Adjuvant Checkpoint Inhibitors in Resectable NSCLC

Nasser Altorki, MD, Weill Cornell Medical College, New York, reviews his presentation on adjuvant checkpoint inhibitors for patients with resectable non-small cell lung cancer, from the 2022 Great Debates and Updates in Lung Cancer meeting in New York.

Transcript:

My name is Nasser Altorki. I'm the chief of thoracic surgery at Weill Cornell Medicine at New York Presbyterian Hospital in New York. We just finished a session of Great Debates and Updates in Lung Cancer discussing neoadjuvant and adjuvant immunotherapy in early stage disease. What is clear is the field has been completely transformed in the last 4 years. There are at least 4 adjuvant trials of immunotherapy in early stage disease. Two have reported results and two have yet to report. The first to report is Empower-010, which tested adjuvant atezolizumab after chemotherapy in patients who were completely resected, so had an R0 resection, and received up to 4 cycles of chemotherapy. The primary end point of the trial was progression-free survival in patients with PD-L1 expression and stage 2/3A non-small cell lung cancer. For that, there was a significant improvement in survival in patients who had atezolizumab versus best supportive care, and the drug was in fact approved by the FDA for that indication. The trial continues in follow-up for disease-free survival in the overall intention-to-treat population, that includes patients with stage 1B, and for overall survival.

The other trial that reported is the PEARLS trial, which is essentially adjuvant pembrolizumab. Here, the trial uses the same indication, which is patients who have received a completely resection. The adjuvant chemotherapy was recommended but not mandated, and the trial had 2 co-primary end points: progression-free survival and disease-free survival regardless of PD-L1 expression, and disease-free survival in patients who have ≥50%expression of PD-L1 in their primary tumor. The primary end point showed the disease-free survival was superior to placebo regardless of PD-L1 expression. But the confusing result was, in those that expressed ≥50% PD-L1, there was no difference in survival between the two groups. There is no FDA approval yet, and it's still early so we might still see a benefit in that subgroup, so we'll wait and see what the final outcome of that is. The trial has been reported recently in Lancet Oncology. There are 2 other adjuvant trials that have not yet reported results, and will help clarify matters a little bit more.

There are also 4 ongoing neoadjuvant trials of immunotherapy plus chemotherapy in non-small cell lung cancer. The first to report completely is Checkmate-816, which used 3 cycles of neoadjuvant platinum-based chemotherapy plus nivolumab compared to 3 cycles of platinum-based chemotherapy alone, no adjuvant components, in stage 1B-3A disease. The results are clearly showing that the complete pathological response is superior with the triple regimen than with chemotherapy alone, 24% versus 2%, event-free survival was superior in the nivolumab-chemotherapy arm as well as overall survival, and there is an FDA approval for the use of that as a standard of care in the neoadjuvant setting, mainly driven really by the patients with high PD-L1 expression and patients with stage 3A disease.

Another trial, on which there was a press release but no formal report, is the AGN trial, which is a combination of chemotherapy plus durvalumab versus chemotherapy alone. The press release stated that there was a significant benefit in complete pathological response. The co-primary end point of event-free survival is still blinded. We'll probably learn more about it in the next few months.

The 2 other neoadjuvant trials that are ongoing and will hopefully report within the next 12 to 18 months, and then we will have an embarrassment of riches trying to figure out which patients will benefit from adjuvant therapy, which patients will benefit from neoadjuvant therapy. It's a discussion that  surgeons and oncologists are having right now, primarily because we don't have perfect biomarkers in that space. But it's very exciting and there is definitely a change in the outcomes associated early stage disease.
 

Source:

Altorki N. Adjuvant checkpoint inhibitors in resectable NSCLC. Presented at: Great Debates and Updates in Lung Cancer; October 14-15, 2022; Brooklyn, New York.