Kiyotaka Yoh1, Takashi Seto2, Miyako Satouchi3, Makoto Nishio4, Noboru Yamamoto5, Haruyasu Murakami6, Naoyuki Nogami7, Kaname Nosaki2, Takashi Kohno8, Koji Tsuta9, Shogo Nomura10, Takashi Ikeno10, Masashi Wakabayashi10, Akihiro Sato10, Shingo Matsumoto11, Koichi Goto11. 1. Department of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. Electronic address: kyoh@east.ncc.go.jp. 2. Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 3. Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan. 4. Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. 5. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. 6. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 7. Department of Thoracic Oncology, Shikoku Cancer Center, Matsuyama, Japan. 8. Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan. 9. Department of Pathology and Laboratory Medicine, Kansai Medical University, Osaka, Japan. 10. Clinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan. 11. Department of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
Abstract
OBJECTIVES: The LURET phase II study evaluated the efficacy and safety of the multikinase inhibitor vandetanib in patients with previously treatedRET-rearranged advanced non-small cell lung cancer (NSCLC). Among the eligible patients included in the primary analysis, the objective response rate met the primary endpoint (53 %, 90 % confidence interval [CI]: 31-74). Here, we report final survival outcomes of the LURET study. MATERIALS AND METHODS: Nineteen patients with previously treated RET-rearranged advanced NSCLC continuously received 300 mg of oral vandetanib daily. This final analysis provides updated data on progression-free survival (PFS), overall survival (OS) and safety. This study was registered with UMIN-CTR (number UMIN 000010095). RESULTS: Among the 19 patients in the intention-to-treat population, 42 % had been heavily treated with 3 or more prior chemotherapy regimens. The median PFS was 6.5 months (95 % CI, 3.9-9.3) as determined by an independent radiology review committee. The median OS was 13.5 months (95 % CI, 9.8-28.1) and the overall survival rate at 12 months was 52.6 % (95 % CI 28.7-71.9). The most common adverse events were hypertension (84.2 %), diarrhea (78.9 %), and rash acneiform (63.2 %). Overall, 11 patients (57.9 %) had adverse events leading to a dose reduction, although the safety profile was consistent with that reported in previous studies. CONCLUSION: Our results indicated that vandetanib enabled a prolonged and clinically meaningful PFS and OS in patients with previously treatedRET-rearranged advanced NSCLC at the updated final analysis. The safety profile was consistent with that reported in previous studies, although most of the patients experienced off-target adverse events besides RET.
OBJECTIVES: The LURET phase II study evaluated the efficacy and safety of the multikinase inhibitor vandetanib in patients with previously treatedRET-rearranged advanced non-small cell lung cancer (NSCLC). Among the eligible patients included in the primary analysis, the objective response rate met the primary endpoint (53 %, 90 % confidence interval [CI]: 31-74). Here, we report final survival outcomes of the LURET study. MATERIALS AND METHODS: Nineteen patients with previously treated RET-rearranged advanced NSCLC continuously received 300 mg of oral vandetanib daily. This final analysis provides updated data on progression-free survival (PFS), overall survival (OS) and safety. This study was registered with UMIN-CTR (number UMIN 000010095). RESULTS: Among the 19 patients in the intention-to-treat population, 42 % had been heavily treated with 3 or more prior chemotherapy regimens. The median PFS was 6.5 months (95 % CI, 3.9-9.3) as determined by an independent radiology review committee. The median OS was 13.5 months (95 % CI, 9.8-28.1) and the overall survival rate at 12 months was 52.6 % (95 % CI 28.7-71.9). The most common adverse events were hypertension (84.2 %), diarrhea (78.9 %), and rash acneiform (63.2 %). Overall, 11 patients (57.9 %) had adverse events leading to a dose reduction, although the safety profile was consistent with that reported in previous studies. CONCLUSION: Our results indicated that vandetanib enabled a prolonged and clinically meaningful PFS and OS in patients with previously treatedRET-rearranged advanced NSCLC at the updated final analysis. The safety profile was consistent with that reported in previous studies, although most of the patients experienced off-target adverse events besides RET.
Authors: Alessandro Russo; Andrés F Cardona; Christian Caglevic; Paolo Manca; Alejandro Ruiz-Patiño; Oscar Arrieta; Christian Rolfo Journal: Transl Lung Cancer Res Date: 2020-12