麻豆传媒

The addition of neoadjuvant nivolumab (Opdivo) to chemotherapy significantly improved outcomes in patients with resectable stage IIIA non-small cell lung cancer, according to results from the NADIM II trial. The new data were presented at the recent World Conference on Lung Cancer (WCLC).

In this exclusive 麻豆传媒 video, Nicholas Rohs, MD, of the Icahn School of Medicine at Mount Sinai in New York City, highlights the results of this study.

Following is a transcript of his remarks:

There's been a flurry of exciting data in the neoadjuvant space recently. We just had the CheckMate-816 trial come out, but what was really presented at the World Lung Conference this year was the NADIM II trial.

So, this is a trial that follows up on the original NADIM trial. And this is looking at chemotherapy plus nivolumab, or Opdivo, in the neoadjuvant space. This was an open-label, phase II, multicenter clinical trial with resectable stage IIIA non-small cell lung cancer. So this was not stage I/II, this was stage IIIA non-small cell lung cancer patients with a maintained performance status and negative for EGFR/ALK mutations, randomized to nivolumab 360 mg with carboplatin and paclitaxel versus chemotherapy alone. Every 21 days in the patients who had an R0 resection and were randomized in the nivolumab arm also continued with some adjuvant nivolumab, about 3 to 8 weeks after surgery for up to 6 months.

So, this was resectable stage IIIA non-small cell lung cancer, and at 26.1 months what we're seeing is that this is really showing some impactful changes for this patient population. They have a progression-free survival improvement by about 52% compared to the chemotherapy-alone arm. We saw the PFS at 12 months was 89% versus 60%, but at 24 months that gap continues -- the PFS being 66% versus 43% in the nivolumab versus the non-immunotherapy arm. And this was also reflected in the overall survival data. What we see is 98.2% of patients in the immunotherapy arm were alive versus 82.1% at 12 months. And again, continued to show benefit at 24 months, with an overall survival rate of 84.7% versus 63.4%, with a really solid hazard ratio of 0.4.

And a really interesting part of that data is patients who had a pathological complete response after this treatment, all of those patients were alive at the data cutoff for this presentation. So it really seems that that's very indicative of benefit for these patients.

And, you know, of course the data's really exciting here, but one of the discussions we have around in this space is, well, if we're giving somebody neoadjuvant therapy, are we delaying their ability to make it to surgery? Are we making their surgeries more difficult? How is this affecting their ability to get to the operating room and get these tumors removed? And surprisingly, we actually saw patients in the chemoimmunotherapy arm do better. They got to surgery 93% of the time, with the chemotherapy-alone arm only getting to surgery 69% of the time. And R0 resections were more likely -- 92.5% versus 65%. So really exciting and interesting to see that patients who had immunotherapy added onto their treatment actually got better surgery, or are more likely to have surgery is probably a better way to put it.

And again, similar to other trials we've seen is that PD-L1-positive tumors were driving most of this benefit, the more PD-L1 expression we had, the better these patients are doing. But this data is still maturing, particularly overall survival data. So we still have some more space to see where this is all playing out and exactly which subpopulations are going to benefit the most and where our cutoff should be.

But this data paired with CheckMate-816, really in my practice, cements neoadjuvant therapy, particularly chemoimmunotherapy combinations, as a new standard of care for many of the patient populations in this group, particularly immune-positive, genetic-negative patients.

And what people are talking about once this data came out, again, because this is for stage III patients -- it's going to be really interesting if we can put together a trial that looks at surgical versus nonsurgical interventions for these patient populations, because it's always a hot debate. Should this patient be going to chemoradiation, should they go to surgery? And there's probably going to be some nuances we're going to find out about which population should go where.

And I'd say the one other thing I'd highlight about this study is the liquid biopsy data. So, there's cell-free or circulating tumor DNA [ctDNA] data. Again, we're seeing that patients who clear their ctDNA are doing better than those who do not. And those who do not clear their circulating tumor DNA probably need some other form of therapy.

And I guess the one last thing I bring up about this is, this study was done at a lot of academic centers with really good resources and good interdisciplinary care. And the question is, is this going to be applicable to non-academic centers where maybe the resources aren't as centralized? I really hope so. I think that this is such a meaningful change in our patients' care planning that hopefully this is something that can be executed at all centers across the globe, as we learn more and as this becomes more in our day-to-day lexicon of how we approach our patients.

And it just speaks to the need for us to continue to work on getting really rapid, reliable genetic and immune testing for these patients to make sure we know which patients should be going in what direction for their best care treatment pathways. And of course we're always looking for better biomarkers than PD-L1, but for right now, that's what we have and that's what's going to lead us in the right directions as best as we can.

So again, a really exciting World Lung Cancer Conference in Vienna, Austria, this year. Some really exciting data, particularly in early-stage lung cancers. Always a meeting I'm excited to join in and learn more, and hopefully we'll continue to learn more as we go along.

Comment