The efficacy and safety of lenvatinib (LEN) are unknown in cases that were excluded in the phase III trial (REFLECT trial) of LEN, including those who experienced tyrosine kinase inhibitors (TKI) before LEN. In addition, no evidence has been established for early introduction of molecular targeted therapy in BCLC stage B patients. Therefore, we verified the efficacy and safety in the patients who did not meet the inclusion criteria of REFLECT trial and those who were BCLC Stage B.
A total of 203 patients received LEN from March 2018 to January 2019 at 21 sites in Japanese Red Cross Study Liver Group were registered. 128 cases out of REFLECT trial criteria and 74 cases of BCLC Stage B were retrospectively investigated. Tumors assessments in accordance with modified RECIST were done using dynamic CT and/or MRI.
128 of 203 (63%) patients did not meet the inclusion criteria of the REFLECT trial. These cases included 69 receiving TKI therapy before LEN. The ORR and DCR in TKI naïve were 45% and 84%, respectively, and were 29% and 81% in TKI experienced (p = 0.072, p = 0.671). The OS between TKI naïve and experienced patients was not significantly different (p = 0.618), even though baseline albumin level and ALBI score were significantly lower in TKI experienced patients than TKI naïve (p = 0.001 and 0.005). 74 cases of BCLC Stage B included 57 with TACE history, 8 without, and 9 cases unknown. Although there was no difference between two groups in the baseline Child-Pugh score, ALBI score and AFP value, patients with TACE less than 6 times (n = 53) before LEN was significantly better in OS than those with TACE of 6 times or more (n = 12) (p = 0.025).
Also in TKI experienced which was excluded from the REFLECT trial, ORR, DCR and OS did not differ from TKI naïve, and LEN may be useful as TKI 2nd line and 3rd line. In BCLC Stage B patients, TACE group less than 6 times has a better prognosis after LEN treatment compared with group more than 6 times, and an early introduction of LEN for multiple TACE cases may contribute to life prognosis improvement is there.
Clinical trial identification
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All authors have declared no conflicts of interest.