Thoracic Oncology Research Updates

Review of systemic therapy integration in early-stage resectable non–small cell lung cancer notes FDA approvals of adjuvant osimertinib for EGFR-mutant and alectinib for ALK-rearranged pathologic stage II–III disease, and summarizes evidence supporting chemoimmunotherapy in adjuvant, neoadjuvant, and perioperative settings for clinical/pathologic stage IB–III disease. The authors highlight remaining equipoise about whether adjuvant or neoadjuvant/perioperative chemoimmunotherapy is preferable and whether patients with pathologic complete response after neoadjuvant immunotherapy benefit from further adjuvant immunotherapy, and cite ongoing randomized trials addressing these questions.

In a single-arm phase II trial of 31 patients with metastatic NSCLC and low or negative tumor PD-L1 who had progressed on prior anti-PD-1 therapy, ipilimumab plus nivolumab combined with subablative radiotherapy produced objective response rates of 7% at 6 weeks and 10% at 12 weeks (best response 29%) and disease control rates of 58% and 39% at 6 and 12 weeks. Median overall survival differed by best response (3.1 months for progressive disease, 13.5 months for stable disease, 22.5 months for partial/complete response), all patients experienced treatment-related adverse events (grade 3 in 26%) with immune-related AEs leading to discontinuation in 16%, and early peripheral T-cell activation was more pronounced in responders.

In a single-arm phase II study of 30 patients with resectable stage IIIA–IIIB NSCLC treated with three cycles of neoadjuvant camrelizumab plus chemotherapy (27 undergoing resection), pathological complete response occurred in 33.3% and major pathological response in 50.0%, with a 2-year disease-free survival rate of 77.4% at median 27.2 months follow-up and grade ≥3 treatment-related adverse events in 13.3%. Exploratory analyses found that higher baseline CD8+ and CD8+ naïve-like T cells in blood and tumor, closer spatial proximity of CD8+ naïve-like T cells to tumor cells, and higher circulating CCL3 were associated with pCR and improved DFS, while post-neoadjuvant ctDNA positivity predicted shorter DFS and longitudinal ctDNA detected relapse earlier than radiography.