Correlation between PD-L1 expression and T790M status is unclear. Therapeutic interventions could affect PD-L1 expression, and rebiopsied fresh samples may be desirable to analyze PD-L1 expression.
We retrospectively analyzed PD-L1 expression and T790M status in rebiopsied samples of EGFR-mutant NSCLC after acquired resistance. PD-L1 immunohistochemistry was performed using the SP142 anti-PD-L1 antibody for tumor cell membrane staining. H-score was adopted to evaluate both percentage and intensity, and scores ≥1 were defined as PD-L1 + , and scores ≥10 as strong PD-L1+. T790M status was examined using the PNA-LNA PCR clamp or cycleave method. Survival analyses were done according to PD-L1 and T790M status at first rebiopsy.
We investigated 63 available rebiopsied histologic samples in 45 patients. Median H-score in T790M+ (n = 25) samples was 0 (range, 0-6), whereas T790M- (n = 38) was 1 (range, 0-91) (Wilcoxon, p = 0.0451). PD-L1+ was confirmed in 12 (48%) of 25 T790M+ samples, and in 28 (74%) of 38 T790M- (p = 0.0383). Strong PD-L1+ was identified in 0 (0%) T790M + , but in 3 (8%) T790M- (p = 0.1500). Ten patients received multiple rebiopsies. In 7 of these 10 patients, T790M status had changed from T790M+ to T790M-. Among 4 of these 7, PD-L1 expression also changed from PD-L1- to PD-L1 + , in accordance with T790M status from T790M+ to T790M-. Median overall survival (OS) of PD-L1+ (n = 30) vs. PD-L1- (n = 15) were 55.0 months vs. not reached months, respectively (p = 0.1071). Median OS of T790M+ (n = 16) vs. T790M- (n = 29) were 80.3 vs. 55.0 months, respectively (p = 0.1340).
T790M+ status was correlated to lower PD-L1 expression. Conversely, T790M- status was associated with higher PD-L1 expression, suggesting a potential efficacy of anti-PD-1/PD-L1 immunotherapies for T790M- population. PD-L1 expression might have a prognostic value, even in EGFR-mutant NSCLC.
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A. Hata: Akito Hata received lecture fee from Chugai, Astra Zeneca, Boehringer Ingelheim, and Eli Lilly. All other authors have declared no conflicts of interest.