Efficacy and Safety of BRAF Inhibitors With or Without MEK Inhibitors in BRAF-Mutant Advanced Non–Small-Cell Lung Cancer: Findings From a Real-Life Cohort
Real-life comparative data on BRAF inhibitors (BRAFi) and BRAFi + MEK inhibitors (MEKi) combination in BRAF-mutant (BRAFm) non–small-cell lung cancer (NSCLC) is lacking. Consecutive BRAFm advanced NSCLC patients (n = 58) treated in 9 Israeli centers in 2009-2018 were identified. These were divided a...
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| Veröffentlicht in: | Clinical lung cancer 2019-07, Vol.20 (4), p.278-286.e1 |
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| creator | Dudnik, Elizabeth Bar, Jair Peled, Nir Bshara, Elias Kuznetsov, Teodor Cohen, Aharon Yonathan Shochat, Tzippy Nechushtan, Hovav Onn, Amir Agbarya, Abed Moskovitz, Mor Keren, Shoshana Popovits-Hadar, Noa Urban, Damien Mishaeli, Moshe Rabinovich, Natalie Maimon Brenner, Ronen Zer, Alona Rotem, Ofer Roisman, Laila C. Wollner, Mira |
| description | Real-life comparative data on BRAF inhibitors (BRAFi) and BRAFi + MEK inhibitors (MEKi) combination in BRAF-mutant (BRAFm) non–small-cell lung cancer (NSCLC) is lacking.
Consecutive BRAFm advanced NSCLC patients (n = 58) treated in 9 Israeli centers in 2009-2018 were identified. These were divided according to mutation subtype and treatment into groups A1 (V600E, BRAFi; n = 5), A2 (V600E, BRAFi + MEKi; n = 15), A3 (V600E, no BRAFi; n = 7), B1 (non-V600E, BRAFi ± MEKi; n = 7), and B2 (non-V600E, no BRAFi; n = 23); one patient received both BRAFi and BRAFi + MEKi. Safety, objective response rate, progression-free survival with BRAFi ± MEKi, and overall survival were assessed.
Objective response rate was 40%, 67%, and 33% in groups A1, A2, and B1, respectively (P = .5 for comparison between groups A1 and A2). In group B1, G469A and L597R mutations were associated with response to BRAFi + MEKi. Median progression-free survival was 1.2 months (95% confidence interval [CI], 0.5-5.3), 5.5 months (95% CI, 0.7-9.3), and 3.6 months (95% CI, 1.5-6.7) for groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .04). Median overall survival with BRAFi ± MEKi was 1.7 months (95% CI, 0.5-NR), 9.5 months (95% CI, 0.2-14.9), and 7.1 months (95% CI, 1.8-NR) in groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .6). Safety profiles differed slightly, and similar treatment discontinuation rates were observed with BRAFi and BRAFi + MEKi.
In the real-life setting, activity and safety of BRAFi + MEKi in V600E BRAFm NSCLC are comparable to those observed in prospective clinical trials; the combination of BRAFi + MEKi is superior to monotherapy with a BRAFi. Further research should be done to explore the impact of BRAFi + MEKi treatment on the natural history of BRAFm NSCLC.
Little is known regarding the performance of BRAF inhibitors (BRAFi) and BRAFi + MEK inhibitor (MEKi) combination in the real-life setting. A real-life cohort of BRAF-mutant (BRAFm) non–small-cell lung cancer (NSCLC) patients (n = 58) was analyzed, focusing on comparative efficacy and safety of BRAFi and BRAFi + MEKi combination. In V600E BRAFm NSCLC, BRAFi + MEKi are effective, well tolerated, and superior to BRAFi. Non–V600E kinase-active BRAFm NSCLC may respond to BRAFi + MEKi. |
| doi_str_mv | 10.1016/j.cllc.2019.03.007 |
| format | Article |
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Consecutive BRAFm advanced NSCLC patients (n = 58) treated in 9 Israeli centers in 2009-2018 were identified. These were divided according to mutation subtype and treatment into groups A1 (V600E, BRAFi; n = 5), A2 (V600E, BRAFi + MEKi; n = 15), A3 (V600E, no BRAFi; n = 7), B1 (non-V600E, BRAFi ± MEKi; n = 7), and B2 (non-V600E, no BRAFi; n = 23); one patient received both BRAFi and BRAFi + MEKi. Safety, objective response rate, progression-free survival with BRAFi ± MEKi, and overall survival were assessed.
