Investigation of Durvalumab in Lung Cancer Treatment

Advancements in Non-Small-Cell Lung Cancer Treatment

Recent scientific advancements have expanded treatment options for patients diagnosed with advanced non-small-cell lung cancer (NSCLC). Notable among these are targeted therapies aimed at specific mutations in the EGFR tyrosine kinase and anaplastic lymphoma kinase (ALK). These mutations affect cell signaling pathways, which can lead to cancer development. Patients with these mutations possess an EGFR+/ALK+ status, while those without exhibit an EGFR-/ALK- status.

Additionally, the protein molecule PD-L1 has emerged as a significant target for assessing treatment efficacy. Tumor cells express PD-L1 to evade the immune response, and durvalumab—a monoclonal antibody—works by inhibiting PD-L1 activity, thereby enhancing the immune system’s ability to identify and eliminate tumor cells.

The ATLANTIC Study Overview

The ATLANTIC study, published in The Lancet Oncology, explored the effects of durvalumab on advanced NSCLC patients with varying EGFR/ALK statuses and PD-L1 tumor expression levels. Conducted by researchers in South Korea, the study included data from global centers across Asia, Europe, and North America.

To qualify for the study, participants had to show disease progression or recurrence after receiving at least two different treatment regimens. Patients diagnosed with mixed NSCLC, those with prior exposure to anti-PD-L1 drugs, or individuals with immune diseases were excluded. Ultimately, 444 patients were enrolled in the study, divided into three separate groups based on their mutation and PD-L1 expression status:

– **EGFR+/ALK+ patients with 25% or less PD-L1 expression** (111 patients)
– **EGFR-/ALK- patients with 25% or less PD-L1 expression** (265 patients)
– **EGFR-/ALK- patients with at least 90% PD-L1 expression** (68 patients)

All participants received an intravenous infusion of durvalumab at a dose of 10 mg/kg every two weeks, continuing until disease progression, intolerable toxicity, or a maximum treatment duration of twelve months.

Study Assessments and Outcomes

Researchers conducted regular assessments, including clinical evaluations, laboratory tests, tumor assessments, and monitoring for adverse effects throughout the duration of the study. The primary focus was on determining the confirmed objective response to durvalumab treatment, while secondary outcomes encompassed overall survival, progression-free survival, disease control, duration of response, and time to response.

Findings on Durvalumab’s Efficacy

The results indicated that patients in the first group (EGFR+/ALK+) had a lower response rate compared to those classified as EGFR-/ALK-. However, the presence of PD-L1 significantly enhanced the response to durvalumab across both EGFR and ALK statuses. Notably, patients with at least 25% PD-L1 tumor expression experienced higher objective response rates and improved overall survival.

A sustained response was observed in patients across all three groups, irrespective of their PD-L1 expression status. Furthermore, durvalumab exhibited an acceptable tolerability profile, with most adverse events being non-severe and manageable. Consequently, the rate of treatment discontinuation due to adverse events was relatively low.

Comparative Analysis with Other Treatments

Durvalumab’s efficacy is comparable to other immune-targeting antibody therapies previously studied in NSCLC, such as nivolumab and pembrolizumab. The ATLANTIC study contributes to the growing evidence supporting the effectiveness of immune checkpoint inhibitors in treating this form of lung cancer, highlighting durvalumab’s clinical activity and potential advantages for patients with elevated PD-L1 tumor expression.

Future Directions for Research

Further clinical studies are necessary to delve deeper into durvalumab’s efficacy and activity among specific subpopulations of NSCLC patients based on their EGFR/ALK statuses.

Author Information

Written by Maggie Leung, PharmD

Reference

Garassino, M. C., Cho, B., Kim, J., Mazières, J., Vansteenkiste, J., Lena, H., . . . Szalai, Z. (2018). Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): An open-label, single-arm, phase 2 study. The Lancet Oncology, 19(4), 521-536. doi:10.1016/s1470-2045(18)30144-x