Patrick Forde, MBBCh, shares insights on the long-term overall survival benefit demonstrated by neoadjuvant nivolumab plus chemotherapy among patients with resectable non-small cell lung cancer, as seen in the CheckMate 816 trial.

With updated results and a median follow-up of 68 months, there was a statistically significant overall survival benefit seen with neoadjuvant nivolumab plus chemotherapy compared with chemotherapy alone. The 5-year overall survival rate was 65% vs 55%, respectively, and the nivolumab plus chemotherapy regimen was favored in subgroups defined by tumor PD-L1 expression, baseline disease stage, and histology.

These results were first presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript:

My name is Patrick Ford. I'm a professor and chair of immuno-oncology at Trinity College Dublin at back in Ireland, and today I'm at the ASCO 2025 conference. This weekend I'm presenting the 5-year survival results of the CheckMate 816 trial.

This was a trial which was originally presented back in 2021, with data on pathologic complete response rate, showing a significant improvement from the addition of nivolumab to standard neoadjuvant chemotherapy and pathologic complete response. Then subsequently in 2022, we showed that event-free survival, which is a key surrogate end point in early-stage lung cancer, was also significantly improved from those 3 cycles of neoadjuvant therapy.

The update this weekend is the final overall survival results, and in the study I presented, the addition of 3 cycles of nivolumab to standard chemo[therapy] in the neoadjuvant setting delivers approximately a 10% improvement in 5-year survival for patients with stage 1B to 3 non-small cell lung cancer. And in addition to that, there was a key finding regarding pathologic response. Those patients who have a pathologic complete response to neoadjuvant nivolumab plus chemotherapy, approximately 24% of the patients had that response and none of those patients had died from lung cancer by the 5-year mark. Whereas, unfortunately, many patients who did not have a pathologic complete response had passed away. So that potentially indicates that pathologic complete response could be a very good prognostic indicator for those patients who receive neoadjuvant chemo with immunotherapy.

The other interesting point was those patients who cleared circulating tumor DNA, measured prior to the first dose of neoadjuvant therapy and again prior to the third dose of neoadjuvant therapy, they also had a better outcome compared to those patients who did not clear circulating tumor DNA. So that's another potential prognostic, or even in the longer-term, predictive marker of benefit from neoadjuvant therapy.

And to put these results in context, we now have 1 phase 3 neoadjuvant-only trial, CheckMate 816, which shows an overall survival benefit. We also have a perioperative, being neoadjuvant chemoimmunotherapy followed by adjuvant immunotherapy, trial, KEYNOTE-671, that also shows an overall survival benefit.

I think one of the key questions for oncologists is going to be how do we decide between neoadjuvant-only therapy and perioperative therapy? There are clinical trials ongoing, in particular a trial called ADOPT-lung being run in Europe, which is trying to tease out that question, but it'll take several years for that to result out. In the meantime, I think we're going to probably have to look at the subgroups in the trials. Perhaps those patients who don't have a pathologic complete response might benefit from further therapy or perhaps those patients who have a higher risk of disease, so perhaps PD-L1–negative disease in particular. 

That’s the summary of the results from the trial, and the trial was also published in the New England Journal of Medicine this weekend.

Source:

Forde P, Spicer J, Provencio M, et al. Overall survival with neoadjuvant nivolumab (NIVO) + chemotherapy (chemo) in patients with resectable NSCLC in CheckMate 816. Presented at the 2025 ASCO Annual Meeting. May 30-June 3; Chicago, IL. Abstract: LBA8000