How To Select Between Treatment Options for BRAF V600E–Mutated NSCLC
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Key Points
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Standard treatment options for BRAF V600E–mutated non-small cell lung cancer (NSCLC) include targeted therapy combinations, immunotherapy, and chemoimmunotherapy.
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Between the two approved targeted therapy combinations, phase II data show encorafenib plus binimetinib may have slightly more favorable safety and efficacy.
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Retrospective analyses suggest frontline immunotherapy–based treatment may be more beneficial than targeted therapy for specific patient subgroups.
Treatment Options for BRAF V600E–Mutated NSCLC
On the Oncology Brothers podcast, community medical oncologists, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, met with Gregory Riely, MD, PhD, a thoracic medical oncologist from Memorial Sloan Kettering Cancer Center, to discuss treatment options for BRAF V600E–mutated NSCLC.
The BRAF V600E mutation occurs in roughly 1.5% to 2% of patients with NSCLC. Contrary to many other NSCLC mutations, BRAF V600E–mutated NSCLC is susceptible to immune checkpoint inhibitors, prompting oncologists to choose between targeted therapy, immunotherapy, or chemoimmunotherapy.
Targeted Therapy for BRAF V600E–Mutated NSCLC
In BRAF V600E–mutated NSCLC, the combination of a BRAF inhibitor and a MEK inhibitor was shown to improve response rates versus BRAF inhibition alone. To date, two BRAF plus MEK inhibitor combinations have been approved for this population based on phase II trials: encorafenib plus binimetinib and dabrafenib plus trametinib.
While there are no head-to-head comparisons of the combinations, more recent data from the PHAROS study suggest that encorafenib plus binimetinib may have slightly more favorable overall survival and progression-free survival outcomes compared with dabrafenib plus trametinib in treatment-naive patients. In addition, encorafenib plus binimetinib is associated with lower rates of pyrexia. Considering these data, the doctors all shared a preference for encorafenib and binimetinib in patients with BRAF V600E–mutated NSCLC.
If a patient struggles to tolerate a BRAF and MEK inhibitor combination, oncologists could consider dropping the MEK inhibitor, although BRAF-related cutaneous toxicities can actually increase with single-agent BRAF inhibition compared with a combination.
Targeted Therapy Versus Immunotherapy in BRAF V600E–mutated NSCLC
Targeted therapies are valuable treatment options for BRAF V600E–mutated NSCLC across treatment lines. However, growing evidence from studies like FRONT-BRAF suggest that frontline immunotherapy-based treatment may have a greater benefit for select patient populations, including those with high PD-L1 expression or a history of smoking.
Based on these recent findings, Dr. Riely leans more toward frontline immunotherapy the higher a patient’s PD-L1 score is, especially if they have any smoking history. However, targeted therapy remains the obvious treatment choice for patients without a history of smoking and with low or no PD-L1 expression. Importantly, using immunotherapy-based treatment in the frontline setting, does not preclude patients from continuing on to a BRAF and MEK inhibitor combination if they have disease progression.