Response to dabrafenib plus trametinib on a rare BRAF mutation (V600_W604 deletion-insertion R) in an advanced non-small cell lung cancer patient.

Although dabrafenib plus trametinib has been approved for BRAF V600E mutation positive advanced non-small cell lung cancer (NSCLC), data on its efficacy against uncommon BRAF mutations are still limited due to their rare frequency. We report a case of 70-year-old woman with BRAF V600_W604 deletion-insertion R-positive stage IVA lung adenocarcinoma, who was successfully treated with dabrafenib plus trametinib. Herein, we discuss the oncogenic role of uncommon BRAF mutations and highlight the importance of performing comprehensive genomic profiling on patients without any targetable gene alterations in companion diagnostics.

Early change in the clearance of pembrolizumab reflects the survival and therapeutic response: A population pharmacokinetic analysis in real-world non-small cell lung cancer patients.

OBJECTIVES: The dosing pattern of pembrolizumab is based on population pharmacokinetic (Pop-PK) analysis of clinical trials. Data for Japanese patients or patient populations with poor conditions such as cachexia are scarce. In this study, we performed a Pop-PK analysis of Japanese non-small cell lung cancer patients and analyzed the relationship between exposure, treatment effect, and survival. MATERIALS AND METHODS: A total of 270 blood samples from 76 patients who received 200 mg pembrolizumab every 3 weeks between March 2017 and December 2018 were included. Blood concentrations of pembrolizumab were measured using mass spectrometry, and Pop-PK analysis was conducted using the Phoenix NLME software with a one-compartment model. RESULTS: The estimated median of clearance (CL) in this analysis population was 0.104 L/day, about half of the historical data for Western data. Overall, pembrolizumab CL decreased over time, with some populations showing increased CL early in the treatment and others showing decreased CL over time. When the time-varying CL was stratified by quartile, the group with decreasing CL showed significantly better treatment response and survival than the group with increasing CL, even though the group included more patients with cachexia. Detailed analysis suggested that the patient population that responded to pembrolizumab treatment had an improved general condition and reduced protein catabolism, further decreasing CL. CONCLUSION: In populations that benefit from pembrolizumab treatment, CL may be reduced early in their treatment, which may be a predictive and prognostic factor. However, further prospective validation of our findings is needed.

Clinical outcomes of pembrolizumab therapy in advanced-NSCLC patients with poor performance status (≥3) and high PD-L1 expression (TPS ≥50%): A case series.

Pembrolizumab is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1) expression tumor proportion score (TPS) ≥50%. The benefit of pembrolizumab in patients with advanced NSCLC and poor performance status (PS ≥3) is limited, even when the tumor is PD-L1-expression-positive. We retrospectively reviewed a total of four NSCLC cases with high PD-L1 expression (TPS ≥50%) and poor PS. The only patient with very high PD-L1 expression (TPS 100%) responded to pembrolizumab, but none of the three patients with high PD-L1 expression (50%-80%) responded to pembrolizumab. In conclusion, pembrolizumab can serve as a treatment option for patients with poor PS, if PD-L1 expression TPS is 100%.