Phase 2 Study of Dabrafenib Plus Trametinib in Patients With BRAF V600E-Mutant Metastatic NSCLC

被引：105

作者：

Planchard, David ^{[1
]}

Besse, Benjamin ^{[1
]}

Groen, Harry J. M. ^{[2
,3
]}

Hashemi, Sayed M. S. ^{[4
]}

Mazieres, Julien ^{[5
]}

Kim, Tae Min ^{[6
]}

Quoix, Elisabeth ^{[7
]}

Souquet, Pierre-Jean ^{[8
]}

Barlesi, Fabrice ^{[1
,9
]}

Baik, Christina ^{[10
]}

Villaruz, Liza C. ^{[11
]}

Kelly, Ronan J. ^{[12
]}

Zhang, Shirong ^{[13
]}

Tan, Monique ^{[13
]}

Gasal, Eduard ^{[13
]}

Santarpia, Libero ^{[14
]}

Johnson, Bruce E. ^{[15
]}

机构：

[1] Gustave Roussy, Dept Med Oncol, Villejuif, France

[2] Univ Groningen, Dept Pulm Dis, Groningen, Netherlands

[3] Univ Med Ctr Groningen, Groningen, Netherlands

[4] Vrije Univ Amsterdam, Canc Ctr Amsterdam, Dept Pulm Med, Amsterdam UMC, Amsterdam, Netherlands

[5] Hosp Larrey, Thorac Oncol Dept, Toulouse, France

[6] Seoul Natl Univ Hosp, Dept Internal Med, Seoul, South Korea

[7] Univ Hosp Strasbourg, Dept Chest Dis, Strasbourg, France

[8] Hop Jour, Dept Pneumonol & Thorac Oncol, Pierre Benite, France

[9] Aix Marseille Univ, Ctr Rech Cancerol Marseille CRCM, CNRS, INSERM, Marseille, France

[10] Fred Hutchinson Canc Res Ctr, Dept Med, 1124 Columbia St, Seattle, WA 98104 USA

[11] UPMC Hillman Canc Ctr, Div Hematol Oncol, Pittsburgh, PA USA

[12] Baylor Univ, Med Ctr, Charles Sammons Canc Ctr, Dallas, TX USA

[13] Novartis Pharmaceut, E Hanover, NJ USA

[14] Novartis Pharma AG, Basel, Switzerland

[15] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

来源：

JOURNAL OF THORACIC ONCOLOGY | 2022年 / 17卷 / 01期

关键词：

BRAF V600E; Dabrafenib; Genomic analysis; Non-small cell lung cancer; Trametinib; CELL LUNG-CANCER; OPEN-LABEL; COMBINATION THERAPY; 1ST-LINE TREATMENT; MULTICENTER; MELANOMA; CHEMOTHERAPY; MUTATIONS; CRIZOTINIB; RESISTANCE;

D O I：

10.1016/j.jtho.2021.08.011

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: Dabrafenib plus trametinib was found to have robust antitumor activity in patients with BRAF V600Emutant metastatic NSCLC (mNSCLC). We report updated survival analysis of a phase 2 study (NCT01336634) with a minimum of 5-year follow-up and updated genomic data. Methods: Pretreated (cohort B) and treatment-naive (cohort C) patients with BRAF V600E-mutant mNSCLC received dabrafenib 150 mg twice daily and trametinib 2 mg once daily. The primary end point was investigator-assessed overall response rate per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points were duration of response, progression-free survival, overall survival, and safety. Results: At data cutoff, for cohorts B (57 patients) and C (36 patients), the median follow-up was 16.6 (range: 0.5- 78.5) and 16.3 (range: 0.4-80) months, overall response rate (95% confidence interval [CI]) was 68.4% (54.8-80.1) and 63.9% (46.2-79.2), median progression-free survival (95% CI) was 10.2 (6.9-16.7) and 10.8 (7.0-14.5) months, and median overall survival (95% CI) was 18.2 (14.3-28.6) and 17.3 (12.3-40.2) months, respectively. The 4-and 5 year survival rates were 26% and 19% in pretreated patients and 34% and 22% in treatment-naive patients, respectively. A total of 17 patients (18%) were still alive. The most frequent adverse event was pyrexia (56%). Exploratory genomic analysis indicated that the presence of coexisting genomic alterations might influence clinical outcomes in these patients; however, these results require further investigation. Conclusions: Dabrafenib plus trametinib therapy was found to have substantial and durable clinical benefit, with a manageable safety profile, in patients with BRAF V600Emutant mNSCLC, regardless of previous treatment. (c) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：103 / 115

