Durvalumab-Based Treatment Before and After Surgery Improves EFS in Early-Stage NSCLC

Durvalumab (Imfinzi) plus neoadjuvant chemotherapy followed by surgery and adjuvant single-agent durvalumab significantly improved event-free survival (EFS) vs neoadjuvant chemotherapy and surgery alone in patients with resectable stage IIA-IIIB non–small cell lung cancer (NSCLC), according to data from the phase 3 AEGEAN trial (NCT03800134).¹

Findings from final pathologic complete response (pCR) and major pathologic response (MPR) analyses proved to be consistent with a previous press release issued in June 2022.² Moreover, no new safety signals were observed in the neoadjuvant or adjuvant settings. The toxicity profile of durvalumab in combination with neoadjuvant chemotherapy proved to be consistent with what is already known about this regimen. The addition of durvalumab did not result in increased complications or toxicities vs chemotherapy alone, nor did it negatively affect patients’ ability to undergo surgery.

“Treating patients early with durvalumab both before and after surgery delivers a significant and clinically meaningful benefit in resectable NSCLC, where new options are urgently needed to offer patients the best chance of long-term survival,” John V. Heymach, MD, PhD, professor and chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, stated in a press release. “The AEGEAN results provide compelling evidence that this novel durvalumab regimen can drive improved outcomes in this curative-intent setting.”

The double-blind, placebo-controlled, multicenter trial enrolled patients with newly diagnosed and previously untreated histologically or cytologically confirmed NSCLC who had resectable disease.³ Patients were required to be at least 18 years of age, have an ECOG performance status of 0 or 1, acceptable organ and bone marrow function, known PD-L1 status, and planned surgery.

Those who had a history of allogeneic organ transplantation, active or previously documented autoimmune disorders, a history of another primary malignancy or active primary immunodeficiency, active infection, brain metastases, or who received preoperative radiation as part of their care plan, were excluded.

A total of 802 participants were randomly assigned 1:1 to receive durvalumab at a fixed dose of 1500 mg plus chemotherapy or placebo plus chemotherapy every 3 weeks for 4 cycles before undergoing surgery, followed by durvalumab or placebo given every 4 weeks for up to 12 cycles post surgery.¹

Stratification factors included disease stage and PD-L1 expression levels.⁴ Tumor assessments are planned for the time that neoadjuvant treatment was completed before surgery, every 12 weeks for the first year, every 24 weeks for 2 to 4 years, and then on an annual basis thereafter.

The primary end points of the trial were pCR and EFS. Secondary end points comprise MPR, disease-free survival (DFS), overall survival (OS), safety, and quality of life.

Investigators conducted the final pCR analyses after all patients had the opportunity for surgery. Pathology assessment was done in accordance with the trial protocol.

More detailed data will be shared at a future medical conference and shared with global health authorities. Investigators will continue to evaluate important secondary end points such as DFS and OS.

“Patients with resectable NSCLC face unacceptably high rates of recurrence, despite treatment with chemotherapy and surgery. We have shown that adding [durvalumab] before and after surgery significantly increased the time patients live without recurrence or progressive events. We will continue to follow patients for OS.”

References

1. Imfinzi significantly improved event-free survival in AEGEAN phase III trial for patients with resectable non-small cell lung cancer. News release. AstraZeneca. March 9, 2023. Accessed March 9, 2023. https://www.astrazeneca.com/media-centre/press-releases/
2. Imfinzi plus chemotherapy significantly improved pathologic complete response in AEGEAN phase III trial in resectable non-small cell lung cancer. News release. AstraZeneca. June 30, 2022. Accessed March 9, 2023. https://www.astrazeneca.com/media-centre/press-releases/
3. A study of neoadjuvant/adjuvant durvalumab for the treatment of patients with resectable non-small cell lung cancer (AEGEAN). Clinicaltrials.gov. Updated November 21, 2022. Accessed March 9, 2023. https://www.clinicaltrials.gov/ct2/show/NCT03800134
4. Heymach J, Taube J, Mitsudomi T, et al. P1. 18-02 The AEGEAN phase 3 trial of neoadjuvant/adjuvant durvalumab in patients with resectable stage II/III NSCLC. J Thorac Oncol. 2019;14(10):S625-S626. doi:10.1016/j.jtho.2019.08.1318