A Real-Life Cohort Reveals Promising Results from Israel
Published online in April 2020 in the journal Clinical Lung Cancer, a study by Dudnik et al. has brought to light critical insights into the treatment of BRAF-mutant advanced non-small cell lung cancer (NSCLC). This research examined the effectiveness and safety of treating this condition with BRAF inhibitors (BRAFi), alone or in combination with MEK inhibitors (MEKi).
Non-small cell lung cancer accounts for a significant majority of lung cancer cases and remains one of the leading causes of cancer-related deaths globally. The discovery of specific molecular mutations that contribute to the growth of cancer, such as mutations in the BRAF gene, presents an opportunity for targeted therapy, which has been a significant step forward in the treatment of this disease.
Study Design and Patient Groups
The study identified 58 consecutive patients with BRAF-mutant advanced NSCLC from nine Israeli medical centers, treated between 2009 and 2018. The patients were divided into five groups based on the mutation subtype and treatment:
Group A1: V600E mutation, treated with BRAFi only.
Group A2: V600E mutation, treated with BRAFi plus MEKi.
Group A3: V600E mutation, not treated with BRAFi.
Group B1: Non-V600E mutation, treated with BRAFi with or without MEKi.
Group B2: Non-V600E mutation, not treated with BRAFi.
The main objectives were to evaluate the safety and efficacy of these treatments and to measure the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
Key Findings of the Study
The study found that the combination of BRAFi and MEKi was superior to BRAFi monotherapy. Specifically, the ORR was substantially higher in Group A2, which received the combination therapy, compared to those in Group A1, who received only BRAFi. PFS also favored the combination therapy, with a median of 5.5 months compared to 1.2 months for BRAFi alone (P = .04).
The overall survival median was 9.5 months for patients treated with the combination therapy compared to 1.7 months for BRAF monotherapy in Group A1 and 7.1 months for group B1. Although the overall survival for the combination did not reach statistical significance when compared to monotherapy, the trend suggested a potential benefit.
The study’s safety evaluation indicated that while the safety profiles slightly differed, the discontinuation rates due to adverse effects were similar between BRAFi and BRAFi plus MEKi treatments, suggesting that the combination therapy does not significantly increase treatment-related risks.
Implications and Future Directions
The outcomes of this real-life cohort suggest that the activity and safety of BRAFi combined with MEKi in BRAF-mutant NSCLC are comparable to those observed in controlled clinical trials, reinforcing the potential of the combination therapy as an effective option for these patients.
These results hold particular importance because they reflect a real-world scenario—which can often present different challenges and outcomes compared to controlled clinical trial environments—and can provide valuable information for oncologists and patients when making treatment decisions.
However, the authors of the study emphasize the necessity of further research to understand the long-term impact of BRAFi and MEKi combination therapy on the natural history of BRAF-mutant NSCLC.
Potential for Personalized Cancer Therapy
The study presents a strong case for personalized medicine in lung cancer treatment, where therapy is tailored to the genetic characteristics of an individual patient’s cancer. BRAF and MEK inhibitors target specific mutations and pathways that are crucial for cancer cell survival and proliferation, representing a step away from one-size-fits-all treatment approaches.
Doing More With Real-Life Data
Real-life data such as this can bridge the gap between clinical trials and everyday clinical practice, allowing health care providers to make more informed decisions and improve patient outcomes. Such studies have the potential to enhance our understanding of the therapies in a broader, more diverse patient population.
References
1. Dudnik, E., Bar, J., Peled, N., et al. (2019). 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. Clinical Lung Cancer, 20(4), 278-286.e1. doi:10.1016/j.cllc.2019.03.007
Keywords
1. BRAF inhibitors NSCLC
2. MEK inhibitors combination therapy
3. BRAF-mutant lung cancer
4. Targeted therapy for lung cancer
5. Advanced NSCLC treatment options
DOI: 10.1016/j.cllc.2019.03.007
As research continues, more light will be shed on optimal treatment strategies for BRAF-mutant advanced NSCLC. This study provides hope and direction for more effective therapies, and most importantly, a better prognosis for patients grappling with this challenging disease.