Treating a Patient With BRAF V600E-Mutated Small Cell Lung Cancer

Fawzi Abu Rous, MD, Henry Ford Health, Detroit, Michigan, discusses the treatment of a patient with BRAF V600E-mutated small cell lung cancer (SCLC) who experienced a durable response with targeted therapy. 

Key Clinical Takeaways

• Patient Profile: 54-year-old male, athletic, nonsmoker; diagnosed July 2020 with small cell lung cancer (SCLC) presenting with left lung mass and bone metastases.
• Initial Therapy: Standard-of-care carboplatin + etoposide + atezolizumab; patient progressed unusually rapidly, inconsistent with typical SCLC course.
• Atypical Features Prompting NGS:
  • Young, athletic, nonsmoking patient (uncommon for SCLC).
  • Rapid progression despite frontline chemo-immunotherapy.
• Molecular Findings: BRAF V600E mutation detected on next-generation sequencing (NGS); mutation well-established in NSCLC and melanoma, but rare in SCLC.
• Targeted Treatment: Initiated dabrafenib + trametinib (BRAF/MEK inhibitors) January 2021.
  • Durable response for ~4 years to date.
  • Minor oligoprogression events managed with localized radiation.
• Clinical Significance:
  • Demonstrates de novo BRAF V600E mutation in SCLC, not acquired post-therapy.
  • Highlights potential for targeted therapy in molecularly selected SCLC patients.
• Practice Implications:
  • Consider NGS/molecular profiling in SCLC patients with atypical clinical features (young age, no smoking history, unusual disease behavior, or atypical treatment response).
  • Identify actionable alterations (e.g., BRAF V600E) that may expand therapeutic options beyond standard chemo-immunotherapy.
  • Multidisciplinary management, including integration of targeted therapy + radiation oncology, can optimize long-term outcomes.

Transcript:

Hi everyone, my name is Fawzi Abu Rous, I'm a thoracic medical oncologist at Henry Ford Cancer Institute in Detroit, Michigan. Today, I'm going to be talking about our recent publication in Clinical Lung Cancer titled “Small cell lung cancer with de novo BRAF V600E mutation and durable response to targeted therapy: A case report.”

This paper describes one of our patients who is a 54-year-old male who was diagnosed with small cell lung cancer after having a cough for some time and the diagnosis was made in July of 2020. His PET scan, that you can see in the paper, showed that he has a mass in the left lung as well as some bone metastases, so some spread of the cancer to his bone. Based on that, we went ahead and did a biopsy of the lungs and the bones to prove metastatic disease, and the biopsy showed small cell lung cancer. 

We went ahead and treated the patient with standard-of-care treatment, which is a combination of chemo- and immunotherapy, so carboplatin-etoposide, and immunotherapy called atezolizumab but unfortunately, the patient progressed relatively rapidly, and this is relatively inconsistent with the regular or the typical behavior of small cell lung cancer, which typically tends to progress but later in time or tends to respond to the first few cycles of chemotherapy with immunotherapy. The fact that our patients also had some atypical characteristics for someone who would develop small cell lung cancer, being an athletic, young male, and also no history of smoking, which typically patients with small cell lung cancer tend to have history of smoking or even high history of or high-pack smoking history. 

Based on the atypical response to treatment and the atypical characteristics that our patient had that are not fitting with small cell lung cancer, we sent his tissue for NGS [next-generation sequencing] and the results were shockingly but pleasantly surprising. The results showed a mutation called BRAF V600E, which is a well described mutation in lung cancer, in non-small cell lung cancer as well as other tumors, particularly in melanoma. The good news is that this particular mutation, it's well described but also has a targeted therapy or even more than 1 option of targeted combinations. Based on those results or the results of the NGS, we went ahead and treated our patient with a combination of dabrafenib and trametinib, which are 2 medications that are designed to target this alteration in non-small cell lung cancer and also in other solid malignancy and the patient had a wonderful response. He started this treatment, I believe in January 2021, and up until now, almost 4 years later, he continues to enjoy a durable response. He had some minor, what we call oligoprogression, or limited progression here and there, but all of them were successfully managed with the help of our radiation oncology team. 

We believe that this is a unique case of a patient with small cell lung cancer who has de novo BRAF V600 gene mutation, which means that this mutation was present from the beginning and did not develop as a result of a resistance to a certain treatment. The few unique features that we can highlight in this case is the presence of this mutation in small cell lung cancer, because it's typically more common relatively in patients with non-small cell lung cancer and other solid malignancies, and the fact that this patient had small cell lung cancer being a young patient with no history of smok[ing]. 

Lessons that we can learn from this case is whenever we face an atypical case or a patient with small cell lung cancer who is not fitting the general description or general characteristics of patients with small cell lung cancer, whether being a young patient, no history of smoking, or if the disease is not behaving like your typical small cell lung cancer being either having a very limited progression, a very slow growth rate, or even lack of response to the typical or to the standard of care therapies for small cell lung cancer, we would highly recommend sending the tissue to sequencing or what we call molecular profiling because those patients might have something or targetable alteration that you can utilize and treat the patients with similar to our case.

Source: 

Kulkarni R, Zeine E, Potugari B, et al. Small cell lung cancer with de novo BRAF V600E mutation and durable response to targeted therapy: A case report. Clin Lung Cancer. Published online: February 20, 2025. doi: 10.1016/j.cllc.2025.02.012