Long-term outcomes of neoadjuvant immunochemotherapy in paT ients with resectable non-small cell lung cancer: experience of the N.N. Blokhin National Medical Research Center of Oncology (towards a new standard in national clinical practice)

Purpose: To assess the long-term outcomes of neoadjuvant chemoimmunotherapy in patients with resectable non-small cell lung cancer (NSCLC).

Materials and methods: This analysis included 60 patients with NSCLC (stages IB–IIIB, TNM 8) who underwent multimodal treatment between 2019 and 2023 at the N.N. Blokhin National Medical Research Center of Oncology. The neoadjuvant regimen consisted of three cycles of combination therapy with pembrolizumab (200 mg) plus platinum-based chemotherapy, administered every 21 days per investigator’s choice. Following neoadjuvant therapy, all patients underwent radical surgical resection. Event-free survival (EFS) was evaluated, defined as the time from the first administration of therapy to disease progression confirmed by radiological assessment, clinical progression, or death from any cause. The impact of baseline clinical and morphological characteristics, as well as the achievement of complete and major pathological responses, on long-term treatment outcomes was analyzed.

Results: With a median follow-up of 29 months (95% CI, 25-32), the 2-year EFS rate for all included patients (n=60) was 79.6%. Statistically significant differences in survival were observed based on tumor mutational status (p=0.0006) and smoking status (p=0.0336). The median EFS was not reached in the group of patients without driver mutations and was 17 months (95% CI 6-22) in the group with activating mutations (p=0.0006). The 2-year EFS rates were 85.7% and 33.3%, respectively. In the group of patients with a positive smoking status, the 2-year EFS was 85.1%, compared to 58.3% in never-smokers. Achieving a major pathological response (MPR) significantly correlated with higher EFS rates (p=0.0016). The estimated 2-year EFS was 93.4% in the subgroup of patients who achieved MPR, compared to 58.3% in those without a significant pathological response. A trend toward better outcomes was observed in the group of patients who achieved complete pathological response (p=0.063), with 2-year EFS rates of 95.4% and 68.3%, respectively.

Conclusion: Neoadjuvant chemoimmunotherapy has demonstrated significant long-term efficacy in patients with resectable non-small cell lung cancer, supporting its potential integration as a novel standard of care, particularly in patients without driver mutations and with a positive smoking history. Achieving a major pathological response is associated with a more favorable prognosis. The role of other factors requires further investigation, including the identification of potential candidates for adjuvant therapy.