Hi, I'm Dr. Suresh Ramalingam from the Winship Cancer Institute of Emory University. I'm excited to talk about the results of the CheckMate 227 trial that we just reported at the ASCO 2020 virtual meeting earlier today. As you are aware of, there are some many exciting developments happening in lung cancer including some of the key abstracts you're going to hear from at this meeting.
Specifically, the CheckMate 227 trial was designed to look at the role of ipilimumab and nivolumab in frontline treatment of advanced stage non-small cell lung cancer. A very large trial of close to 1800 patients were enrolled. We randomized patients who had high PD-L1 expression, which is defined as greater than 1% to chemo versus nivo versus ipi plus nivo.
And patients with PD-L1 expression less than 1%-- we randomized them to chemo versus chemo plus nivo and ipi plus nivo. We've already reported the overall survival results of the trial in the New England Journal not too long ago.
At this meeting, we are reporting longer follow up with three year survival rates for the study population. The trial, when you look at just the nivo-ipi versus chemo comparison which I think is the most germane given what we are presenting, had 583 patients in each group.
This included a third of the patients with PD-L1 expression greater than 50%. Another third of the patients with PD-L1 expression less than 30%. And about 28% of the patients had squamous cell histology. Good balance and baseline characteristics between the nivo- ipi group and the chemo group.
What we're showing here is that the three year overall survival rate with nivo and ipi was 33% for the PD-L1 greater than 1% population and 22% with chemotherapy. The fact that a third of the patients were alive at three years with nivo plus ipi is a substantial improvement over what we used to have with lung cancer treatments not too long ago.
In the PD-L1 less than 1% group, we saw that the three year survival rate with nivo plus ipi was 34% compared to 15% with chemotherapy alone. So we saw the strong signal of favorable three year outcomes both in PD-L1 high and PD-L1 negative patients in the CheckMate 227 trial.
We were also excited about the duration of response with nivo and ipi. It was 23 months with nivo and ipi in the PD-L1 greater than 1% group compared to only about 6 and 1/2 months with chemotherapy. When you look at the PD-L1 low group, there again, the median duration of response was 18 months with nivo plus ipi compared to 4 and 1/2 months with chemotherapy.
The third point I want to make about this is we conducted a landmark analysis. We looked at, what is the best response six months from the time of starting treatment? And compared that with what the long term outcome for those patients are.
What was exciting to us is, if by six months a patient has a complete response or a partial response with nivo and ipi, the three year survival rate was 70% for the PD-L1 greater than 1% group and 82% for the PD-L1 expression less than 1% group. So these are very robust results that show that patients who achieve a response maintain it and perhaps contribute to the tail of the curve.
We didn't see a long term effect in the patients who experienced stable disease or progression of disease-- the response that predicts better long term survival with the nivo and ipi. And finally, the combination was tolerated well. Most of the adverse events happen in the first six months.
And these were managed with appropriate supportive care and other measures. And after that six month period, the incidents of autoimmune adverse events were relatively small. So overall what we're reporting here is, the three year survival rate with nivo plus ipi in the frontline setting is approximately 33%-- 34%, the median duration of response is considerably longer than chemotherapy, and patients who achieve a complete response-- a partial response for six months have a greater than 70% likelihood of surviving for two years after the six month landmark.
And overall, these results confirm the use of nivo and ipi as an effective frontline option for non-small cell lung cancer patients. Indeed just two weeks ago, the US FDA has approved nivo plus ipi in the frontline setting for the PD-L1 greater than 1% population. So summary is, this is a new effective frontline therapy regiment for advanced stage non-small cell lung cancer patients who do not have a driver mutation that is amenable to targeted therapy.
How will physicians chose from the available options?
I think it's good to have options for our patients. This helps us narrow down any individualized treatment options for patients based on multiple factors including patient baseline information, comorbid conditions, patient expectations, presence or absence of important immune related diseases that could influence our treatment decisions, and so forth.
So where do I see this going? I think for patients with PD-L1 expression greater than 50%, we would continue to use pembro monotherapy, and more recently atezolizumab has joined the list. For patients with PD-L1 expression less than 50% where we are now using chemo plus pembro as a standard approach, the ipi plus nivo regimen would be very reasonable and evidence based approach. Specifically, if patients don't want to go through chemotherapy, this would be definitely worth consideration in our practice.
What are the key unanswered questions?
I think our goal continues to be to improve the percentage of patients who benefit from immunotherapy. And also to lengthen the duration of benefit. So I believe that novel combinations building on existing standard paradigms will continue to be the focus of investigation.
We know that at the end of the day with immunotherapy, durable benefits are seen in only about 30% of the patients. We need better options for the other 2/3 of the patients. And that's what we and others are working on.