A recent meta-analysis has shed light on the role of PD-L1 expression in predicting outcomes for patients with resectable non-small cell lung cancer (NSCLC) undergoing neoadjuvant immunochemotherapy. The study, a comprehensive review of randomized controlled trials (RCTs), suggests that while neoadjuvant immunochemotherapy improves pathological complete response (pCR) and event-free survival (EFS) regardless of PD-L1 expression, overall survival (OS) benefits may be limited to patients with PD-L1 positive tumors.
The research team conducted a meta-analysis of RCTs to evaluate the correlation between PD-L1 expression and its prognostic value in patients with NSCLC receiving preoperative neoadjuvant immunochemotherapy. Their findings indicated that neoadjuvant immunochemotherapy resulted in better pCR and EFS compared to neoadjuvant chemotherapy alone, irrespective of PD-L1 expression levels. However, in terms of OS, a significant benefit was observed only in patients with PD-L1 positive tumors, while PD-L1 negative patients did not experience improved OS.
PD-L1 as a Predictive Biomarker
The study's results align with findings from trials in metastatic NSCLC, such as KEYNOTE-189 and IMpower150, where immunotherapy combined with chemotherapy demonstrated synergistic effects, particularly in patients with high PD-L1 expression. These trials showed improved OS and progression-free survival (PFS) with the combination therapy, with a trend towards longer median OS in patients with higher PD-L1 expression.
Considerations for PD-L1 Testing
Another critical aspect highlighted in the study is the variability of PD-L1 expression in different tumor sites. Evidence suggests that PD-L1 expression can differ between primary lung lesions and metastatic sites, impacting its predictive value. For instance, PD-L1 expression tends to be high in adrenal, liver, and lymph node metastases but low in bone and brain metastases. The researchers emphasize the importance of selecting appropriate tumor specimens for PD-L1 detection in clinical practice, recommending the use of tissue specimens with high prognostic value, such as lung rather than bone specimens.
Limitations and Future Directions
The authors acknowledge several limitations in their meta-analysis. These include the exclusion of grey literature and ongoing clinical trials, the relatively small number of included RCTs, and the limited data on OS in PD-L1 subgroups. Additionally, the analysis included a predominance of PD-1 antibodies compared to PD-L1 antibodies, preventing in-depth analysis of prognostic value variations among different immune checkpoint inhibitor types. The immaturity of OS data also necessitates further investigations with longer follow-up periods.
Clinical Implications
Despite these limitations, the study underscores the potential of PD-L1 as a valuable biomarker for predicting outcomes in NSCLC patients undergoing neoadjuvant immunochemotherapy. The findings support the use of PD-L1 detection in clinical practice to better predict patient outcomes and guide treatment decisions. However, the researchers caution that the OS results are currently inconclusive due to immature data, and further in-depth research is warranted.
