TY - JOUR
T1 - Clinical Outcomes With Dabrafenib Plus Trametinib in a Clinical Trial Versus Real-World Standard of Care in Patients With BRAF-Mutated Advanced NSCLC
AU - Johnson, Bruce E.
AU - Baik, Christina S.
AU - Mazieres, Julien
AU - Groen, Harry J.M.
AU - Melosky, Barbara
AU - Wolf, Jürgen
AU - Zadeh Vosta Kolaei, Fatemeh Asad
AU - Wu, Wen Hsing
AU - Knoll, Stefanie
AU - Ktiouet Dawson, Meryem
AU - Johns, Adam
AU - Planchard, David
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Introduction: BRAF mutations are rare in patients with NSCLC, and treatment options are limited. Dabrafenib plus trametinib (dab-tram) was approved for BRAFV600-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.
AB - Introduction: BRAF mutations are rare in patients with NSCLC, and treatment options are limited. Dabrafenib plus trametinib (dab-tram) was approved for BRAFV600-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.
KW - BRAF inhibitor
KW - BRAF-mutated aNSCLC
KW - Immune-checkpoint inhibitors
KW - Indirect comparison
KW - MEK inhibitor
KW - Platinum-based chemotherapy
UR - http://www.scopus.com/inward/record.url?scp=85130174079&partnerID=8YFLogxK
U2 - 10.1016/j.jtocrr.2022.100324
DO - 10.1016/j.jtocrr.2022.100324
M3 - Article
AN - SCOPUS:85130174079
SN - 2666-3643
VL - 3
JO - JTO Clinical and Research Reports
JF - JTO Clinical and Research Reports
IS - 5
M1 - 100324
ER -