Clinical Outcomes With Dabrafenib Plus Trametinib in a Clinical Trial Versus Real-World Standard of Care in Patients With BRAF-Mutated Advanced NSCLC

INTRODUCTION: BRAF mutations are rare in patients with NSCLC, and treatment options are limited. Dabrafenib plus trametinib (dab-tram) was approved for BRAF(V600)-mutated advanced NSCLC (aNSCLC), based on results from a phase 2 study (NCT01336634). This retrospective analysis compared the effectiveness of dab-tram, based on previously reported clinical trial data, versus real-world standard of care in patients with BRAF-mutated aNSCLC. METHODS: Real-world cohorts were derived from a deidentified real-world database (2011–2020) and included patients with BRAF-mutated aNSCLC receiving first-line platinum-based chemotherapy (PBC), first-line immune checkpoint inhibitors (ICIs) plus PBC, or second-line ICIs. Weighting by odds was used to estimate the average treatment effect of the treated. RESULTS: For first-line dab-tram versus PBC, the hazard ratio (HR; 95% confidence interval) for death in unweighted and weighted analyses was 0.65 (0.39–1.1) and 0.51 (0.29–0.92; p = 0.03), respectively; unweighted and weighted median overall survival was 17.3 (12.3–40.2) versus 14.5 (9.2–19.6) months and 17.3 (14.6-not reached) versus 9.7 (6.4–19.6) months, respectively. Hazard ratio of death in unweighted and weighted analyses was 0.56 (0.29–1.1) and 0.57 (0.28–1.17), respectively, with first-line dab-tram versus PBC plus ICI, and 0.65 (0.39–1.07) and not reported (Cox proportional-hazards assumption violated), respectively, with second-line dab-tram versus ICI. CONCLUSIONS: In this indirect comparison in patients with BRAF-mutated aNSCLC, the risk of death was lower and median overall survival was longer with first-line dab-tram versus PBC. In analyses of dab-tram versus first-line PBC plus ICI or second-line ICI, sample sizes were small and findings were inconclusive with overlapping confidence intervals. Despite some limitations, the study provides useful data for this rare patient population

Comparison of the intranasal and intraperitoneal injection of MPTP on density of dark neurons in pars compacta of substantia nigra in animal model of Parkinson\'s disease

Background and Objective: Parkinson disease (PD) is the second most common neurologic disorder that results following degeneration of dopaminergic neurons in the pars compacta of substintia nigra (SNc). The 1-methyl-1,2,3,6-tetrahydropiridine (MPTP) is a chemical neurotoxin that widely used in animal models of PD. This study was carried out to evaluate the numerical density of dark neurons (DNs) in the SNc in mice subjected to intraperitoneal and intranasal injection of different doses of MPTP. Methods: In this experimental study, 90 male adult BALB/c mice were randomly allocated into four experimental groups including: group 1 (MPTP was injected via i.p. at the dose of 20mg/kg per 2 hours for 4 times), group 2 (MPTP was injected via i.p. at the dose of 30mg/kg for 5 consecutive days), group 3 (MPTP was injected via i.n. at a single dose of 1mg/kg), group 4 (MPTP was injected via i.n. at a single dose of 1mg/kg), four sham and one normal groups. 20 days after the final injection, the animal's brain were removed and stained by toluidine blue. Numerical density of DNs was counted. Results: Intranasal injection of MPTP significantly increased density of dark neurons in the pars compacta of substintia nigra in compare to intraperitoneally injection of MPTP (P<0.05). Conclusion: Intranasal injection of MPTP is more effective manner to induce degeneration of neurons in substintia nigra in animal model of Parkinson's disease

Clinical Outcomes With Dabrafenib Plus Trametinib in a Clinical Trial Versus Real-World Standard of Care in Patients With BRAF-Mutated Advanced NSCLC

Introduction: BRAF mutations are rare in patients with NSCLC, and treatment options are limited. Dabrafenib plus trametinib (dab-tram) was approved for BRAF V600-mutated advanced NSCLC (aNSCLC), based on results from a phase 2 study (NCT01336634). This retrospective analysis compared the effectiveness of dab-tram, based on previously reported clinical trial data, versus real-world standard of care in patients with BRAF-mutated aNSCLC. Methods: Real-world cohorts were derived from a deidentified real-world database (2011-2020) and included patients with BRAF-mutated aNSCLC receiving first-line platinum-based chemotherapy (PBC), first-line immune checkpoint inhibitors (ICIs) plus PBC, or second-line ICIs. Weighting by odds was used to estimate the average treatment effect of the treated. Results: For first-line dab-tram versus PBC, the hazard ratio (HR; 95% confidence interval) for death in unweighted and weighted analyses was 0.65 (0.39-1.1) and 0.51 (0.29-0.92; p = 0.03), respectively; unweighted and weighted median overall survival was 17.3 (12.3-40.2) versus 14.5 (9.2-19.6) months and 17.3 (14.6-not reached) versus 9.7 (6.4-19.6) months, respectively. Hazard ratio of death in unweighted and weighted analyses was 0.56 (0.29-1.1) and 0.57 (0.28-1.17), respectively, with first-line dab-tram versus PBC plus ICI, and 0.65 (0.39-1.07) and not reported (Cox proportional-hazards assumption violated), respectively, with second-line dab-tram versus ICI. Conclusions: In this indirect comparison in patients with BRAF-mutated aNSCLC, the risk of death was lower and median overall survival was longer with first-line dab-tram versus PBC. In analyses of dab-tram versus first-line PBC plus ICI or second-line ICI, sample sizes were small and findings were inconclusive with overlapping confidence intervals. Despite some limitations, the study provides useful data for this rare patient population