Objective response rate was 40%, 67%, and 33% in groups A1, A2, and B1, respectively (P = .5 for comparison between groups A1 and A2). In group B1, G469A and L597R mutations were associated with response to BRAFi + MEKi. Median progression-free survival was 1.2 months (95% confidence interval [CI], 0.5-5.3), 5.5 months (95% CI, 0.7-9.3), and 3.6 months (95% CI, 1.5-6.7) for groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .04). Median overall survival with BRAFi ± MEKi was 1.7 months (95% CI, 0.5-NR), 9.5 months (95% CI, 0.2-14.9), and 7.1 months (95% CI, 1.8-NR) in groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .6). Safety profiles differed slightly, and similar treatment discontinuation rates were observed with BRAFi and BRAFi + MEKi.
In the real-life setting, activity and safety of BRAFi + MEKi in V600E BRAFm NSCLC are comparable to those observed in prospective clinical trials; the combination of BRAFi + MEKi is superior to monotherapy with a BRAFi. Further research should be done to explore the impact of BRAFi + MEKi treatment on the natural history of BRAFm NSCLC.
Little is known regarding the performance of BRAF inhibitors (BRAFi) and BRAFi + MEK inhibitor (MEKi) combination in the real-life setting. A real-life cohort of BRAF-mutant (BRAFm) non–small-cell lung cancer (NSCLC) patients (n = 58) was analyzed, focusing on comparative efficacy and safety of BRAFi and BRAFi + MEKi combination. In V600E BRAFm NSCLC, BRAFi + MEKi are effective, well tolerated, and superior to BRAFi. Non–V600E kinase-active BRAFm NSCLC may respond to BRAFi + MEKi.</description><identifier>ISSN: 1525-7304</identifier><identifier>EISSN: 1938-0690</identifier><identifier>DOI: 10.1016/j.cllc.2019.03.007</identifier><identifier>PMID: 31060855</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - mortality ; Cohort Studies ; Dabrafenib ; Female ; Humans ; Imidazoles - therapeutic use ; Lung cancer ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Lung Neoplasms - mortality ; Male ; MAP Kinase Kinase Kinases - antagonists & inhibitors ; MAP Kinase Kinase Kinases - genetics ; Middle Aged ; Mutation - genetics ; Non-V600E ; Oximes - therapeutic use ; Proto-Oncogene Proteins B-raf - antagonists & inhibitors ; Proto-Oncogene Proteins B-raf - genetics ; Pyridones - therapeutic use ; Pyrimidinones - therapeutic use ; Survival Analysis ; Trametinib ; Vemurafenib ; Vemurafenib - therapeutic use</subject><ispartof>Clinical lung cancer, 2019-07, Vol.20 (4), p.278-286.e1</ispartof><rights>2019 Elsevier Inc.</rights><rights>Copyright © 2019 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-ccf67a9977ba693378ce8579e88048bc6848c35a6e974da2153ab6e6692197d93</citedby><cites>FETCH-LOGICAL-c356t-ccf67a9977ba693378ce8579e88048bc6848c35a6e974da2153ab6e6692197d93</cites><orcidid>0000-0002-9143-751X ; 0000-0001-8455-9327</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1525730419300804$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31060855$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dudnik, Elizabeth</creatorcontrib><creatorcontrib>Bar, Jair</creatorcontrib><creatorcontrib>Peled, Nir</creatorcontrib><creatorcontrib>Bshara, Elias</creatorcontrib><creatorcontrib>Kuznetsov, Teodor</creatorcontrib><creatorcontrib>Cohen, Aharon