Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2024 Apr;15(11):929-933.
doi: 10.1111/1759-7714.15254. Epub 2024 Mar 1.

Exceptionally long-lasting response to dabrafenib plus trametinib treatment in a patient with lung adenocarcinoma harboring the BRAF V600E mutation with high expression of PD-L1: A case report

Takako Inoue  1 , Kei Kunimasa  1 , Motohiro Tamiya  1 , Takahisa Kawamura  1 , Toshiyuki Minami  2   3 , Kazumi Nishino  1
Affiliations
Case Reports

Exceptionally long-lasting response to dabrafenib plus trametinib treatment in a patient with lung adenocarcinoma harboring the BRAF V600E mutation with high expression of PD-L1: A case report

Takako Inoue et al. Thorac Cancer. 2024 Apr.

Abstract

We present a patient with lung adenocarcinoma showing high PD-L1 expression and BRAF V600E mutation, who achieved a remarkable long-term response to the combination therapy of dabrafenib and trametinib (DT treatment) after disease progression on immunotherapy. This case may provide an opportunity for clinicians to consider the order of administration of immunotherapy and molecular targeted therapy for BRAF V600E-positive lung cancer.

Keywords: BRAF V600E; case report; dabrafenib plus trametinib; immunotherapy; non‐small cell lung cancer.

PubMed Disclaimer

Conflict of interest statement

The authors declare the following financial interests/personal relationships that may be considered as potential competing interests. Dr Inoue reports honoraria for lecture fees from AstraZeneca, Ono, MSD, and Chugai. Dr Kunimasa reports honoraria for lecture fees from AstraZeneca, Chugai Pharma, and Novartis. Dr Tamiya reports receiving grants from Boehringer Ingelheim, Ono, MSD, Eisai, Daiichi Sankyo, Chugai, and Janssen; and personal fees from Boehringer Ingelheim, Ono, MSD, Chugai, AstraZeneca, Taiho, Eli Lilly, Novartis, Asahi Kasei, Bristol‐Myers Squibb, Bayer, Amgen, Kyowa‐Kirin, and Nippon Kayaku. Dr Nishino reports receiving grants from Ono, TAIHO, MSD, AbbVie, DAIICHI SANKYO, Amgen, Eisai, Sanofi, Janssen, Novartis, Pfizer, Eli Lilly, Merck, Takeda, Chugai, and Merus; and personal fees from AstraZeneca, Chugai, Nippon Boehringer Ingerheim, Eli Lilly, Roche, Novartis, Pfizer, Merck, Janssen, Bristol Myers Squibb, and Nippon Kayaku. The remaining authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Clinical course. After initiating pembrolizumab therapy, the enlargement of lymph nodes from the neck to mediastinum and the right pleural effusion worsened rapidly. However, after 3 weeks, there was a trend of gradual improvement and the treatment was continued as the findings were assessed as pseudo‐progression. After 3 months, the right pleural effusion exacerbated and the subclavian and axillary lymph nodes re‐enlarged. Dabrafenib and trametinib (DT treatment) was administered as a second‐line therapy. One week after the initiation of dabrafenib‐trametinib (DT) therapy, axillary and subclavian lymphadenopathy alleviated. After 3 weeks, the increase in pleural effusion stopped.
FIGURE 2
FIGURE 2
(a) Lymph nodes at the time of lung cancer diagnosis. In peripheral blood, tumor cells with irregularly sized nuclei and acidophilic cytoplasm were scattered in small clusters or as individual cells. The membranes and some cytoplasm of the tumor cells were highly positive for programmed death‐ligand 1 (PD‐L1) (clone 22C3; Dako) (TPS ≥50%). The cytoplasm of the tumor cells was diffusely positive for BRAF (clone V600E; Roche). The surrounding inflammatory cells were diffusely positive for PD‐L1. CD8‐positive lymphocytes were observed bordering the tumor cells, although they were scarce. (b) Pleural lesions after immunotherapy. The pleura showed reactive hyperplasia, was coated with stratified mesothelial cells, and had marked inflammatory cell infiltration consisting mainly of numerous foamy macrophages and lymphocytes. The ratio of CD4‐positive to CD8‐positive lymphocytes was 10:7, representing a relative increase from that before treatment. Histomorphologically, residual tumor cells were difficult to identify, with only 3–4 cells weakly positive for BRAF and some degenerating tumor cells present in solitary sections. PD‐L1 (22C3) could not be determined because of the paucity of the tumor cells. (c) Cervical lymph nodes enlarged after immunotherapy. Tumor cells that were polymorphous with hyperchromicities, ubiquitous nuclei, and weakly acidophilic cytoplasm were found to have infiltrated in an irregular focal, tissue‐destructive manner, with fibrous growth patterns. The cytoplasm of the tumor cells was BRAF‐positive. The membranes and some tumor cell cytoplasm were also highly positive for PD‐L1 (clone 22C3; Dako) (TPS ≥ 95%). There was a marked increase in the number of CD4‐positive lymphocytes compared to the lymph node involvement at the time of diagnosis; however, the increase in CD8‐positive lymphocytes was limited compared to what was observed in the pleural lesions.
FIGURE 3
FIGURE 3
18F‐fluorodeoxyglucose positron emission tomography (18F‐FDG‐PET) images before the start of dabrafenib‐trametinib (DT) treatment showed strong accumulation of FDG in the axillary lymph nodes and diffuse accumulation of FDG on the pleura. After 1 year of treatment, the abnormal accumulation in the axillary lymph nodes disappeared, but the diffuse pleural accumulation repeatedly worsened and decreased.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Paik PK, Arcila ME, Fara M, Sima CS, Miller VA, Kris MG, et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol. 2011;29:2046–2051. 10.1200/JCO.2010.33.1280 - DOI - PMC - PubMed
    1. Elizabeth D, Nir P, Hovav N, Mira W, Amir O. BRAF mutant lung cancer: programmed death ligand 1 expression, tumor mutational burden, microsatellite instability status, and response to immune check‐point inhibitors. J Thorac Oncol. 2018;13(8):1128–1137. 10.1016/j.jtho.2018.04.024 - DOI - PubMed
    1. US Food and Drug Administration . FDA grants accelerated approval to dabrafenib in combination with trametinib for unresectable or metastatic solid tumors with BRAF V600E mutation, 2023. Accessed 24 November 2023. https://www.fda.gov/drugs/resources‐information‐approved‐drugs/fda‐grant...
    1. Planchard D, Besse B, Groen HJM, Hashemi SMS, Mazieres J, Kim TM, et al. Phase 2 study of dabrafenib plus trametinib in patients with BRAF V600E‐mutant metastatic NSCLC: updated 5‐year survival rates and genomic analysis. J Thorc Oncol. 2022;17:103–115. 10.1016/j.jtho.2021.08.011 - DOI - PubMed
    1. Philip B, Martin R, Tobias O. Outcome of first‐line treatment with pembrolizumab according to KRAS/TP53 mutational status for nonsquamous programmed death‐ligand 1‐high (≥50%) NSCLC in the German National Network Genomic Medicine Lung Cancer. J Thorac Oncol. 2023;S1556‐0864(23):02423‐1. 10.1016/j.jtho.2023.12.015 - DOI - PubMed

Publication types