At the 2023 World Conference on Lung Cancer, Tetsuya Mitsudomi, MD, PhD, Kindai University, Osaka-Sayama, Japan, presented results from the phase 3 AEGEAN study which demonstrated the addition of perioperative durvalumab to neoadjuvant chemotherapy did not adversely affect surgical outcomes, and led to numerically higher R0 resection rates among patients with resectable non-small cell lung cancer.

Transcript:

Hi everyone, my name is Tetsuya Mitsudomi from Kindai University [and] I'm a thoracic surgeon. This time I presented surgical outcomes of the AEGEAN trial, which is the phase 3 randomized study comparing perioperative durvalumab plus neoadjuvant chemotherapy versus neoadjuvant chemotherapy alone.

The primary analysis of this trial was already presented in April of this year at the AACR [American Association for Cancer Research] meeting by Dr John Hemach [MD, The University of Texas MD Anderson Cancer Center, Houston, Texas]. The primarily endpoint was event-free survival (EFS) and pathological complete response (PCR). The MET-free survival hazard ratio was 0.68, and pathological complete response was about 14% in the durvalumab arm versus 4% in the control arm, meaning that the perioperative durvalumab plus post-operative durvalumab to neoadjuvant chemotherapy.

This time, I presented how this addition of perioperative durvalumab affects surgical outcomes. First, there were about 740 patients in the MITT population, where MITT means modified intention to treat, excluding the 50-some patients with EGFR authorizing because these patients are thought to be nonresponsive to the immune checkpoint inhibitors. Those patients are randomized between the 2 arms and of them, about 20% of the patients did not complete the surgery, meaning that those patients did not have their tumor resected but 20% of the patients, number is not so small, but it's comparable to the previous neoadjuvant [immunotherapy] IO trials. Then we cut several surgical parameters such as delay in surgery, or interval between the neoadjuvant therapy to the surgery, or surgery to the post-operative adjuvant therapy initiation and again there are no difference between the durvalumab arm and control chemotherapy placebo arm.  

Then we looked at surgical duration, which was about 3 hours and some minutes so it's the same between the 2 arms and in terms of the operative procedures, about half were open procedure, about half were minimal invasive procedure. Again, the incidence of those procedures are similar between the two arms. Less than 90% of the patients underwent lobectomies, including bi-lobectomies and discrete resection and about 10% of patients received pneumonectomy but this instance is also similar between the 2 arms.

When you look at the advancements, the instance of advancement was not affected by the treatment arm. Also, the instance of the complications and severity of the complications were not affected by the treatment arm. What we found was R0 resection — R0 resection means that there's no remnant tumor behind, complete pathologic complete resection, the instance of the R0 resection was slightly numerically higher in the durvalumab arm compared to the control arm [and] maybe that's one of the reasons why the EFS and PCR is higher in the durvalumab arm.

In conclusion, it has been already shown that the event-free survival on the PCR is greatly improved by addition of the perioperative durvalumab, plus neoadjuvant chemotherapy. Now, we are able to show that those new modality of treatment did not adversely affect any of the surgical parameters. Yet, we found a numerically higher R0 resection rate by adding the perioperative durvalumab, and those toxicities are also manageable, which is not different from the control arm. In addition to the efficacy results, no adverse effect on the surgical outcomes.

We can now say that this [AEGEAN] regimen, perioperative durvalumab plus chemotherapy, neoadjuvant chemotherapy surgery, followed by surgery, followed by adjuvant durvalumab could be one viable option for patients with stage 2 to 3/3B non-small cell lung cancers.

Source:

Mitsudomi T, Heymach JV, Reck M, et al. Surgical outcomes with neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab in resectable NSCLC (AEGEAN). Presented at the 2023 World Conference on Lung Cancer; September 9-12, 2023. Singapore. Abstract OA12.05