Yonathan</creatorcontrib><creatorcontrib>Shochat, Tzippy</creatorcontrib><creatorcontrib>Nechushtan, Hovav</creatorcontrib><creatorcontrib>Onn, Amir</creatorcontrib><creatorcontrib>Agbarya, Abed</creatorcontrib><creatorcontrib>Moskovitz, Mor</creatorcontrib><creatorcontrib>Keren, Shoshana</creatorcontrib><creatorcontrib>Popovits-Hadar, Noa</creatorcontrib><creatorcontrib>Urban, Damien</creatorcontrib><creatorcontrib>Mishaeli, Moshe</creatorcontrib><creatorcontrib>Rabinovich, Natalie Maimon</creatorcontrib><creatorcontrib>Brenner, Ronen</creatorcontrib><creatorcontrib>Zer, Alona</creatorcontrib><creatorcontrib>Rotem, Ofer</creatorcontrib><creatorcontrib>Roisman, Laila C.</creatorcontrib><creatorcontrib>Wollner, Mira</creatorcontrib><creatorcontrib>Israel Lung Cancer Group</creatorcontrib><title>Efficacy and Safety of BRAF Inhibitors With or Without MEK Inhibitors in BRAF-Mutant Advanced Non–Small-Cell Lung Cancer: Findings From a Real-Life Cohort</title><title>Clinical lung cancer</title><addtitle>Clin Lung Cancer</addtitle><description>Real-life comparative data on BRAF inhibitors (BRAFi) and BRAFi + MEK inhibitors (MEKi) combination in BRAF-mutant (BRAFm) non–small-cell lung cancer (NSCLC) is lacking.
Consecutive BRAFm advanced NSCLC patients (n = 58) treated in 9 Israeli centers in 2009-2018 were identified. These were divided according to mutation subtype and treatment into groups A1 (V600E, BRAFi; n = 5), A2 (V600E, BRAFi + MEKi; n = 15), A3 (V600E, no BRAFi; n = 7), B1 (non-V600E, BRAFi ± MEKi; n = 7), and B2 (non-V600E, no BRAFi; n = 23); one patient received both BRAFi and BRAFi + MEKi. Safety, objective response rate, progression-free survival with BRAFi ± MEKi, and overall survival were assessed.
Objective response rate was 40%, 67%, and 33% in groups A1, A2, and B1, respectively (P = .5 for comparison between groups A1 and A2). In group B1, G469A and L597R mutations were associated with response to BRAFi + MEKi. Median progression-free survival was 1.2 months (95% confidence interval [CI], 0.5-5.3), 5.5 months (95% CI, 0.7-9.3), and 3.6 months (95% CI, 1.5-6.7) for groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .04). Median overall survival with BRAFi ± MEKi was 1.7 months (95% CI, 0.5-NR), 9.5 months (95% CI, 0.2-14.9), and 7.1 months (95% CI, 1.8-NR) in groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .6). Safety profiles differed slightly, and similar treatment discontinuation rates were observed with BRAFi and BRAFi + MEKi.
In the real-life setting, activity and safety of BRAFi + MEKi in V600E BRAFm NSCLC are comparable to those observed in prospective clinical trials; the combination of BRAFi + MEKi is superior to monotherapy with a BRAFi. Further research should be done to explore the impact of BRAFi + MEKi treatment on the natural history of BRAFm NSCLC.
