Key Trials in Neoadjuvant I/O for ES NSCLC

Benjamin P. Levy, MD: Dr Leal, we’ve had several neoadjuvant studies that have been published or presented that are starting to look promising. Maybe you could go over some of the ones that we’ve had up to ESMO [European Society for Medical Oncology Congress], and Dr Salgia will talk about some of the neoadjuvant immunotherapy trials presented at ESMO. Can you discuss the current state of affairs for neoadjuvant immunotherapy? Just provide a high-level overview of some of these trials.

Ticiana Leal, MD: We’ve had really promising trials that have been completed on the use of preoperative nivolumab in patients with early stage non–small cell lung cancer who underwent resection following 2 doses of nivolumab. The primary end point of this study was really safety and feasibility. This was a small study. There were about 21 patients who had tumors removed. These was very interesting data because they demonstrated a very high response rate in these patients. Nine of 20 patients were resected, and they called out a major pathologic response [MPR] of 45%. That really caught everybody’s eye and interest, in regard to this strategy. Interestingly, in this study, this was independent of PD-L1 expression. In the pilot phase of the study, there was no delay in surgery. This was concluded to be something that was feasible and safe, and it really opened up the path for the up-and-coming neoadjuvant strategies we’re seeing.

Another promising strategy was the LCMC3 study, which looked at preoperative atezolizumab in resectable patients. In this study, adjuvant chemotherapy was also allowed. Again, we saw similar safety and tolerability with atezolizumab in the neoadjuvant setting. We also saw that it did not delay patients going to surgery. The major pathologic response was lower, at 19%. This was encouraging but lower than what we saw in the nivolumab study. The pathologic complete response rate was 5%. Again, the major pathologic response was independent of PD-L1 expression.

We also saw presented data on the NEOSTAR study. This randomized patients in the neoadjuvant setting to nivolumab vs nivolumab plus ipilimumab. Again, this study showed the feasibility of this approach.

As one can expect, there were higher MPR rates in the nivolumab-plus-ipilimumab arm—33% vs 17% in the nivolumab arm. I will say this study reported out that there were no unacceptable toxicities. However, there was a death on the study because of complications in the postoperative setting. This leads us to understand that, so far, there haven’t been any unacceptable toxicities. But as you roll out surgery in the post immunotherapy and immunotherapy-chemotherapy setting to general practice, the safety needs to be demonstrated better in this patient population.

Most recently, the most provocative results that have been presented are from the NADIM study. The NADIM study actually looked at a chemotherapy with I/O combination for patients in the resectable setting and showed a very high overall response rate of 78%, with a complete pathologic response in about 60% of patients. Again, it’s going back to looking at safety and tolerability and feasibility of rolling this out to practices as the data come out and really validate this end point. Certainly, the MPR end point is a very good 1 to use if it really is validated because you can get results quicker. Overall survival would be looked at in a longer study and would take more patients. So I can understand why we’re using this end point, but I would like to see that it’s a validated end point that we can trust to roll out to our patients.

Moving forward, just to summarize, neoadjuvant strategies are here to stay. I’m excited to see the results from ESMO. Chemotherapy and I/O is probably the way to go, as long as we can demonstrate safety, feasibility, no delays getting to surgery, and no increase in postoperative complications.

Benjamin P. Levy, MD: That was a very nice overview of very complicated studies. These trials are really landing front and center. I did a double or triple take with a pathologic complete response of 60% in the NADIM trial. That is quite high with just 3 cycles of chemotherapy and I/O followed by surgery. I’ll be very interested to get people’s take on that, because that’s 1 that really stood out to me, especially coming from our institution, which has done a lot of neoadjuvant studies.

Transcript Edited for Clarity

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