WCLC 2023 | Dr. Harpole: Surgical outcomes from AEGEAN trial and subgroup analyses of patients who were EGFR-mutant
Oncology Frontier: Please introduce yourself.
Dr. Harpole: I'm Dr David Harpole from Duke University in the United States. I am a thoracic surgeon, and have been doing clinical trials in lung cancer for thirty years.
Oncology Frontier: The 2023 WCLC has released the results of a number of thoracic cancer studies. Please talk about the studies that you are most interested in? What studies do you think could change clinical practice?
Dr. Harpole: This meeting has been very important to us. It is actually my favorite meeting for all oncology. It allows us to get everyone together from all over the world to discuss findings from trials from different areas and to share the data from many nations. At this meeting, I think some of the biggest advances we have seen were the role of using combination therapies for earlier stage cancers. We have been using chemotherapy/immunotherapy in advanced stages for a while, but over the last 18 months, we have seen the release of several big trial results from China, North America and globally, that have demonstrated a profound benefit for patients on what would possibly be resectable or marginally resectable tumors with amazing results of tumor shrinkage pre-resection and a high percentage of patients with their tumors completely gone with pathologic complete responses at the rate of 20-25%.
The trial I was involved with is the AEGEAN trial, which is chemotherapy and durvalumab with durvalumab after surgery versus chemotherapy alone with placebo. We presented data from that trial. The original outcomes data was supposed to take about three years, but the trial was so positive we actually had enough results demonstrating a difference in outcome at 111/2 months of followup.
We presented some of those outcomes in March at the AACR Meeting in Orlando, Florida, and at this meeting, we presented the results of the surgical outcomes and the subset of patients who were EGFR-mutant.
The summary of the surgical outcomes was that there was no safety signal for the drug with chemotherapy, both from treatment and the surgical outcomes. The surgical outcomes were excellent. In both arms, half the patients were able to have a minimally invasive approach. The recommendation for clinical trials is that whenever possible, we should try to use a minimally invasive approach (which China dominates in). If you have to convert, the outcomes for patients are still very good, but starting out with a thoracotomy is probably not recommended for patients.
The EGFR-mutated data was from a small subset of only 51 patients out of 800-plus that were on the trial (and again, a number of those came from China), and that really didn’t show a signal outcome that was advantageous for the addition of immunotherapy. There have been a number of advanced cancer studies that have shown that for those patients with EGFR mutations, immunotherapy has limited benefit, however, osimertinib and the entire tyrosine kinase family of inhibitors of EGFR have so much activity that they should be considered as primary therapy. So from the trial, we really felt that the biggest outcome was that all patients who have adenocarcinoma and for whom resection is a possibility should have EGFR testing so they can have immunotherapy after surgery, or potentially before surgery, as several of the trials from China and around the world in the last 18 months or so have suggested for these neoadjuvant approaches using EGFR-blocking drugs, such as osimertinib.