Progress Made in Treating BRAF V600E+ Metastatic NSCLC

Joshua Bauml, MD:BRAFV600E—mutant non–small cell lung cancer represents one of the great opportunities that we have had in the lung cancer community to take advantage of the hard work of our colleagues in other tumor types.

…Our colleagues who treat melanoma have already done a lot this work to help identifyBRAFas a target and to show that these drugs work in that space. And we were able to show through these trials led by Dr David Planchard, MD, PhD, that dabrafenib and trametinib also have activity inBRAFV600E—mutant non–small cell lung cancer.

And so in terms of looking toward the future, I think the key thing…we should do is continue looking at what they’re doing in melanoma because the incidence ofBRAFmutation is much higher there.

One thing that I think…is very reassuring is that in contrast to many other tyrosine kinase inhibitors, in melanoma, the combination of dabrafenib and trametinib, with immunotherapy or overlap in those drugs, has not been associated with the level of toxicity that we see, for instance, when immunotherapy overlaps with EGFR inhibitors or ALK inhibitors. So that’s reassuring toward the future, and hopefully we’ll be able to combine immunotherapy with targeted therapy in this space, given the tolerability of these drugs together. But I think it’s really a wide-open space to try to improve outcomes for these patients.

Transcript edited for clarity.

Case: A 62-Year-Old Woman With MetastaticBRAF^V600E-Mutated NSCLC

Initial Presentation

• A 62-year-old woman presented with a 4-month history of chronic cough, dyspnea, loss of appetite and weight loss
• PMH/SH: 25 pack-year smoking history, quit 12 years ago
• PE: Right-sided wheezing on auscultation

Clinical Workup

• Labs: WNL
• Chest/abdomen/pelvic CT showed a 2.5-cm solid pulmonary lesion in the left inferior lobe, ipsilateral peribronchial lymph node involvement and multiple small hepatic lesions
• Bronchoscopic biopsy of the lung lesion and lymph node revealed lung adenocarcinoma
• Contrast‐enhanced MRI of the head showed no evidence of metastases
• Molecular and biomarker testing: BRAF^V600E+,EGFR-, ALK-, ROS1-,PD-L1 0%
• Stage T1cN1M1c; ECOG PS 0

Treatment and Follow-Up

• Started on dabrafenib 150 mg PO qDay BID + trametinib 2 mg PO qDay; achieved a partial response
  • Patient developed intermitted nausea and vomiting, medically controlled
• Imaging at 3,6 and 9 months showed sustained partial response