Capecitabine and Temozolomide in Advanced Lung Neuroendocrine Neoplasms

Background Patients with advanced lung neuroendocrine neoplasms (NENs) have few treatment options. Capecitabine and temozolomide have recently showed significant activity in patients with pancreatic neuroendocrine tumors (NETs), but data in lung NETs are limited. Methods We retrospectively reviewed the records of patients treated at a large referral center to identify patients seen between January 2008 and September 2018 with metastatic lung NENs who received treatment with capecitabine and temozolomide (CAPTEM). Patients with small cell lung cancer were excluded. The primary endpoint was overall response rate per RECIST 1.1. Secondary endpoints included progression‐free survival, overall survival, and toxicity. Results Twenty patients were identified who received treatment with capecitabine and temozolomide. Fourteen (70%) had typical lung NETs, five had (25%) atypical carcinoids, and one (5%) had disease defined as a large‐cell neuroendocrine carcinoma. Nineteen patients were evaluable for response. Six (30%) patients exhibited a best response of partial response per RECIST 1.1 criteria, 11 (55%) stable disease, and 2 (10%) progressive disease; objective response rate was 30%, and disease control rate was 85%. Eleven patients eventually progressed, only six of whom exhibited progression per RECIST 1.1 criteria. Median progression‐free survival was 13 months (95% confidence interval [CI], 4.4–21.6 months). Median overall survival was 68 months (95% CI, 35.3–100.7 months). Toxicity profile was mild with mainly grade 1, expected toxicities. Six patients required dose reduction because of toxicity. Conclusion The CAPTEM regimen is associated with a high response rate and a relatively tolerable toxicity profile in lung NENs. This regimen warrants further exploration in a prospective clinical trial. Implications for Practice Patients with advanced lung neuroendocrine neoplasms have very few systemic treatment options. The capecitabine and temozolomide regimen has previously shown significant activity in patients with pancreatic neuroendocrine tumors (NETs) but has not been explored in metastatic lung NETs. This study showed that this regimen is associated with a high response rate (30%) and a relatively tolerable toxicity profile in this population. Patients with advanced lung neuroendocrine tumors (NETs) have limited treatment options. Everolimus is the only FDA‐approved systemic therapy. This study explored a regimen of capecitabine and temozolomide in patie