Durvalumab Receives FDA Approval for Treatment of Non-Small Cell Lung Cancer

Durvalumab (Imfinzi; AstratZeneca) in combination with chemotherapy has been approved by the FDA for the treatment of adult patients with resectable early (IIA-IIIB) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. The decision is based on positive data from the phase 3 AEGEAN trial (NCT03800134), which demonstrated a significant reduction is risk of disease recurrence, progression events, or death.¹

The data showed that patients receiving durvalumab had a significantly longer progression-free survival (PFS) compared with the placebo group. Image Credit: © Tada Images - stock.adobe.com

NSCLC is the most common type of lung cancer, making up approximately 85% of all cases and accounts for 1-fifth of all cancer deaths amongst men and women. Standard of care treatment typically includes a combination of radiation therapy, chemotherapy, targeted therapy, and immunotherapy, which is typically recommended for patients with stage 4 NSCLC. The development of immunotherapies has resulted in significant advancements for NSCLC, as well as other cancers. Monoclonal antibodies, bispecifics, and combination therapies have demonstrated clinical success in treating disease and prolonging patients’ lives.²

Durvalumab is a human monoclonal that binds to PD-L1 and blocks the interaction between PD-L1 with PD-1 and CD80, thereby interrupting tumor immune-evading tactics. It has multiple indications in combination therapies for treatment of other diseases such as small cell lung cancer, biliary tract cancer, or unresectable hepatocellular carcinoma. In the AEGEAN trial results, published in the New England Journal of Medicine, demonstrated clinically meaningful results, leading to its approval for the treatment of NSCLC.³

The randomized, double-blind, multi-center, placebo-controlled phase 3 trial involved 802 patients who were assigned to receive durvalumab plus platinum-based chemotherapy (400 patients) or placebo (402 patients) administered intravenously every 3 weeks for 4 cycles before surgery, followed by adjuvant durvalumab or placebo intravenously every 4 weeks for 12 cycles. The primary end points of the study were event-free survival (defined as the time to the earliest occurrence of progressive disease that precluded surgery or prevented completion of surgery, disease recurrence, or death from any cause) and pathological complete response (CR) (evaluated centrally).⁴

The data showed that patients receiving durvalumab had a significantly longer progression-free survival (PFS) compared with the placebo group, with a 0.68 stratified hazard ratio for disease recurrence, progression or death (95% confidence interval [CI], 0.53 to 0.88; P=.004). At 12 months, event-free survival was observed in 73.4% of patients in the durvalumab group (95% CI, 67.9 to 78.1) and 64.5% of patients in the placebo group (95% CI, 58.8 to 69.6).⁴

When assessing pathological CR, durvalumab was associated with greater responses than placebo (17.2% vs. 4.3% at the final analysis; difference, 13.0 percentage points; 95% CI, 8.7 to 17.6; P<.001 at interim analysis of data from 402 patients). These benefits were observed regardless of NSCLC stage and PD-L1 expression. Adverse events were a maximum of grade 3 or 4 in 42.4% of patients receiving durvalumab compared with 43.2% with placebo.⁴

“This approval brings an important new treatment option that should become a backbone combination approach for patients with resectable non-small cell lung cancer, who have historically faced high rates of recurrence even after chemotherapy and surgery,” John V. Heymach, MD, PhD, professor and chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, said in a press release. “When added both before and after surgery, durvalumab delivered a significant and meaningful improvement in outcomes in this curative-intent setting.”³

REFERENCES

1. A study of neoadjuvant/adjuvant durvalumab for the treatment of patients with resectable non-small cell lung cancer (aegean). Clinicaltrials.gov identifier: NCT03800134. Updated May 23, 2024. Accessed August 16, 2024. https://clinicaltrials.gov/study/NCT03800134
2. Non-small cell lung cancer. Yale Medicine. Accessed August 16, 2024. https://www.yalemedicine.org/conditions/non-small-cell-lung-cancer
3. Imfinzi® (durvalumab) approved in the US for the treatment of resectable non-small cell lung cancer before and after surgery. AstraZeneca. August 16, 2024. Accessed August 16, 2024. https://www.astrazeneca-us.com/media/press-releases/2024/imfinzir-durvalumab-approved-in-the-us-for-the-treatment-of-resectable-non-small-cell-lung-cancer-before-and-after-surgery.html#
4. Heymach J, Harpole D, Mitsudomi T, et al. Perioperative durvalumab for resectable non-small cell lung cancer. N Engl J Med. October 23, 2023. Accessed August 16, 2024. doi: 10.1056/NEJMoa2304875