Little is known regarding the performance of BRAF inhibitors (BRAFi) and BRAFi + MEK inhibitor (MEKi) combination in the real-life setting. A real-life cohort of BRAF-mutant (BRAFm) non–small-cell lung cancer (NSCLC) patients (n = 58) was analyzed, focusing on comparative efficacy and safety of BRAFi and BRAFi + MEKi combination. In V600E BRAFm NSCLC, BRAFi + MEKi are effective, well tolerated, and superior to BRAFi. Non–V600E kinase-active BRAFm NSCLC may respond to BRAFi + MEKi.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - mortality</subject><subject>Cohort Studies</subject><subject>Dabrafenib</subject><subject>Female</subject><subject>Humans</subject><subject>Imidazoles - therapeutic use</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - mortality</subject><subject>Male</subject><subject>MAP Kinase Kinase Kinases - antagonists & inhibitors</subject><subject>MAP Kinase Kinase Kinases - genetics</subject><subject>Middle Aged</subject><subject>Mutation - genetics</subject><subject>Non-V600E</subject><subject>Oximes - therapeutic use</subject><subject>Proto-Oncogene Proteins B-raf - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><subject>Pyridones - therapeutic use</subject><subject>Pyrimidinones - therapeutic use</subject><subject>Survival Analysis</subject><subject>Trametinib</subject><subject>Vemurafenib</subject><subject>Vemurafenib - therapeutic use</subject><issn>1525-7304</issn><issn>1938-0690</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhS0EomXgBVggL9kk-GfiH8RmiGZKxRSkFsTSchyn41FiF9upNDveoVuejich6RTECulK90r3nKNrfwC8xKjECLM3-9L0vSkJwrJEtESIPwKnWFJRICbR42muSFVwipYn4FlKe4QIo5g8BScUI4ZEVZ2Cn-uuc0abA9S-hVe6s_kAQwffX6428NzvXONyiAl-c3kHQ7zvYczwYv3x37Xz947iYszaZ7hqb7U3toWfgv_14-5q0H1f1Lbv4Xb017Cel_Et3DjfOn-d4CaGAWp4aXVfbF1nYR12Iebn4Emn-2RfPPQF-LpZf6k_FNvPZ-f1alsYWrFcGNMxrqXkvNFMUsqFsaLi0gqBlqIxTCzFpNTMSr5sNcEV1Q2zjEmCJW8lXYDXx9ybGL6PNmU1uGSmc7W3YUyKEEowRXSqBSBHqYkhpWg7dRPdoONBYaRmKmqvZipqpqIQVROVyfTqIX9sBtv-tfzBMAneHQV2euWts1El4-z8gy5ak1Ub3P_yfwP_PZ1g</recordid><startdate>201907</startdate><enddate>201907</enddate><creator>Dudnik, Elizabeth</creator><creator>Bar, Jair</creator><creator>Peled, Nir</creator><creator>Bshara, Elias</creator><creator>Kuznetsov, Teodor</creator><creator>Cohen, Aharon Yonathan</creator><creator>Shochat, Tzippy</creator><creator>Nechushtan, Hovav</creator><creator>Onn, Amir</creator><creator>Agbarya, Abed</creator><creator>Moskovitz, Mor</creator><creator>Keren, Shoshana</creator><creator>Popovits-Hadar, Noa</creator><creator>Urban, Damien</creator><creator>Mishaeli, Moshe</creator><creator>Rabinovich, Natalie Maimon</creator><creator>Brenner, Ronen</creator><creator>Zer, Alona</creator><creator>Rotem, Ofer</creator><creator>Roisman, Laila C.</creator><creator>Wollner, Mira</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9143-751X</orcidid><orcidid>https://orcid.org/0000-0001-8455-9327</orcidid></search><sort><creationdate>201907</creationdate><title>Efficacy and Safety of BRAF Inhibitors With or Without MEK Inhibitors in BRAF-Mutant Advanced Non–Small-Cell Lung Cancer: Findings From a Real-Life Cohort</title><author>Dudnik, Elizabeth ; Bar, Jair ; Peled, Nir ; Bshara, Elias ; Kuznetsov, Teodor ; Cohen, Aharon Yonathan ; Shochat, Tzippy ; Nechushtan, Hovav ; Onn, Amir ; Agbarya, Abed ; Moskovitz, Mor ; Keren, Shoshana ; Popovits-Hadar, Noa ; Urban, Damien ; Mishaeli, Moshe ; Rabinovich, Natalie Maimon ; Brenner, Ronen ; Zer, Alona ; Rotem, Ofer ; Roisman, Laila C. ; Wollner, Mira</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-ccf67a9977ba693378ce8579e88048bc6848c35a6e974da2153ab6e6692197d93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - mortality</topic><topic>Cohort