Extraordinary clinical benefit to sequential treatment with targeted therapy and immunotherapy of a BRAF V600E and PD-L1 positive metastatic lung adenocarcinoma.

Background: The treatment algorithm for metastatic non-small cell lung cancers (NSCLCs) has been evolving rapidly due to the development of new therapeutic agents. Although guidelines are provided by National Comprehensive Cancer Network (NCCN) for treatment options according to biomarker testing results, sequentially applying the three main modalities (chemotherapy, targeted therapy and immunotherapy) remains an ad hoc practice in clinic. In light of recent FDA approval of dabrafenib and trametinib combination for metastatic NSCLCs with BRAF V600E mutation, one question arises due to insufficient clinical data is if the targeted therapy should be used before immunotherapy in patients with both BRAF V600E and PD-L1 expression.

Case presentation: We present a case of 74-year-old female, former smoker with metastatic lung adenocarcinoma. The BRAF V600E mutation among other abnormalities was identified by comprehensive genomic profiling. The patient had an excellent 2-year response to the combination of pemetrexed and sorafenib. The patient was then treated with dabrafenib due to the presence of the BRAF V600E mutation and intolerance to cytotoxic chemotherapy. Not only the patient had an 18-month durable response to dabrafenib, she experienced outstanding quality of life with no serious adverse effects. At the time of symptomatic progression, the patient was then treated with two cycles of pembrolizumab based on her positive PD-L1 staining (90%). She had early response and came off pembrolizumab due to side effects. Seven months after initiation of pembrolizumab, the patient is off all the therapy and is currently asymptomatic. The patient is surviving with metastatic disease for over 7 years as of to date.

Conclusions: By appropriately sequencing the three main modalities of systemic therapies, we are able to achieve long-term disease control with minimal side effects even in a geriatric patient with multiple comorbidities. We argue that it is reasonable to first use a BRAF inhibitor before considering immunotherapy for NSCLCs positive for both BRAF V600E and PD-L1.