A 69-Year Old Man With Metastatic BRAF V600E-Mutated Metastatic NSCLC - Episode 5

Adverse Effects and BRAF Inhibitors in mNSCLC

Hossein Borghaei, DO:As we have highlighted in this case, fatigue is something that happens. I have not encountered an antineoplastic regimen that does not cause fatigue, unfortunately. So, discussing fatigue and management of fatigue and emphasizing activity is important in combating treatment fatigue. That’s clearly one issue that I think must be discussed. But the BRAF-specific targeted therapies have some unique features that I think are worth highlighting, and that’s the fact that many patients develop photosensitivity, particularly if you use vemurafenib. Use of sunscreen and things like that are important. Maculopapular rash can happen.

But in particular, this patient population can suffer from this adverse effect that’s been labeled as squamoproliferative lesions. Basically patients can develop skin cancers and squamous cell carcinomas of the skin and keratosis. These are typically the kind of adverse effects that leads me to ask our colleagues in the dermatology division to see these patients along with us for routine checkups and management of these squamous cell carcinomas of the skin that might arise.

This seems to be related to the MEK pathway, and again it’s one of the things that, at least in my practice, I encourage patients to have a visit with a dermatologist, initially for a routine general check and then have regular follow-ups so that when these lesions do come up, they can be managed appropriately, and most of them can be managed by small incisions. But as I said, this is a unique feature that we see in our patients who are treated with the targeted therapies forBRAFV600E.

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