Studies</topic><topic>Dabrafenib</topic><topic>Female</topic><topic>Humans</topic><topic>Imidazoles - therapeutic use</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - mortality</topic><topic>Male</topic><topic>MAP Kinase Kinase Kinases - antagonists & inhibitors</topic><topic>MAP Kinase Kinase Kinases - genetics</topic><topic>Middle Aged</topic><topic>Mutation - genetics</topic><topic>Non-V600E</topic><topic>Oximes - therapeutic use</topic><topic>Proto-Oncogene Proteins B-raf - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins B-raf - genetics</topic><topic>Pyridones - therapeutic use</topic><topic>Pyrimidinones - therapeutic use</topic><topic>Survival Analysis</topic><topic>Trametinib</topic><topic>Vemurafenib</topic><topic>Vemurafenib - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dudnik, Elizabeth</creatorcontrib><creatorcontrib>Bar, Jair</creatorcontrib><creatorcontrib>Peled, Nir</creatorcontrib><creatorcontrib>Bshara, Elias</creatorcontrib><creatorcontrib>Kuznetsov, Teodor</creatorcontrib><creatorcontrib>Cohen, Aharon Yonathan</creatorcontrib><creatorcontrib>Shochat, Tzippy</creatorcontrib><creatorcontrib>Nechushtan, Hovav</creatorcontrib><creatorcontrib>Onn, Amir</creatorcontrib><creatorcontrib>Agbarya, Abed</creatorcontrib><creatorcontrib>Moskovitz, Mor</creatorcontrib><creatorcontrib>Keren, Shoshana</creatorcontrib><creatorcontrib>Popovits-Hadar, Noa</creatorcontrib><creatorcontrib>Urban, Damien</creatorcontrib><creatorcontrib>Mishaeli, Moshe</creatorcontrib><creatorcontrib>Rabinovich, Natalie Maimon</creatorcontrib><creatorcontrib>Brenner, Ronen</creatorcontrib><creatorcontrib>Zer, Alona</creatorcontrib><creatorcontrib>Rotem, Ofer</creatorcontrib><creatorcontrib>Roisman, Laila C.</creatorcontrib><creatorcontrib>Wollner, Mira</creatorcontrib><creatorcontrib>Israel Lung Cancer Group</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical lung cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dudnik, Elizabeth</au><au>Bar, Jair</au><au>Peled, Nir</au><au>Bshara, Elias</au><au>Kuznetsov, Teodor</au><au>Cohen, Aharon Yonathan</au><au>Shochat, Tzippy</au><au>Nechushtan, Hovav</au><au>Onn, Amir</au><au>Agbarya, Abed</au><au>Moskovitz, Mor</au><au>Keren, Shoshana</au><au>Popovits-Hadar, Noa</au><au>Urban, Damien</au><au>Mishaeli, Moshe</au><au>Rabinovich, Natalie Maimon</au><au>Brenner, Ronen</au><au>Zer, Alona</au><au>Rotem, Ofer</au><au>Roisman, Laila C.</au><au>Wollner, Mira</au><aucorp>Israel Lung Cancer Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and Safety of BRAF Inhibitors With or Without MEK Inhibitors in BRAF-Mutant Advanced Non–Small-Cell Lung Cancer: Findings From a Real-Life Cohort</atitle><jtitle>Clinical lung cancer</jtitle><addtitle>Clin Lung Cancer</addtitle><date>2019-07</date><risdate>2019</risdate><volume>20</volume><issue>4</issue><spage>278</spage><epage>286.e1</epage><pages>278-286.e1</pages><issn>1525-7304</issn><eissn>1938-0690</eissn><abstract>Real-life comparative data on BRAF inhibitors (BRAFi) and BRAFi + MEK inhibitors (MEKi) combination in BRAF-mutant (BRAFm) non–small-cell lung cancer (NSCLC) is lacking.
Consecutive BRAFm advanced NSCLC patients (n = 58) treated in 9 Israeli centers in 2009-2018 were identified. These were divided according to mutation subtype and treatment into groups A1 (V600E, BRAFi; n = 5), A2 (V600E, BRAFi + MEKi; n = 15), A3 (V600E, no BRAFi; n = 7), B1 (non-V600E, BRAFi ± MEKi; n = 7), and B2 (non-V600E, no BRAFi; n = 23); one patient received both BRAFi and BRAFi + MEKi. Safety, objective response rate, progression-free survival with BRAFi ± MEKi, and overall survival were assessed.
