A phase I study of anlotinib with concurrent chemoradiotherapy for limited-stage small cell lung cancer.

Abstract

8579 Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for limited-stage small-cell lung cancer (LS-SCLC). However, LS-SCLC remains an area of high unmet medical need. Anlotinib is an antiangiogenic multi-target tyrosine kinase inhibitor. In the phase II ALTER-1202 trial, anlotinib significantly improved clinical outcomes in advanced small-cell lung cancer. We report here a phase 1 trial of anlotinib with CCRT for LS-SCLC. Methods: This is a prospective, single-arm, phase I clinical trial using a 3+3 design. Patients aged between 18 and 75 with previously untreated LS-SCLC, PS 0-1 and adequate organ function are eligible. Patients received anlotinib (12mg, qd, d1-14, q3w) and chemotherapy (etoposide, 100 mg/m2, d1-3, q3w and cisplatin, 25 mg/m2, d1-3, q3w) for cycle 1, then anlotinib [dose escalation at 3 levels (DL1-3) 8mg, 10mg and 12mg, qd, d1-14, q3w], chemotherapy (etoposide, 50 mg/m2, d1-5, q4w and cisplatin, 25 mg/m2, d1-3, q4w) and thoracic radiotherapy (60-66 Gy in 30-33 daily 2-Gy fractions starting on day 1 of cycle 2) for cycles 2–3, then anlotinib (12mg, qd, d1-14, q3w) and chemotherapy (etoposide, 100 mg/m2, d1-3, q3w and cisplatin, 25 mg/m2, d1-3, q3w) for cycles 4-6. Cycles 5-6 were given as appropriate according to the patient's physical condition. Prophylactic cranial radiation was given according to the judgment of the investigator after CCRT. The purpose of this study is to determine the maximum tolerated dose (MTD) of anlotinib when combination with CCRT. Results: Twelve patients were enrolled from May 2020 to September 2021. No DLTs were observed in DL1 (3 patients) or DL2 (3 patients). At DL3 (6 patients), 1 patient had a DLT of grade 3 pulmonary embolism. Grade 3 adverse events were white blood cell count decreased, neutrophil count decreased, lymphocyte count decreased, hypertension, albumin decreased and pulmonary embolism. One patient had grade 3 pulmonary embolism and grade 4 neutrophil count decreased in DL3 at cycle 1. One patient had grade 2 radiation pneumonitis after cycle 5 and grade 1 radiation esophagitis at cycle 3 in DL3. One patient had grade 2 radiation esophagitis at cycle 3 in DL2. The MTD was not reached. Conclusions: Combined treatment with anlotinib and CCRT for limited-stage small cell lung cancer is well tolerated and further clinical investigation is warranted. Clinical trial information: NCT04882033.