页数：13

共 50 条

[1] Efficacy of Dabrafenib Plus Trametinib Combination in Patients with BRAF V600E-Mutant NSCLC in Real World Setting
Auliac, J. B.
Bayle, S.
Do, P.
Legarff, G.
Guisier, F.
Roa, M.
Falchero, L.
Huchon, E.
Quere, G.
Jeannin, G.
Doubre, H.
Baud, M.
Hobeika, J.
Chouaid, C.
[J]. JOURNAL OF THORACIC ONCOLOGY, 2019, 14 (10) : S857 - S857
[2] Encorafenib plus binimetinib for BRAF V600E-mutant metastatic NSCLC: clinical implications of the phase 2 PHAROS study
Ramalingam, Suresh S.
Carlisle, Jennifer W.
[J]. FUTURE ONCOLOGY, 2024,
[3] Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study
Subbiah, V
Kreitman, R. J.
Wainberg, Z. A.
Cho, J. Y.
Schellens, J. H. M.
Soria, J. C.
Wen, P. Y.
Zielinski, C. C.
Cabanillas, M. E.
Boran, A.
Ilankumaran, P.
Burgess, P.
Salas, T. Romero
Keam, B.
[J]. ANNALS OF ONCOLOGY, 2022, 33 (04) : 406 - 415
[4] Efficacy of Dabrafenib Plus Trametinib Combination in Patients with BRAF V600E-Mutant NSCLC in Real-World Setting: GFPC 01-2019
Auliac, Jean-Bernard
Bayle, Sophie
Do, Pascal
Le Garff, Gwenaelle
Roa, Magali
Falchero, Lionel
Huchot, Eric
Quere, Gilles
Jeannin, Gaelle
Metivier, Anne-Cecile
Hobeika, Joelle
Guisier, Florian
Chouaid, Christos
[J]. CANCERS, 2020, 12 (12) : 1 - 8
[5] Safety and Efficacy of Dabrafenib Plus Trametinib in Chinese Patients With BRAF V600E-Mutation Positive Metastatic NSCLC
Fan, Y.
Jianying, Z.
Yuanyuan, Z.
Yan, Y.
Nong, Y.
Juan, L.
Jialei, W.
Jun, Z.
Zhehai, W.
Jun, C.
Zhu, T.
Li, H.
Li, Z.
[J]. JOURNAL OF THORACIC ONCOLOGY, 2022, 17 (09) : S423 - S423
[6] Phase 2 trial (BRF113928) of dabrafenib (D) plus trametinib (T) in patients (pts) with previously untreated BRAF V600E-mutant metastatic non-small cell lung cancer (NSCLC)
Planchard, D.
Smit, E. F.
Groen, H. J. M.
Mazieres, J.
Besse, B.
Helland, A.
Giannone, V.
D'Amelio, A.
Zhang, P.
Mookerjee, B.
Johnson, B.
[J]. ANNALS OF ONCOLOGY, 2017, 28
[7] Dabrafenib Plus Trametinib for BRAF V600E-Mutant Non-small Cell Lung Cancer: A Patient Case Report
Janet Pan
[J]. Clinical Drug Investigation, 2019, 39 : 1003 - 1007
[8] Dabrafenib plus trametinib in BRAF V600E-mutant high-grade (HGG) and low-grade glioma (LGG).
Subbiah, Vivek
Stein, Alexander
van den Bent, Martin
Wick, Antje
de Vos, Filip Y.
von Bubnoff, Nikolas
van Linde, Myra E.
Lai, Albert
Prager, Gerald W.
Campone, Mario
Fasolo, Angelica
Lopez-Martin, Jose A.
Kim, Tae Min
Hofheinz, Ralf-Dieter
Blay, Jean-Yves
Cho, Daniel C.
Gazzah, Anas
Pouessel, Damien
Yachnin, Jeffrey
Boran, Aislyn
Burgess, Paul
Ilankumaran, Palanichamy
Gasal, Eduard
Wen, Patrick Y.
[J]. CANCER RESEARCH, 2021, 81 (13)
[9] Dabrafenib Plus Trametinib for BRAF V600E-Mutant Non-small Cell Lung Cancer: A Patient Case Report
Pan, Janet
[J]. CLINICAL DRUG INVESTIGATION, 2019, 39 (10) : 1003 - 1007
[10] Adverse Event Management in Patients with BRAF V600E-Mutant Non-Small Cell Lung Cancer Treated with Dabrafenib plus Trametinib
Chalmers, Anna
Cannon, Laura
Akerley, Wallace
[J]. ONCOLOGIST, 2019, 24 (07): : 963 - 972

← 1 2 3 4 5 →