## 3 Discussion
One patient, who had poorly responded to first-line treatment with platinum-based chemotherapy, developed progressive disease (PD) after receiving second line treatment with dabrafenib plus trametinib; two other patients experienced a PFS of 2.0 months and 4.0 months with first line anti-BRAF target therapy; and, finally, one patient achieved a PFS of 3.5 months after second line nivolumab plus chemotherapy [11]. Considering the differences between the genetic background of Caucasians and Asians, we propose that studying _BRAF_ mutations in NSCLC Asian patients may be of great significance to study the molecular complexity of these mutations. Although results from previous small-sample retrospective analyses have underlined an association between PD-L1 expression and _BRAF_-mutated NSCLC patients [22, 23], the objective response rate to single anti-PD-(L)1 agents in _BRAF_-mutant lung adenocarcinoma is only 10-30%, with a median PFS of 2-4 months. Analogous results have been observed in studies of wild-type NSCLC treated with second-line immune-checkpoint inhibitor (ICI) monotherapy [14, 24]. Specifically, no PFS differences were seen between V600E and non-V600E mutant NSCLC treated with a single-agent ICI [24]. Instead, a recent case report has shown that first-line ICI plus chemotherapy produces a durable response in a _BRAF_ exon 15 p.V600E mutated lung cancer, with a PFS of about 20 months [25]. Based on these results, it would be interesting to assess the effects of chemo-immunotherapy combination in _BRAF_ exon 15 p.K601E positive NSCLC. Our report is interesting for several reasons. First, the clinical presentation of our case is quite atypical in that metastatic peritoneal carcinomas (MPC) is a rare NSCLC complication in clinical practice, often suggesting the presence of potentially targetable mutations [26]. As previously reported, the profile of MPC NSCLC is predominantly adenocarcinoma, often harboring _EGFR_ mutations or ALK rearrangements. Notably, ascitic fluid cytology tests can successfully detect _EGFR_ mutations in about 60% of patients whose tumor specimen harbor the mutation [27]. The presence or absence of a driver oncogene has been shown to determine an OS of 12.0 months versus 2.5 months, thereby drastically improving the prognosis [27, 28]. As of today, though, data on MPC in _BRAF_-mutated NSCLC are still missing. A second interesting aspect of our report is that our patient carried the atypical _BRAF_ exon 15 p.K601E mutation, for which there is no clinical experience describing the efficacy of first-line chemo-immunotherapy combination; moreover, there are only conflicting reports regarding the sensitivity of this rare mutation to targeted therapy. Specifically, after receiving first-line treatment with pembrolizumab plus carboplatin plus pemetrexed, our patient experienced a PFS of 8-9 months. Unfortunately, owing to cancer progression and subsequent death, we were unable to evaluate our patient's PFS after receiving second-line targeted therapy. A final interesting aspect arising from this report is the hypothesis that our patient might have been affected by a biclonal disease given the absence of _BRAF_ mutations in the pleural effusion. Such suspicion was clinically verified without resorting to invasive evacative paracentesis but by rapidly controlling the peritoneal disease with dabrafenib plus trametinib treatment. However, the treatment failed to stop the rapid clinical lung and pleural progression. In this regard, we speculate that BRAF and MEK inhibitors might only partially act against _BRAF_ class II exon 15 p.K601E-mutation.