Pembrolizumab is currently approved for advanced non-small cell lung cancer (NSCLC) patients with programed death ligand-1 (PD-L1) expression ≥50% as first-line therapy. However, the efficacy or immune-related adverse events (irAEs) are unclear in patients with ultra-high PD-L1 expression.
We retrospectively analyzed patients with advanced NSCLC and PD-L1 tumor proportion score (TPS) of ≥ 50% who received pembrolizumab as first-line therapy at 11 institutions in Japan between February 2017 and January 2018. Patients were separated to TPS 50-74% cohort and TPS ≥75% (ultra-high PD-L1 expression) cohort. Early irAEs were defined as irAEs that occurred within 3 weeks after commencing pembrolizumab therapy.
In total, 161 patients were included; 70 patients in TPS 50-74% cohort and 91 patients in TPS≥75% cohort. The patient characteristics and the frequency of irAEs were not different between both cohorts. The objective response rates (ORR) and disease control rates (DCR) were 54.3% (38/70) and 77.1% (54/70) in TPS 50-74% cohort, 47.3% (43/91) and 69.2% (63/91) in TPS≥75% cohort (P = 0.43, P = 0.29, respectively). Time to treatment failure (TTF) curve showed that TTF of TPS≥75% cohort was comparable to that of TPS 50-74% cohort within 4 months (hazard ratio [HR] = 1.19, 95% confidence interval [CI], 0.74-1.91; P = 0.47). However, TTF of TPS≥75% cohort showed the tendency to be longer in late phase (4 months or later) (HR = 0.48, 95% CI, 0.19-1.25; P = 0.13). In the patients who achieved complete response or partial response, TTF of TPS≥75% cohort was longer than that of TPS 50-74% (HR = 0.49, 95% CI, 0.23-1.03; P = 0.059). The medians of overall survival were not reached in both cohorts. The follow-up is ongoing.
The ORR and DCR of TPS≥75% cohort were comparable to those of TPS 50-74% cohort. However, the patients with ultra-high PD-L1 expression could continue pembrolizumab therapy long when they achieved objective responses.
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