Perioperative therapy for better efficacy

Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non-small cell lung cancer (NSCLC). It has now been observed that perioperative therapies can combine the benefits of both treatment options to further improve long-term outcomes.

(red) Lung cancer is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for more than 80% of cases [1–3]. Approximately 25-30% of patients with NSCLC have resectable disease, a proportion that is expected to increase with the increasing use of lung cancer screening programs [4–6]. Surgery remains the primary curative treatment for appropriate patients with early-stage NSCLC. However, many patients experience tumor recurrence within 5 years of surgery, a factor that increases the likelihood of disease-related death [8–12]. Chemotherapy administered in the neoadjuvant or adjuvant phase improves the 5-year survival rate by only a modest 5% compared to surgery alone. The need for effective, long-term measures is therefore high.

The first step in the right direction was the approval of programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors as part of neoadjuvant treatment (in combination with platinum-based chemotherapy) or adjuvant treatment (after resection and platinum-based chemotherapy) for patients with resectable NSCLC [13–18]. Recent melanoma and NSCLC studies now suggest that perioperative therapies that combine the benefits of neoadjuvant and adjuvant immunotherapy could further improve long-term outcomes [19–21]. They activate antitumor immunity while the primary tumor and lymph nodes are still present and eliminate residual micrometastases both before and after surgery.

Focus on perioperative treatment

For this treatment management, durvalumab (^Imfinzi®) has now been approved by Swissmedic for the first-line treatment of adult patients with resectable non-small cell lung cancer (rNSCLC) without known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, regardless of PD-L1 status, in an accelerated procedure for temporary authorization [22]. Durvalumab is a selective human IgG1 monoclonal antibody with high affinity that inhibits the interaction of PD-L1 with PD-1 and CD80 by binding to PD-L1. The approval is based on the results of the planned interim analysis of the placebo-controlled Phase III AEGEAN study [23]. The international, double-blind, placebo-controlled phase III trial investigated the use of the monoclonal antibody perioperatively (i.e. as neoadjuvant and adjuvant therapy) together with neoadjuvant chemotherapy in patients with resectable NSCLC. In the study, 802 patients were randomized to receive a fixed dose of 1500 mg durvalumab plus chemotherapy or placebo plus chemotherapy every three weeks for four cycles prior to surgery, followed by durvalumab or placebo every four weeks (for up to 12 cycles) after surgery.

It was shown that the duration of event-free survival in the serum group was significantly longer than with placebo. At the 12-month milestone analysis, event-free survival was observed in 73.4% of patients receiving durvalumab compared to 64.5% of patients receiving placebo. The incidence of pathologic complete response was significantly higher with durvalumab than placebo (17.2% versus 4.3% in the final analysis). The benefits in event-free survival and pathologic complete response were also observed regardless of stage and PD-L1 expression. Adverse events of grade 3 or 4 or less occurred in 42.4% of patients on durvalumab and 43.2% on placebo. New safety signals were not detected. This approval marks the first perioperative treatment regimen approved in Switzerland and is also AstraZeneca’s first AEGEAN regimen approval worldwide, introducing a new therapeutic option in a curative context for patients with rNSCLC.

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