Perioperative durvalumab-based regimen improves outcomes in resectable NSCLC
In individuals with resectable non-small-cell lung cancer (NSCLC), the addition of perioperative durvalumab to neoadjuvant chemotherapy improved pathologic complete response (pCR) and event-free survival (EFS), findings from the AEGEAN study have shown.
“AEGEAN achieved its primary endpoint of pathologic response,” said Dr John Heymach from The University of Texas MD Anderson Cancer Center, Houston, Texas, US, at AACR 2023. This was reflected by the statistically significant increase in pCR (17 percent vs 4 percent; p=0.000036) and major pathologic response with durvalumab vs placebo (33 percent vs 12 percent; p=0.000002).
There was also a significant EFS improvement with durvalumab vs placebo (median not reached vs 25.9 months; stratified hazard ratio [HR], 0.68; p=003902). Median follow-up in censored patients was 11.7 months. At 24 months, EFS rate was higher with durvalumab than with placebo (63 percent vs 52 percent). [AACR 2023, abstract CT005]
Moreover, there was a clear and consistent EFS benefit with durvalumab vs placebo regardless of the planned platinum agent. The respective HRs for cisplatin and carboplatin were 0.59 and 0.73.
The pCR and EFS benefits with durvalumab vs placebo were observed across major subgroups, with a trend towards greater benefit in current smokers (24 percent vs 4 percent [pCR] and HR, 0.48 [EFS]).
Regardless of causality, the durvalumab and placebo arms had similar rates of grade 3/4 adverse events (AEs; 42 percent vs 43 percent) and grade 3/4 AEs possibly related to treatment (32 percent vs 33 percent). Any-grade immune-mediated AE rate was higher with durvalumab vs placebo (24 percent vs 10 percent), but these were largely grade 1/2 events.
The regimen had a manageable safety profile that aligned with the known safety profiles of durvalumab and chemo. The addition of durvalumab did not impact the completion of neoadjuvant chemo or surgery, said Heymach.
An effective backbone
The study comprised 802 treatment-naïve patients (median age 65 years, 72 percent male) with resectable NSCLC (stage IIA–IIIB), confirmed PD-L1 status, and no documented EGFR/ALK aberrations. They were randomized 1:1 to receive platinum-based chemo plus IV durvalumab 1,500 mg or placebo Q3W for four cycles, followed by surgery. They continued with durvalumab or placebo Q4W (up to 12 cycles) postoperatively.
“NSCLC remains a leading cause of cancer mortality, and historically, about half of patients who undergo resection experience recurrence,” noted Heymach in a press release. “Anything we can do to increase cure rates for these patients could potentially be a tremendous advance.”
For early-stage NSCLC, surgery remains the primary treatment with curative intent. For resectable NSCLC, immunotherapy with PD-(L)1 inhibition in the neoadjuvant or adjuvant setting has shown benefit, noted Heymach. “Perioperative regimens combining these two approaches could further provide benefit by priming antitumour immunity when the tumour is still in place and when draining lymph nodes are present, and by providing sustained PD1 pathway inhibition after surgery to potentially eradicate micro-metastases.”
AEGEAN showed that combining perioperative immunotherapy and neoadjuvant chemotherapy is a potential new treatment for resectable NSCLC, Heymach said. “Our study has laid the foundation that we can build on by designing new combination regimens on top of this effective backbone.”
But does AEGEAN define SoC for NSCLC?
“Not yet,” stressed discussant Dr Roy Herbst from the Yale School of Medicine, New Haven, Connecticut, US. “It is ‘a’ standard, but not ‘the’ standard of care (SoC).”
Given the lack of comparison with the current SoC, it is impossible to determine the role of the different components, he said. “More work is needed to better identify and evaluate pathologic biomarkers of response and future therapy. Additional trial maturity is needed to better understand the benefit of extra adjuvant therapy.”
The study is ongoing to evaluate longer term outcomes, including EFS, disease-free survival and overall survival.