A Single-Arm, Open-Label, Phase Ib Clinical Study Evaluating the Efficacy and Safety of Durvalumab in Combination with Albumin-Bound Paclitaxel and Carboplatin as Neoadjuvant Therapy for Resectable Stage III Non-Small Cell Lung Cancer.

Abstract

Objective: This study aimed to explore the clinical efficacy and safety of durvalumab combined with albumin-bound paclitaxel and carboplatin as neoadjuvant therapy for resectable stage III Non-small Cell Lung Cancer (NSCLC).

Methods: A single-arm open-label phase Ib study was conducted. A total of 40 patients with driver gene-negative resectable stage III NSCLC were enrolled. All patients received neoadjuvant treatment with durvalumab in combination with albumin-bound paclitaxel and carboplatin. The clinical efficacy, Major Pathological Response (MPR), Complete Pathological Response (pCR), and safety were assessed. Flow cytometry was used to detect the expression of programmed cell death receptor 1 (PD-1) on total T, helper T, and cytotoxic T lymphocytes in peripheral blood before and after neoadjuvant treatment. Adverse reactions during the treatment were recorded. Disease- free Survival (DFS) and Overall Survival (OS) curves were constructed.

Results: After the neoadjuvant treatment, the overall Objective Response Rate (ORR) in the 40 patients with NSCLC was 65.00%. MPR was achieved in 27 patients (67.50%), and pCR was achieved in nine patients (22.50%). The expression levels of PD-1 on total T, helper T, and cytotoxic T lymphocytes in patients with NSCLC significantly decreased after treatment (all p < 0.05). The most common adverse events were hair loss (47.50%), nausea and vomiting (42.50%), and fatigue (40.00%). The majority of adverse events were grades 1 and 2, with a small number of events being grades 3 and 4. At the end of the follow-up period, the average DFS was 21.49 ± 0.99 months, and the average OS was 24.79 ± 0.53 months.

Conclusion: Neoadjuvant treatment with durvalumab combined with albumin-bound paclitaxel and carboplatin as first-line therapy for driver gene-negative stage III NSCLC achieved a high pathological response rate and improved immune function. It is expected to extend patient survival with good tolerability.