Objective response rate was 40%, 67%, and 33% in groups A1, A2, and B1, respectively (P = .5 for comparison between groups A1 and A2). In group B1, G469A and L597R mutations were associated with response to BRAFi + MEKi. Median progression-free survival was 1.2 months (95% confidence interval [CI], 0.5-5.3), 5.5 months (95% CI, 0.7-9.3), and 3.6 months (95% CI, 1.5-6.7) for groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .04). Median overall survival with BRAFi ± MEKi was 1.7 months (95% CI, 0.5-NR), 9.5 months (95% CI, 0.2-14.9), and 7.1 months (95% CI, 1.8-NR) in groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .6). Safety profiles differed slightly, and similar treatment discontinuation rates were observed with BRAFi and BRAFi + MEKi.
In the real-life setting, activity and safety of BRAFi + MEKi in V600E BRAFm NSCLC are comparable to those observed in prospective clinical trials; the combination of BRAFi + MEKi is superior to monotherapy with a BRAFi. Further research should be done to explore the impact of BRAFi + MEKi treatment on the natural history of BRAFm NSCLC.
Little is known regarding the performance of BRAF inhibitors (BRAFi) and BRAFi + MEK inhibitor (MEKi) combination in the real-life setting. A real-life cohort of BRAF-mutant (BRAFm) non–small-cell lung cancer (NSCLC) patients (n = 58) was analyzed, focusing on comparative efficacy and safety of BRAFi and BRAFi + MEKi combination. In V600E BRAFm NSCLC, BRAFi + MEKi are effective, well tolerated, and superior to BRAFi. Non–V600E kinase-active BRAFm NSCLC may respond to BRAFi + MEKi.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>31060855</pmid><doi>10.1016/j.cllc.2019.03.007</doi><orcidid>https://orcid.org/0000-0002-9143-751X</orcidid><orcidid>https://orcid.org/0000-0001-8455-9327</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1525-7304 |
| ispartof | Clinical lung cancer, 2019-07, Vol.20 (4), p.278-286.e1 |
| issn | 1525-7304 1938-0690 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2232130330 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols - therapeutic use Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - mortality Cohort Studies Dabrafenib Female Humans Imidazoles - therapeutic use Lung cancer Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - mortality Male MAP Kinase Kinase Kinases - antagonists & inhibitors MAP Kinase Kinase Kinases - genetics Middle Aged Mutation - genetics Non-V600E Oximes - therapeutic use Proto-Oncogene Proteins B-raf - antagonists & inhibitors Proto-Oncogene Proteins B-raf - genetics Pyridones - therapeutic use Pyrimidinones - therapeutic use Survival Analysis Trametinib Vemurafenib Vemurafenib - therapeutic use |
| title | Efficacy and Safety of BRAF Inhibitors With or Without MEK Inhibitors in BRAF-Mutant Advanced Non–Small-Cell Lung Cancer: Findings From a Real-Life Cohort |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-18T10%3A19%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Efficacy%20and%20Safety%20of%20BRAF%20Inhibitors%20With%20or%20Without%20MEK%20Inhibitors%20in%20BRAF-Mutant%20Advanced%20Non%E2%80%93Small-Cell%20Lung%20Cancer:%20Findings%20From%20a%20Real-Life%20Cohort&rft.jtitle=Clinical%20lung%20cancer&rft.au=Dudnik,%20Elizabeth&rft.aucorp=Israel%20Lung%20Cancer%20Group&rft.date=2019-07&rft.volume=20&rft.issue=4&rft.spage=278&rft.epage=286.e1&rft.pages=278-286.e1&rft.issn=1525-7304&rft.eissn=1938-0690&rft_id=info:doi/10.1016/j.cllc.2019.03.007&rft_dat=%3Cproquest_cross%3E2232130330%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2232130330&rft_id=info:pmid/31060855&rft_els_id=S1525730419300804&rfr_iscdi=true |