Neoadjuvant PD-1 and PD-L1 Blockade With Chemotherapy for Borderline Resectable and Unresectable Stage III Non-Small...

Area of Science:

• Oncology
• Immunotherapy
• Thoracic Surgery

Background:

• Stage III non-small cell lung cancer (NSCLC) with T4 and/or N2-N3 involvement presents limited therapeutic options and poor prognoses.
• Neoadjuvant chemoimmunotherapy has emerged as a promising strategy to enhance resectability and pathological outcomes in these patients.

Purpose of the Study:

• To assess the efficacy of neoadjuvant programmed cell death 1 protein (PD-1) or programmed cell death 1 ligand 1 (PD-L1) blockade combined with chemotherapy.
• To evaluate improvements in surgical outcomes and pathological responses for patients with T4 and/or N2-N3 stage III NSCLC.

Main Methods:

• A multicenter cohort study analyzed data from 112 patients treated between February 2018 and January 2024.
• Patients received neoadjuvant PD-1/PD-L1 inhibitors plus platinum-based chemotherapy at academic and tertiary care centers in the US and Italy.
• Pathological and survival outcomes, including pathological complete response (pCR), major pathological response, and event-free survival (EFS), were assessed.

Main Results:

• 84% of patients underwent surgical resection, with a pCR rate of 29% and a major pathological response rate of 42.2%.
• Patients with PD-L1 expression ≥50% and high tumor mutational burden showed the highest pCR rate (44.4%).
• Event-free survival was significantly longer in patients achieving pCR (not reached vs. 27.8 months).

Conclusions:

• Neoadjuvant PD-1/PD-L1 blockade plus chemotherapy demonstrates high pathological response rates and surgical resectability in advanced NSCLC.
• This combination therapy represents a viable treatment option for borderline resectable or unresectable stage III NSCLC.
• Further validation through prospective studies is warranted to confirm these findings.