YO36 - A case of BRAF V600E mutated non-small-cell lung cancer with pleomorphic features

Case summary

The frequency of BRAF mutation in non-small-cell lung cancer (NSCLC) is 1–2%. Some studies showed the patients with the mutation have poor outcomes to chemotherapy. Use of dabrafenib plus trametinib in BRAF V600E mutated NSCLC showed improvement in clinical outcomes of treatment-naïve and previously treated patients in phase II trials.

Pulmonary pleomorphic carcinoma (PPC) is a rare histologic subtype of NSCLC characterized by aggressive features with poor prognosis. Many of PPCs are reported to be resistant to chemotherapy and radiotherapy. Some types of targetable oncogenes have been detected in PPCs. However, the significance of BRAF mutation in PPC remains unclear.

Here we describe a patient with BRAF V600E mutated NSCLC with pleomorphic feature treated with BRAF and MEK inhibitor.

The patient is a 53-year-old woman. Chest CT scan revealed the mass invading the chest wall in the right middle lobe, hilar and mediastinal lymph node metastasis, and pleural dissemination. Biopsy from the primary tumor showed NSCLC-NOS. Gene analysis revealed the tumor was EGFR wild type, ALK/ROS-1 fusion negative, and PD-L1 TPS was 0%. Clinical stage was T4 N2 M1a, Stage IVA.

She received CDDP+GEM, Pemetrexed, and TS-1 sequentially, however, no response was obtained by these therapies. At the time of disease progression, right middle and lower lobe atelectasis was caused by the primary tumor and lymph nodes enlargement, and multiple bone metastasis emerged.

Re-biopsy was performed from the chest wall invasion site. The sample showed poor differentiated epithelial tumor cells and spindle cells suggesting pleomorphic feature and BRAF V600E was detected by next generation sequencing test.

Based on the result, we started dabrafenib plus trametinib therapy. The primary lesion and hilar lymph nodes rapidly shrunk resulting in atelectasis resolving on the chest X-ray in two weeks. The CT scan revealed dramatic tumor response in all metastatic legions. The response continued for about 10 months.

To best of our knowledge, few BRAF mutation positive NSCLC with pleomorphic feature cases have been reported. This case suggests that BRAF V600E mutation is also an important therapeutic target in PPC as much as in other histology.

Clinical trial identification

Editorial acknowledgement