さまよう薬剤師のブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist. Another face is an investor.

Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial.

9月からJournal Club再開です。

プレゼンターは、呼吸器内科医です。 2016年 Lancet Oncolに発表された、BRAFV600E変異陽性のstageNSCLC患者に対する、dabrafenibtrametinib2剤併用のphase 2.

 


Abstract

 

BACKGROUND:

 

Activating BRAF(V600E) (Val600Glu) mutations are found in about 1-2% of lung adenocarcinomas, which might provide an opportunity for targeted treatment in these patients. Dabrafenib is an oral selective inhibitor of BRAF kinase. We did a trial to assess the clinical activity of dabrafenib in patients with advanced non-small-cell lung cancer (NSCLC) positive for the BRAF(V600E) mutation.

 

METHODS:

 

In this phase 2, multicentre, non-randomised, open-label study, we enrolled previously treated and untreated patients with stage IV metastatic BRAF(V600E)-positive NSCLC. Patients received oral dabrafenib 150 mg twice daily. The primary endpoint was investigator-assessed overall response, which was assessed in patients who had received at least one dose of dabrafenib; safety was also assessed in this population. The study is ongoing but not enrolling patients in this cohort. This trial is registered with ClinicalTrials.gov, number NCT01336634.

 

FINDINGS:

 

Between Aug 3, 2011, and Feb 25, 2014, 84 patients were enrolled, six of whom had not previously received systemic treatment for NSCLC. 26 of the 78 previously treated patients achieved an investigator-assessed overall response (33% [95% CI 23-45]). Four of the six previously untreated patients had an objective response. One patient died from an intracranial haemorrhage that was judged by the investigator to be due to the study drug. Serious adverse events were reported in 35 (42%) of 84 patients. The most frequent grade 3 or worse adverse events were cutaneous squamous-cell carcinoma in ten (12%), asthenia in four (5%), and basal-cell carcinoma in four (5%).

 

INTERPRETATION:

 

Dabrafenib showed clinical activity in BRAF(V600E)-positive NSCLC. Our findings suggest that dabrafenib could represent a treatment option for a population of patients with limited therapeutic options.

 

FUNDING:

GlaxoSmithKline.

 

 

感想

 

 

BRAF (V600E) -positive NSCLC について、初めて知りました。

 

本試験 → Cohort B : 前治療ある患者へのdabrafenibtrametinibの併用

Cohort A : 前治療ある患者へのdabrafenib単剤.  

Cohort C : 前治療のない患者へのdabrafenibtrametinibの併用. 報告まち

 

limitationにありましたが、6000名中59名がエントリーということで、RCTは困難ですね。

 

副作用は、楽観視できない結果かなっと感じました。