Podcast 300: NADIM II trial offers “quit...

A VIDEO RECORDING OF THIS INTERVIEW IS AVAILABLE HERE.

We’re back with another interview from this year’s IASLC conference.

This time, Christine Sadlowski and Dr. Julia Rotow interview Dr. Mariano Provencio about the survival outcomes from the NADIM II trial. In that trial, patients with resectable stage III AB non-small cell lung cancer received nivolumab plus chemotherapy versus chemotherapy alone.

Overall survival at 5 years in these patients has been roughly 30%, according to Provencio. With the addition of chemo-immunotherapy, patients who showed a complete pathological response were all alive at the 3-year mark. These results, according to Rotow, are “really quite exciting.”

INTERVIEW TRANSCRIPT

Christine Sadlowski:

This is part of the NEJM Group coverage of the IASLC’s 2022 World Conference on Lung Cancer. I’m Christine Sadlowski, and with me Dr. Julia Rotow, a clinical oncologist at Dana-Farber Cancer Institute in Boston. We’re here to interview Dr. Mariano Provencio, Chair of Medical Oncology at the Hospital Universitario Puerta de Hierro Majadahonda in Madrid in Spain. He is the lead author on NADIM II, a phase 2 trial of neoadjuvant nivolumab added to chemotherapy for resectable stage III AB non-small cell lung cancer. Welcome.

Dr. Mariano Provencio:

Thank you.

Christine Sadlowski:

So first, I’d like to ask you about the history of this research because these findings come after several previous studies, including NADIM nivolumab in this clinical setting. Can you refresh us briefly on what is known so far?

Dr. Mariano Provencio:

We studied the combination with nivolumab plus chemotherapy in NADIM I. It was a clinical trial focused on stage IIIA according to the 7^th edition. It was a phase two trial. We obtained very exciting results: in overall survival, three times the historical series; in DFS [disease-free survival] around 77 percent at two years — almost double the historical series — and also early results in PCR, pathological complete response, almost 60 percent.

Then following that was the second clinical trial comparing nivolumab plus chemotherapy versus chemotherapy, and this is NADIM II.

Dr. Julia Rotow:

Thank you, Dr. Provencio. So, when you think about what we knew already in the field, could you take us through some of the key findings from the NADIM II study and what these might add to our current understanding of nivolumab in this setting?

Dr. Mariano Provencio:

In NADIM II, the primary objective was complete pathological response, and we obtained higher complete pathological response in the experimental arm. Nivo plus chemo versus chemo: Odds Ratio 7.88; p = 0.0068. We presented at the last lung cancer congress (IASLC) more progress, in PFS longer with hazard ratio of 0.48 and more overall survival hazard ratio of 0.40. And this is quite amazing results, in my opinion, comparing with chemotherapy arm.

Christine Sadlowski:

Can I go back a little bit and say in this particular presentation you’re showing primarily secondary outcomes, is that correct?

Dr. Mariano Provencio:

We presented the primary end point was a complete pathological response. It was positive and then we presented in this congress the secondary outcomes, survival outcomes, yes.

Christine Sadlowski:

And they were at 12 and 24 months, correct?

Dr. Mariano Provencio:

Correct.

Christine Sadlowski:

I was struck by the finding on overall survival. That’s obviously improved with adjuvant therapy.

Dr. Mariano Provencio:

We use adjuvant nivolumab therapy for six months. We think so, this is the first clinical trials who reported an increase in overall survival in this setting using immunotherapy plus chemotherapy and adjuvant.

Dr. Julia Rotow:

I was struck by these results. They were quite impressive. Are there any caveats we should take away from your status as secondary versus primary outcomes on the study?

Dr. Mariano Provencio:

In the first clinical trial, in NADIM I, the primary endpoint was progression-free survival. We saw pathological complete response was quite robust endpoint. I think these results are very significant in survival outcomes are very, very significant.

Christine Sadlowski:

So, what does that mean for clinical practice? I don’t actually know how nivolumab is currently used. I understand it’s approved for other cancers, not this one, but is it currently used?

Dr. Mariano Provencio:

Currently, we are using a chemo and then certainly in some cases immunotherapy, this subgroup of patients in stages 3A-B (N2) disease have poor prognostic and based on our results we can improve it. We have had the same results during last 30 years using chemotherapy and then these results are quite similar than the CM 816 specifically in stage 3A 3B. In some cases, these patients are considered with unresectable disease, and we obtain very high rate of surgery in these patients, more than 90 percent of patients underwent radical surgery is quite important to the clinical practice, in my opinion.

Our opinion, we should use chemo plus immunotherapy as standard of care in this group of patients as in the adjuvant setting.

Dr. Julia Rotow

You mentioned Checkmate 816, and I know this regimen involves a longer course of immunotherapy because of the adjuvant period. Is there anything that clinicians or patients should know about adverse effects that you saw with this regimen?

Dr. Mariano Provencio:

I think both trials are quite well tolerated results. In CM 816 we don’t use adjuvant therapy. I think maybe we have to have more results, more information about adjuvant period or adjuvant after chemo immunotherapy. Maybe in the future we’ll have to define with more detail this aspect. In any case, I think the most important part is use neoadjuvant chemo immunotherapy.

Dr. Julia Rotow:

I thought that it was great that you highlighted the surgical resection rate because it was quite a bit better with the combination chemo immunotherapy.

Dr. Mariano Provencio:

We have more than 92 percent of surgery. I mentioned before 70 percent of patients had N2 affectation. Half of them, multiple station. This is quite a high rate of radical surgery on more than 92 percent of R0 versus 60 percent in control arm. I think the surgery could be an important aspect to cure these patients.

Christine Sadlowski:

What would you need to do next to show that?

Dr. Mariano Provencio:

The next steps in this case, I think now this is a proof of concept introducing a new treatment in this group of patients. Very important this group of patients. We have almost the same survival within the last 30 years. Around 30 percent of overall survival at five years and no more than 12 or 16 months PFS. I think we have to analyze with more detail clinical trials analyzing pathological response and then in this case adjuvant treatment in these patients according to pathological response.

For example, in our study patients with PCR (complete pathological response) are 100 percent of disease-free and 100% alive at three years.

Dr. Julia Rotow:

Thank you for taking us through. I agree these are really quite exciting results and we’re so happy to have gotten to see them at the conference this year. We certainly look forward to seeing more of this sort of treatment strategy. So, thank you for joining us today.

Dr. Mariano Provencio:

Thank you.

Christine Sadlowski:

Thank you.