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

Dudnik, Elizabeth; Bar, Jair; Peled, Nir; Bshara, Elias; Kuznetsov, Teodor; Cohen, Aharon Y.; Shochat, Tzippy; Nechushtan, Hovav; Onn, Amir; Agbarya, Abed; Moskovitz, Mor; Keren, S.; Popovits-Hadar, Noa; Urban, Damien; Mishaeli, Moshe; Rabinovich, Natalie Maimon; Brenner, Ronen; Zer, Alona; Rotem, Ofer; Roisman, Laila C.; Wollner, Mira

doi:10.1016/j.cllc.2019.03.007

Cited by 13 publications

(5 citation statements)

References 14 publications

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“…Serious adverse events (grade 3-4) occurred in 69% and 56% of patients, respectively, including pyrexia (11-16%), hypertension (11%) and elevated liver enzymes (11%). Results from these studies have been subsequently confirmed in a real-world setting [180]. Clinical trials currently underway are investigating the efficacy of other BRAF and MEK inhibitors, for example encorafenib and binimetinib (NCT03915951).…”

Section: Dabrafenib and Trametinibmentioning

confidence: 86%

Targeted Therapy in Advanced and Metastatic Non-Small Cell Lung Cancer. An Update on Treatment of the Most Important Actionable Oncogenic Driver Alterations

König

Prince

Rothschild

2021

Cancers

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Due to groundbreaking developments and continuous progress, the treatment of advanced and metastatic non-small cell lung cancer (NSCLC) has become an exciting, but increasingly challenging task. This applies, in particular, to the subgroup of NSCLC with oncogenic driver alterations. While the treatment of epidermal growth factor receptor (EGFR)-mutated and anaplastic lymphoma kinase (ALK)-rearranged NSCLC with various tyrosine kinase inhibitors (TKIs) is well-established, new targets have been identified in the last few years and new TKIs introduced in clinical practice. Even for KRAS mutations, considered for a long time as an “un-targetable” alteration, promising new drugs are emerging. The detection and in-depth molecular analysis of resistance mechanisms has further fueled the development of new therapeutic strategies. The objective of this review is to give a comprehensive overview on the current landscape of targetable oncogenic alterations in NSCLC.

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Section: Dabrafenib and Trametinibmentioning

confidence: 86%

Targeted Therapy in Advanced and Metastatic Non-Small Cell Lung Cancer. An Update on Treatment of the Most Important Actionable Oncogenic Driver Alterations

König

Prince

Rothschild

2021

Cancers

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“…Patients with BRAF mutations often exhibit high PD-L1 expression rates and high TMB [51]. Retrospective studies suggest moderate clinical benefits of single-agent ICIs in non-selective PD-L1 patients with BRAF-mutated NSCLC [55][56][57][58]. Emerging evidence suggests that different oncogenic drivers have different effects on tumor immune microenvironment, which may lead to the different clinical benefits of ICIs.…”

Section: Level Of Evidence: Moderate Strength Of Recommendation: Mode...mentioning

confidence: 99%

Uncommon/rare oncogenic drivers in non‐small cell lung cancer: Consensus and contention

Wu,

Lu,

Cheng

et al. 2023

Medicine Advances

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The importance of uncommon/rare oncogenic drivers in non‐small cell lung cancer (NSCLC) was underscored during the 20th China Lung Cancer Summit. These drivers, while present in a significant proportion of NSCLC patients, remain a challenge for diagnosis and therapeutic targeting. In the never‐smokers/low smokers category with mutations such as EGFR and HER2, the efficacy of immune checkpoint inhibitors (ICIs) remains suboptimal, attributed to lower PD‐L1 expression and tumor mutation burden (TMB). However, heavy smokers, often with mutations like KRAS, may derive benefits from ICIs, as supported by trials like CheckMate‐057. With the complex landscape of these drivers and their clinical implications, the summit culminated in six pivotal consensus points, aiming to guide future research and clinical decisions. Despite the advancements, the detection, interpretation, and therapeutic strategies involving these drivers necessitate further exploration and standardization.

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“…BRAF inhibitor therapy alone has little effect as monotherapy 121 , 124 . However, the BRAF inhibitor (dabrafenib) plus MEK1 and 2 inhibitor (trametinib) demonstrate good activity in phase II clinical trials with an ORR of 63% and mDoR of 9 to 15 months 125 – 127 . The BRAF inhibitor vemurafenib demonstrates activity among those with BRAF -V600E mutations exhibiting ORR between 37–44% and mPFS of 6.5 months 128 , 129 .…”

Section: Braf Mutationsmentioning

confidence: 99%

Targeted therapies in non-small cell lung cancer: present and future

McLaughlin,

Berkman,

Nana-Sinkam

2023

Fac Rev

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Lung cancer is the leading cause of malignancy-related death in the United States and the second most common cancer diagnosis worldwide. In the last two decades, lung cancer treatment has evolved to include advances in the development of mutation-based targeting, immunotherapy, radiation therapy, and minimally invasive surgical techniques. The discovery of lung cancer as a molecularly heterogeneous disease has driven investigation into the development of targeted therapies resulting in improved patient outcomes. Despite these advances, there remain opportunities, through further investigation of mechanisms of resistance, to develop novel therapeutics that better direct the personalization of lung cancer therapy. In this review, we highlight developments in the evolution of targeted therapies in non-small cell lung cancer, as well as future directions shaped by emerging patterns of resistance.

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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

Cited by 13 publications

References 14 publications

Targeted Therapy in Advanced and Metastatic Non-Small Cell Lung Cancer. An Update on Treatment of the Most Important Actionable Oncogenic Driver Alterations

Targeted Therapy in Advanced and Metastatic Non-Small Cell Lung Cancer. An Update on Treatment of the Most Important Actionable Oncogenic Driver Alterations

Uncommon/rare oncogenic drivers in non‐small cell lung cancer: Consensus and contention

Targeted therapies in non-small cell lung cancer: present and future

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