the use of an anti-inflammatory cytokine as well as a bi-specific antibody that acts as a matchmaker for killer T cells and cancer cells. This second approach is especially promising, as it also worked against uveal melanoma, a distinct type of melanoma of the eye, against which single-agent checkpoint immunotherapy has failed.
As ASCO16 began to wrap, the talks hearkened back to the basics. Our coverage will now follow suit by looking long-term impact of checkpoint inhibitors in melanoma patients.
First, Caroline Robert, M.D., Ph.D. discussed work conducted with Jedd Wolchok, M.D., Ph.D., an associate director of CRI’s Scientific Advisory Council, and Antoni Ribas, M.D. Ph.D., a member of the leadership team of CRI’s clinical program and a co-investigator on the CRI-SU2C Cancer Immunology Translational Research Dream Team. Robert showed that melanoma patients treated with the anti-PD-1 checkpoint antibody pembrolizumab had superior long-term rates of overall survival as well as survival without their disease progressing, compared to chemotherapy-treated patients. After three years, 40% of pembrolizumab-treated patients are still alive, and had a median overall survival of almost two years.
Further advantages of pembrolizumab in melanoma were next highlighted by Jacob Schachter, M.D., of the Ella Institute for Treatment and Research of Melanoma and Skin Cancer in Israel. In work conducted with Ribas and Georgina Long, Ph.D., whom CRI currently funds, pembrolizumab led to responses in 36% of patients, more than twice the rate (13%) of ipilimumab. Fortunately, both treatments led to benefits: more than 40% of patients survived at least two years no matter which immunotherapy they received.
Next, Wolchok, who is the chief of the Melanoma & Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center, spoke. As the lead investigator of the study that led to ipilimumab’s initial approval, Wolchok is a central figure in this immunotherapy revolution, and revealed the benefits of combining nivolumab and ipilimumab. Regardless of a patient’s status with respect to mutations or PD-L1 expression, that combination led to improved progression-free survival compared to either immunotherapy alone.
Unfortunately, we’d previously known about the additional toxicity associated with the above combination. Fortunately, some scientists―such as those conducted by Long and Ribas, as well as Jonathan Cebon, Ph.D., another member of the leadership team of CRI’s clinical program―have worked to improve upon that. In their work, they showed that combining specific doses of pembrolizumab and ipilimumab could not only provide patients with potent anti-tumor responses, but also do so in a safer and more tolerable way. This study is not the only one looking at how to combine immunotherapies in the smartest, safest possible way, and with so many competent scientists and doctors tackling this challenge, it gives us a great chance to continue improving survival even more in melanoma patients.