Case report from a study investigating everolimus combined with paclitaxel and carboplatin in patients with advanced large cell neuroendocrine carcinoma of the lung (LCNEC)
Targeted therapies are discussed as an approach to improve outcome in neuroendocrine tumors of the lung. With current treatment options like platinum derivates and etoposide, large cell neuroendocrine carcinoma of the lung (LCNEC) patients have a poor prognosis.
Everolimus (RAD001) is an inhibitor of mTOR, a component of the PI3K/AKT/mTOR pathway known to be dysregulated in neuroendocrine tumors (NETs).
In the presented trial for advanced LCNEC patients, daily RAD001 is combined in first-line with carboplatin and paclitaxel, a standard chemotherapy for this population. Enrolled patients receive 4 cycles of combined treatment followed by RAD001 maintenance therapy. The primary endpoint is the proportion of progression-free patients after 3 months. Main inclusion criteria are histologically confirmed stage IV LCNEC and at least one positive neuroendocrine marker. Main exclusion criteria are symptomatic CNS metastases and prior treatment for advanced LCNEC.
Here a case report of a 56-year old patient with stage IV LCNEC enrolled in this trial is presented. The tumor histologically revealed NSCLC morphology of the large-cell type and a considerable CD56 and synaptophysin staining as well as a proliferation rate of more than 60% in Ki67 staining. The patient received in first-line 4 cycles of carboplatin and paclitaxel combined with RAD001 and subsequently RAD001 monotherapy for further 9 months. The tumor response revealed as per RECIST a partial remission during the first 3 months and an ongoing stabilization of the tumor for further 9 months before a disease progression was detected 12 months after initial diagnosis. At the fifth cycle of a second-line treatment with carboplatin and etoposide, the patient has still a stable disease 16 months after initial diagnosis of LCNEC.
These data show that a combined therapy of carboplatin and paclitaxel with mTOR-inhibitor RAD001 in first-line might be a promising approach for more efficient treatment of LCNEC patients.