KEYNOTE-716 is the global randomised phase III placebo-controlled clinical trial that demonstrated superiority of pembrolizumab over placebo in patients with stage 2b and 2c melanoma. This was a study that we reported out initially two years ago where it met its primary endpoint for recurrence free survival at the first protocol-specified analysis of 12 months. It has subsequently been updated a couple of times.
At ASCO, we’re updating the 36-month landmark evaluation for distant metastasis free survival. This is the final protocol-specified analysis. The data is quite promising in showing that the benefits of pembrolizumab, in fact, is getting greater over time, as we would actually expect, but emphasising the point that these patients with stage 2b and 2c melanoma are at very high risk of recurrence, and that pembrolizumab reduces that risk of recurrence by 41%, as of the update here at the meeting.
So those are important data when we engage with patients about whether or not they would choose to take adjuvant therapy. Of course, it’s always with the trade-off of any side effects that the patient might have. Pembrolizumab has a well-known side effect profile with about 5% very serious, irreversible toxicities, and up to 20% thyroid-related events, etc, so it is something that patients have to think through. The study has been really, really important, however, in changing the perspective in the melanoma oncology community about what constitutes high-risk disease after surgery.
So, historically we thought of patients who had lymph nodes involved being those who had the highest risk of recurrence, but when you actually looked at actual outcomes, it turns out that the patients who had deep primary lesions, so the stage 2 patients with deep primaries, in fact, did worse than the patients who only had one lymph node. Yet, for many years we did not have access to adjuvant therapy for those patients, and that’s what KEYNOTE-716 really levels at the field. I think these data now are going to be a springboard as we go forward in melanoma oncology. There are four randomised phase III clinical trials of immunotherapy combination studies for adjuvant therapy coming, and those studies now all include the stage 2 population, which we demonstrated in KEYNOTE-716, also benefit from immunotherapy.
The long-term results that we shared today showed that there is a big benefit to pembro, and really just kind of set the stage for even more success in melanoma moving into the future.