PD-L1 expression + EGFR mutation

EGFR gene mutations at exon 19 or 21 are seen in lung adenocarcinoma cases. PD-L1 expression was observed in EGFR mutated tissues. Our results should be further validated with large sample size and multicenter clinical data before extrapolation to design immunotherapy strategies.

While cisplatin-based adjuvant chemotherapy has been the standard of care for the past two decades, the recent introduction of immunotherapy has heralded an important milestone in the adjuvant landscape of early-stage non-small cell lung cancer (NSCLC)...Although both atezolizumab and pembrolizumab demonstrated a significant DFS benefit in the intention-to-treat population, key subgroup analyses have raised questions about the role of predictive biomarkers such as PD-L1 expression and EGFR-mutation status. In this review, we examine the data from the two important trials (IMpower010 and PEARLS/KEYNOTE-091), discuss the controversies surrounding adjuvant immunotherapy including appropriate endpoints, biomarker selection and highlight key considerations in oncogene-driven NSCLC. Finally, we propose future directions including the impact of neoadjuvant therapy on developments in the adjuvant immunotherapy paradigm and role of minimal residual disease (MRD).

PD-L1 high expression was associated with poor DFS in completely resected NSCLCs with EGFR mutation, especially in those treated with adjuvant targeted therapy. Figure1. Our study (A) depicted the association between PD-L1 expression (B) or PD-L1 high expression (C, D) and DFS in the completely resected EGFR mutation NSCLC patients.

These results suggested that PD-L1 expression is not an independent risk factor for survival of patients with NSCLC. Because of mutual complementarities of PD-L1 expression and EGFR mutation in NSCLC, both should be simultaneously detected for the patients to achieve eligible treatments.

Additionally, the combination of deep learning features with clinical features demonstrated great stratification capabilities in the prognostic model. Our team would continue to explore the application of imaging markers for treatment selection of lung cancer patients.

The high PD-L1 (≥ 50%) expression was negatively associated with Ex21. These findings may help identify NSCLC patients with an increased risk of postoperative recurrence.

According to the Chinese Expert Consensus on Standards of PD-L1 immunohistochemistry testing for NSCLC, we tested the PD-L1 expression in NSCLC and then the dominant population of anti-PD-1/PD-L1 treatment was screened out. Patients with EGFR mutation were also detected and EGFR mutation was negatively correlated with the expression of PD-1 and PD-L1 as well. On the basis of PD-L1 expression and EGFR mutation status, it may benefit NSCLC patients from individualized treatment. Meanwhile, patients who were under the age of 65, adenocarcinoma, well-differentiated and moderately-differentiated, hypo expression of PD-L1 have a relatively good prognosis, to provide reference for the prognosis evaluation of NSCLC.

B3GNT3 is associated with poor prognosis in lung adenocarcinoma patients. Collectively, these findings may offer new insight into enhancing immune therapy efficacy for lung adenocarcinoma patients.

The common grades 1-2 adverse events were fatigue 10/22 (45.5%), decreased appetite 9/22 (40.9%), hypertension 10/22 (45.5%); the common grades 3-4 adverse events were hypertension 2/22 (9.1%) and mouth ulceration 2/22 (9.1%). Anlotinib combined with PD-1 mAb showed promising efficacy in third-line or further-line treatment of NSCLC, and its adverse effects is tolerable.