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

Bruce E. Johnson; Christina S. Baik; Julien Mazieres; Harry J.M. Groen; Barbara Melosky; Jürgen Wolf; Fatemeh Asad Zadeh Vosta Kolaei; Wen Hsing Wu; Stefanie Knoll; Meryem Ktiouet Dawson; Adam Johns; David Planchard

doi:10.1016/j.jtocrr.2022.100324

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

Bruce E. Johnson, Christina S. Baik, Julien Mazieres, Harry J.M. Groen, Barbara Melosky, Jürgen Wolf, Fatemeh Asad Zadeh Vosta Kolaei, Wen Hsing Wu, Stefanie Knoll, Meryem Ktiouet Dawson, Adam Johns, David Planchard

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

9 Citations (Scopus)

Résumé

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.

langue originale	Anglais
Numéro d'article	100324
journal	JTO Clinical and Research Reports
Volume	3
Numéro de publication	5
Les DOIs	https://doi.org/10.1016/j.jtocrr.2022.100324
état	Publié - 1 mai 2022

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10.1016/j.jtocrr.2022.100324

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Johnson, B. E., Baik, C. S., Mazieres, J., Groen, H. J. M., Melosky, B., Wolf, J., Zadeh Vosta Kolaei, F. A., Wu, W. H., Knoll, S., Ktiouet Dawson, M., Johns, A., & Planchard, D. (2022). Clinical Outcomes With Dabrafenib Plus Trametinib in a Clinical Trial Versus Real-World Standard of Care in Patients With BRAF-Mutated Advanced NSCLC. JTO Clinical and Research Reports, 3(5), Article 100324. https://doi.org/10.1016/j.jtocrr.2022.100324

@article{8035006d75db46ab958562a55cd99d71,

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

abstract = "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.",

keywords = "BRAF inhibitor, BRAF-mutated aNSCLC, Immune-checkpoint inhibitors, Indirect comparison, MEK inhibitor, Platinum-based chemotherapy",

author = "Johnson, {Bruce E.} and Baik, {Christina S.} and Julien Mazieres and Groen, {Harry J.M.} and Barbara Melosky and J{\"u}rgen Wolf and {Zadeh Vosta Kolaei}, {Fatemeh Asad} and Wu, {Wen Hsing} and Stefanie Knoll and {Ktiouet Dawson}, Meryem and Adam Johns and David Planchard",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = may,

day = "1",

doi = "10.1016/j.jtocrr.2022.100324",

language = "English",

volume = "3",

journal = "JTO Clinical and Research Reports",

issn = "2666-3643",

number = "5",

}

Johnson, BE, Baik, CS, Mazieres, J, Groen, HJM, Melosky, B, Wolf, J, Zadeh Vosta Kolaei, FA, Wu, WH, Knoll, S, Ktiouet Dawson, M, Johns, A & Planchard, D 2022, 'Clinical Outcomes With Dabrafenib Plus Trametinib in a Clinical Trial Versus Real-World Standard of Care in Patients With BRAF-Mutated Advanced NSCLC', JTO Clinical and Research Reports, VOL. 3, Numéro 5, 100324. https://doi.org/10.1016/j.jtocrr.2022.100324

Clinical Outcomes With Dabrafenib Plus Trametinib in a Clinical Trial Versus Real-World Standard of Care in Patients With BRAF-Mutated Advanced NSCLC. / Johnson, Bruce E.; Baik, Christina S.; Mazieres, Julien et al.
Dans: JTO Clinical and Research Reports, Vol 3, Numéro 5, 100324, 01.05.2022.

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

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

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

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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

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ER -