A 62-Year-Old Woman With BRAF V600E+ Metastatic NSCLC

Joshua Bauml, MD:The case we’re discussing today is that of a 62-year-old woman who presents with metastatic non—small cell lung cancer.…She initially presented with a cough and shortness of breath. She had imaging that revealed a mass in the right lung as well as what was concerning for metastases in the liver. The MRI of her brain did not reveal any metastases.

She had a bronchoscopic biopsy of her lung mass and her mediastinal lymph nodes, and they revealed an adenocarcinoma of the lung. This tumor was then sent for molecular testing using a next-generation sequencing panel. This revealed aBRAFV600E mutation.

Notably, this panel included other molecular targets that we need to look for such asEGFR, ALK, ROS-1, RET,andNTRK. It was a comprehensive…mutation and translocation profile. The only alteration…noted wasBRAFV600E.

The patient came in for treatment and was started on dabrafenib and trametinib. She had some nausea and vomiting but otherwise tolerated the treatment well and, at her first scan assessment, had achieved a partial response. She then continued the treatment, and at 9 months follow-up had a sustained partial response.

This is really a typical presentation ofBRAFV600E—mutant non–small cell lung cancer. Unfortunately, many patients with non–small cell lung cancer present with metastatic disease and, in this case, it’s important to remember that molecular testing is essential for any patient with metastatic nonsquamous, non–small cell lung cancer, regardless of their smoking history or any other epidemiologic factors. And that’s critical specifically for looking forBRAFmutation becauseBRAFmutations, in contrast toEGFRandALKalterations, tend to occur in patients who have a history of tobacco exposure.

In this case, our patient had a 25-pack-year smoking history. Now, historically, some might have said, “Oh, well, we don’t need to do molecular testing. We’re not going to find anEGFRmutation.” So, first of all, that’s wrong, and we should definitely be doing a comprehensive molecular test regardless of their smoking history. But it is important to note that alterations such asBRAFandMEKhave a higher incidence in patients with a history of tobacco exposure. So it’s really important to do this comprehensive molecular profile.

And when we think about that molecular profiling, it’s really important…we know not only that it was done, but what test was used. Does the test look atBRAFV600E? Can the test reliably identify fusions and translocations? If it hasn’t, it’s not that the test is worthless—it just…informs what further testing you may need to do in the future.

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