Neoadjuvant vs perioperative chemo-immunotherapy according to pathological response in resectable non-small cell lung cancer: a reconstructed individual patient data meta-analysis

Neoadjuvant chemo-immunotherapy transformed early stage non-small cell lung cancer (NSCLC) treatment. However, the prognostic value of different pathological responses and the impact of adjuvant immunotherapy within a chemotherapy-immunotherapy perioperative strategy remains unclear. We estimated time-to-event outcomes by graphical reconstruction of event-free survival curves by pathological response (major pathological response, no major pathological response) reported in early stage NSCLC neoadjuvant or perioperative chemotherapy-immunotherapy trials. The major pathological response 1%-10% subgroup, previously unreported, was retrieved by removing patients achieving pathological response from the major pathological response group. Survival analysis by pathological response and comparison between neoadjuvant or perioperative strategies within subgroups were assessed. A statistically significant event-free survival difference according to pathological response was found, showing a prognostic gradient shifting from pathological response (good), major pathological response 1%-10% (intermediate), and no major pathological response (poor). There was no difference between neoadjuvant or perioperative strategies within subgroups; however, a trend for event-free survival benefit with perioperative and neoadjuvant chemotherapy-immunotherapy was observed in major pathological response 1%-10% and no major pathological response patients, respectively. In conclusion, a pathological response-based algorithm could better tailor early stage NSCLC treatment.