A 69-Year Old Man With Metastatic BRAF V600E-Mutated Metastatic NSCLC - Episode 1

A 69-Year-Old Male With BRAF V600E+ mNSCLC

April 14, 2020

Hossein Borghaei, DO:Today we’ll be discussing the treatment of patients with aBRAFmutation, the history of non—small cell lung cancer, and talk about some of the unique features of this particular mutation. To highlight some of these differences, I’m going to present a case and then discuss the treatment of this particular patient and talk about how we usually approach a patient with non–small cell lung cancer and aBRAFmutation.

The case involves a 69-year-old male who comes in with a chronic dry cough and dyspnea on exertion. He has a past medical history of hypercholesterolemia, and he has a 20-pack-year smoking history. He quit about 6 years ago. His hypercholesterolemia is under control with medical management. On physical examination, the only abnormality is that he has decreased breath sounds on auscultation.

In terms of the clinical work-up, his laboratory test results are within the normal limit. His chest x-ray shows a solid mass of about 4 cm. This is confirmed by a CT [computed tomography] scan that shows a 3.7-cm pulmonary nodule in the right lobe. He has an ipsilateral mediastinal and subcarinal lymphadenopathy. And then he undergoes a bronchoscopy for tissue acquisition and diagnosis, and unfortunately, he is diagnosed with a metastatic lung cancer, adenocarcinoma subtype. The MRI [magnetic resonance imaging] does show a small brain lesion. He then undergoes molecular testing. His PD-L1 [programmed death-ligand 1] comes back as having TPS [tumor proportion score] of 20%, and hisEGFR, andALK,andROSmutation testing come back as being negative. However, he does have aBRAFV600E mutation. He’s then staged as having a T2aN2M1b metastatic adenocarcinoma with aBRAFV600E mutation. He’s got an excellent performance status.

This I would say is a typical patient who comes to our clinic. This patient was started on targeted therapy with a combination of dabrafenib, which is given at a dose of 150 mg by mouth twice daily, plus trametinib at a dose of 2 mg by mouth on a daily basis. He achieves a partial response and has been able to sustain this. As far as adverse effects are concerned, he has grade 1 fatigue, which again, is common for this type of therapy. But he continues treatment without any other significant toxicities. Imaging is repeated at 3 months, 6 months, and 9 months, and he still has a sustained partial response.

This case highlights several important things. I think the one thing that we have to get out and discuss is that we would not be able to treat these patients with targeted therapies that are well tolerated and are highly effective if it wasn’t for the molecular testing process. Therefore, I think one of the most significant things that I would like to highlight about this case is that everyone with a history of metastatic non—small cell lung cancer who comes to a clinic should undergo extensive molecular testing to find these mutations.

Overall, the literature suggests thatBRAFmutations are found in about 2% to 4% of all patients with metastatic adenocarcinoma. It’s not a large number, we realize that. But I think going through the case and reviewing the literature, hopefully you will see that it is important for the well-being of the patients that these minor mutations, if you want, are also detected. We all have heard stories aboutEGFR, ALK,and how effective these treatments are. And I think we’re learning that there are more and more of these driver mutations or targetable mutations for which we have very effective treatment options. And again, I cannot emphasize enough how important it is to have the molecular testing done in virtually 100% of our patients who come in with a diagnosis of lung cancer to be able to find these minor mutations.

Transcript edited for clarity.

Case: A 69-Year Old Man With MetastaticBRAFV600E—Mutated Metastatic NSCLC

Initial presentation

  • A 69-year old man presented with a chronic dry cough and dyspnea on exertion
  • PMH: history of hypercholesterolemia, medically treated; 20 pack-year smoking history, quit 6 years ago
  • PE: decreased breath sounds on auscultation

Clinical workup

  • Labs: WNL
  • Chest X-ray showed a ~4-cm
  • Chest/abdomen/pelvic CT showed a 3.7-cm solid pulmonary lesion in the right lobe, ipsilateral mediastinal and subcarinal lymph node involvement
  • Bronchoscopy biopsy of the lung lesion and lymph nodes revealed lung adenocarcinoma
  • Contrast-enhanced MRI of the head showed a small brain lesion
  • Molecular and biomarker testing:
    • PD-L1 TPS 20%
    • EGFR-, ALK-,BRAFV600E+,ROS1-
  • Stage T2aN2M1b; ECOG PS 0

Treatment and Follow-Up

  • Patient started on dabrafenib 150 mg PO qDay BID + trametinib 2 mg PO qDay; achieved partial response
    • Patient developed intermittent grade 1 fatigue, which was tolerable; continued treatment
  • Imaging at 3, 6 and 9 months showed sustained partial response