Once again, a drug that enhances a patient’s own immune system has shown a marked improvement in tumour regression as compared to standard chemotherapy regimens in the treatment of advanced melanoma.
Just as with the recent successes seen for its immunotherapy agent, Yervoy (ipilimumab), which blocks a receptor called CTLA-4, Bristol-Myers Squibb’s new drug Opdivo (nivolumab) has shown deep and durable responses in patients with advanced melanoma who have progressed after standard treatment with BRAF inhibitors or Yervoy – in other words, patients who have few other treatment options.
“This is a highly favourable outcome,” said Jeffrey Weber of the Moffitt Cancer Center in Florida, reporting the results for nivolumab at the European Society of Medical Oncology meeting in Madrid.
Nivolumab, a monoclonal antibody, works by blocking the interaction between a receptor called PD-1 (programmed cell death-1) which is expressed on T-cells, and the receptor’s ligand, PDL-1, expressed by tumours.
“In a state of chronic antigenic stimulation, like that chronic infection, or cancer, this receptor is highly up-regulated and tends to suppress the immune system,” Dr Weber explained. When this heightened expression occurs immunologists refer to it as “immune exhaustion”.
“At this point, the immune system no longer works adequately, and certainly not well enough to eliminate tumours,” said Dr Weber. “If we can block this receptor/ligand interaction it’s hoped that it will allow the immune system to proceed in an unfettered manner.”
Prior to this study, nivolumab had already shown promise in a variety of tumour types, including kidney cancer and non-small cell lung cancer, as well as melanoma.
In the present Phase III study, nivolumab was compared to a standard-of-care “physician’s choice” which in this case could either be dacarbazine (favoured in Europe) or a combination of carboplatin/paclitaxel (as used in the USA).
The trial enrolled 405 patients with advanced melanoma who had previously been treated with Yervoy but then experienced disease progression.
The study endpoint was overall response rate, and treatment was scheduled to continue until patients experienced disease progression.
Impressive response rates
As reported by Dr Weber, the data were impressive. “There was a response rate of 32% for nivolumab versus 11% for physician’s choice,” he said. “And 95% of those responses are ongoing – the median duration of response hasn’t been reached.” The median duration of response to chemotherapy was 3.5 months.
Interestingly, responses were seen regardless of the patient’s pre-treatment PD-L1 expression status – interesting because the meaning of this observation is not clear (it’s been noted before) and is the subject of an ongoing debate in the oncology community.
Adverse events favoured the nivolumab treatment arm, and were considered manageable.
Survival data will be reported in the future as the study matures, however, should there be any doubt about the impact of this preliminary report, Dr Weber offered this: “In my view nivolumab should replace chemotherapy in routine practice in second or third line treatment for melanoma patients.”