Comparison of the treatment results in patients with inoperable non-small cell lung cancer in clinical trials and in standard clinical practice using the pseudorandomization method

Abstract

Rationale: Non-small cell lung cancer (NSCLC) is an aggressive disease with median survival of 1214 months in inoperable patients in the pre-immunotherapy era. Nowadays, under treatment with checkpoint inhibitors median survival is 1922 months. However, only a proportion of patients are sensitive to immune therapy. In this regard, inclusion into clinical trials remains a priority option for patients from medical perspective. Aim: To compare the results in NSCLC patients treated in accordance with the current clinical guidelines and in international clinical trials using the propensity score matching. Materials and methods: The study included data from 344 patients with histologically verified unresectable advanced NSCLC without activating mutations, who received the 1st line systemic medical therapy at various combinations (single agent chemotherapy, platinum doublet-based therapy, chemoimmunotherapy, single agent immunotherapy) within the compulsory health insurance (CHI), and from 90 patients, who received therapy in clinical trials. A direct comparison of long-term treatment results was carried out with the log-rank method. To exclude any influence of individual factors on survival rates, an univariate regression analysis and pseudorandomization accounting for these factors were carried out. Results: The direct comparison of the treatment results showed a higher progression-free survival rate in the patients treated according to clinical trial protocols, than in those treated under CHI (13.3 [95% confidence interval (CI) 8.118.5] months vs 6.4 [95% CI 5.96.9] months). Pseudorandomization of patients based on a combination of statistically significant parameters from the CHI and clinical trial groups showed a significantly longer time to progression in the trial group (13.3 [95% CI 8.318.3] vs 6.3 [95% CI 4.87.7] months). Conclusion: Participation in clinical trials is per se a factor that can significantly impact the longer duration of the treatment effect. This indicates the necessity of the most active use of this tool in clinical practice.