Therapies for advanced non‐small cell lung cancer (NSCLC) continue to become more sophisticated. Chemotherapeutics are giving way to newer approaches such as immune checkpoint inhibitors and targeted therapies for greater efficacy and improved outcomes. Dabrafenib plus trametinib combination therapy was first approved for the treatment of metastatic melanoma harboring the BRAF V600‐mutation in 2014. In 2017, the U.S. Food and Drug Administration approved the combination for patients with NSCLC with the same mutation based on an ≈ 65% response rate and median progression‐free survival of 10–11 months. BRAF mutations are a high‐frequency event in melanoma (≈ 50%), whereas the overall incidence in lung cancer is ≈ 2%, but similar in number, because of the high incidence of the disease. As a new approach in NSCLC treatment, dabrafenib plus trametinib has a unique toxicity profile that is likely unfamiliar to care providers in thoracic and general oncology who have not used the combination to treat patients with melanoma. Common adverse events such as pyrexia, fatigue, and nausea, as well as a range of less frequent cutaneous, ocular, and hemorrhagic events, can be observed during treatment with dabrafenib plus trametinib. Previous experience in metastatic melanoma revealed that these events can be effectively managed to improve patient quality of life and reduce unnecessary drug discontinuation. The aim of this review is to summarize treatment guidelines, along with key insights obtained from previous clinical‐trial and real‐world experience in patients with metastatic melanoma, to properly manage toxicities associated with dabrafenib plus trametinib for NSCLC. Implications for Practice The combination of dabrafenib plus trametinib has demonstrated substantial clinical activity in patients with BRAF V600E‐mutant non‐small cell lung cancer, leading to U.S. Food and Drug Administration approval. Although the combination has a manageable safety profile, many toxicities associated with the regimen may not be familiar to thoracic specialists or general oncologists. Extensive clinical experience with the combination in patients with metastatic melanoma has provided a wealth of strategies to identify and manage adverse events associated with dabrafenib plus trametinib. These can be used by medical oncologists to enhance early recognition of toxicities and facilitate effective management, thereby improving quality of treatment for patients.
Objective Childhood-onset systemic lupus erythematosus (cSLE) has higher rates of lupus nephritis (LN) than adult-onset SLE, often requiring intensive immunosuppression. This study examined North American practices and preferences for the low-dose EuroLupus cyclophosphamide (CYC) protocol, as compared to the high-dose National Institutes of Health (NIH) CYC protocol, to treat LN in cSLE. Methods A 35-item Web-based survey was distributed to Childhood Arthritis and Rheumatology Research Alliance (CARRA) and Pediatric Nephrology Research Consortium (PNRC) providers. The survey assessed participant demographics, CYC prescribing practices, perceptions of EuroLupus protocol, and LN vignette treatment decisions; 1 vignette was taken from a 2009 CARRA survey and responses were compared. Multivariable logistic regression analyzed provider factors associated with use of low- vs high-dose CYC. Results Responses were provided by 185/421 (44%) pediatric rheumatologists (CARRA) and 40/354 (11%) pediatric nephrologists (PNRC). Among respondents who prescribed CYC for pediatric LN over the past year (n = 135), half reported using EuroLupus. When presented with the same vignette about an adolescent with class IV LN, 32% of pediatric rheumatologists chose EuroLupus dosing in 2020, vs 6% in 2009. Provider factors associated with choosing the low-dose regimen were familiarity with the protocol (OR 4.2, P = 0.006) and greater perceived benefit (OR 1.6, P < 0.0001). Pediatric nephrologists had similar responses to the pediatric rheumatology providers. Overall, 78% of respondents perceived EuroLupus protocol efficacy to be equivalent to the high-dose protocol in cSLE LN. Conclusion Pediatric specialists are currently more likely to use low-dose CYC to treat cSLE LN than they were a decade ago. Nevertheless, familiarity with EuroLupus dosing remains low.
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