*January 2019* Lung Cancer. This small study from Taiwan was performed to investigate the relationship between PD-L1 expression levels and resistance to EGFR-TKI medications in patients with treatment-naïve advanced EGFR mutant lung adenocarcinoma. (By treatment naïve, these patients had not received any other treatments first such as conventional chemo. By advanced, it meant these patients were all stage III or stage IV.)  Over five years, patients were enrolled that displayed resistance to such therapies along with control group patients who had stable disease or partial responses. A total of 123 patients were included, 66 in the resistant group. Patients with T790M and Exon 20 insertions were excluded. Patients in the study included those that had been treated with gefitinib (Iressa), erlotinib (Tarceva), or afatanib (Gilotrif).

In the present world of lung cancer treatment in patients who do not show benefit from tyrosine kinase inhibitors (TKIs), one of the other treatment options is immunotherapy with checkpoint inhibitors (ie Opdivo, Keytruda). However, frequently if the patient does not benefit from one TKI inhibitor, he may be placed on another first. The authors noted that current studies show that EGFR-mutated non-small cell lung cancer patients exhibited a low response to PD-L1 checkpoint blockade, and therefore the immune checkpoint inhibitors do not improve overall survival. PD-L1 expression level has been stated to be a predictive biomarker regarding the effectiveness of these immune checkpoint inhibitors.

Patients with primary resistance generally had a higher PD-L1 score than those without resistance in the study. Such resistance and these higher scores was associated with lower progression-free survival and overall survival. This study showed that PD-L1 is a predictor for primary resistance to EGFR-TKI treatment. The authors concluded that patients with a higher PD-L1 expression and a higher frequency of primary resistance to EGFR-TKI treatment, should receive new non-TKI treatments without hesitation. It is noted that analysis showed approximately 21% of patients with primary resistance to TKI medicines in the study had PD-L1 levels over 50% which are the levels thought to be associated with better efficacy from immune checkpoint inhibitors. Another 16% had levels of over 25%.

This study has potential for real world application with further investigation. PD-L1 scores, based upon the data shown in the study, could potentially be used in the future to help determine treatment options for EFGR patients. For example, it is possible that somebody that does not appear to be responding to an EGFR-TKI medication and who is shown to have a high PD-L1 score would not benefit from trying other TKI medications and should just be switched to a different type of treatment sooner rather than later. Since such patients with high PD-L1 scores are often the ones who would benefit from immunotherapy more, perhaps immunotherapy could be considered for treatment sooner than at present in patients who do not appear to be responding to TKI’s as initial treatment.

Read more about this study.