OA18.03 Real-World Data on the Efficacy and Safety of Lenvatinib in Patients with Previously Treated Thymic Carcinoma
Nobuaki MamesayaKoichi TakagiGota SaitoHiroshi TanakaShoji KuboTakehito ShukuyaRyosuke TsugitomiT. SasakiTomohiro ObaT. YamanakaMotoko TachiharaH. GyotokuHiromi NagashimaM. TamiyaH. KanemuraTakehiro TozukaM. FurutaShingo SakataA. MouriHideto MiwaHiroshi KawachiTakashi NinomiyaYasuo NagaiHitoshi OginoKentaro ItoYoshitaka TamuraTakaaki TokitoMikiko IshiharaTakashi Suzuki
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The phase III REFLECT study utilized bodyweight-based lenvatinib dosing in patients with unresectable hepatocellular carcinoma, based on results of the phase II Study 202. This post hoc analysis compared efficacy and safety in patients with lower and higher bodyweights.This comparison included patients from Study 202 (Japanese, n = 43; Korean, n = 3) and Japanese patients from REFLECT (n = 81) who received lenvatinib. In Study 202, all patients received a starting dose of lenvatinib 12 mg/day; in REFLECT, patients received starting doses based on bodyweight (patients <60 kg, 8 mg/day; ≥60 kg, 12 mg/day). Safety and efficacy were assessed in both studies according to bodyweight.In Study 202, treatment-related, treatment-emergent adverse events (TEAEs) led to dose reductions in 80.8% and 55.0% of patients in the lower and higher bodyweight groups, respectively. In REFLECT, treatment-related TEAEs led to dose reductions in 52.5% and 70.7% of patients in the 8 and 12 mg groups, respectively. In Study 202, median overall survival (OS) was 16.2 months (95% confidence interval [CI], 9.8-25.1) and 21.3 months (95% CI, 10.1-not estimable) in the lower and higher bodyweight groups, respectively. In REFLECT, median OS was 15.8 months (95% CI, 10.4-27.6) and 18.2 months (95% CI, 11.3-26.9) in the 8 and 12 mg groups, respectively.Comparison between patients in Study 202 and REFLECT demonstrates efficacy was maintained with improved safety in patients with lower bodyweights who received lenvatinib 8 mg/day in REFLECT versus patients who received lenvatinib 12 mg/day in Study 202.
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Abstract The purpose of this study was to investigate the relationships among plasma concentrations (C 0 ) of lenvatinib, angiopoietin (Ang)-1 and Ang-2, and clinical responses to lenvatinib therapy in thyroid cancer patients. The median change rates of Ang-1 and Ang-2 at 1 month after treatment from baseline in all patients were − 15.3% and − 48.4%, respectively. However, the change of Ang-1 and Ang-2 at 1 month from baseline did not correlate with lenvatinib C 0 . In patients with partial response (PR) and stable disease to lenvatinib, Ang-2 at 1 month were significantly lower than Ang-2 at baseline ( P < 0.001 and P < 0.05, respectively), but were not significantly lower in patients with progressive disease. The area under the ROC for PR prediction was 0.667, giving the best sensitivity (69.2%) and specificity (73.9%) at a threshold of the change rate of Ang-2 of -49.83%. In patients who continued treatment with lenvatinib for 1 year, Ang-2 at 1 month and 1 year were significantly lower than those at baseline (each P < 0.001). The change of Ang-2 at 1 month after treatment from baseline rather than simply the Ang-2 level at baseline may be important as a biomarker of the inhibitory effect of angiogenesis by lenvatinib.
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Background: In an earlier study, intravenous (i.v.) ibandronate 6 mg administered every 3–4 weeks had a similarly good renal safety profile whether infused over 15 or 60 min in women with breast cancer and bone metastases. This current study focuses on the renal safety of the extended use of ibandronate. Patients and Methods: Patients completing the original study could choose to enter a follow-up phase and continue (or switch) to receive ibandronate 6 mg by 15-min i.v. infusion every 3–4 weeks. The primary endpoint was the percentage of patients with a serum creatinine increase of ≧44.2 mmol/l (= 0.5 mg/dl) from core baseline. Results: Fourteen patients entered the follow-up phase and received a median of 16 infusions (range: 9–24). No patient reached the primary endpoint. Most adverse events were mild to moderate in intensity. None of the 6 reported treatment-related adverse events was considered severe or reported as a serious adverse event. Conclusions: Ibandronate was well tolerated when administered as a 6-mg i.v. infusion over 15 min every 3–4 weeks during the follow-up phase to the earlier core study. No evidence of any treatment-related deterioration in renal function was noted, and no new or unexpected adverse events occurred.
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There is a number of unresolved issues regarding the systemic therapy administration for hepatocellular carcinoma (HCC). Their solution is facilitated by accumulating real‑world study results. Lenvatinib therapy is a recognized drug with a good efficacy and safety profile for the treatment of HCC. Subanalyses of the REFLECT study showed that the absence of stratification by baseline AFP and baseline liver function, as well as the lack of options for subsequent drug therapy after lenvatinib, also affects the outcomes. Once these factors are taken into account, the hypothesis of superiority of lenvatinib to sorafenib and other drugs can be tested. Real‑world clinical studies have demonstrated positive results of lenvatinib therapy in patients with Child‑Pugh class B liver function, provided recommendations on the sequence of systemic therapy after lenvatinib and on the use of lenvatinib in patients with BCLC stage B, along with considering the possibility of lenvatinib monotherapy and the prospects for its use in patients with nHCC. Further real‑world studies of lenvatinib for HCC in the Russian population are required.
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While there is a clear consensus for defining radioiodine-refractory differentiated thyroid cancer (RR-DTC), it is unknown whether these criteria are equally valid for determining when radioiodine (RAI) therapy is no longer beneficial and systemic treatment should be considered. Lenvatinib, a multikinase inhibitor, significantly prolonged progression-free survival (PFS) compared to placebo in a Phase 3 trial in RR-DTC (SELECT; hazard ratio [HR]: 0.21 [99% confidence interval (CI) 0.14-0.31]; p < 0.001). This sub-analysis compared clinical outcomes of lenvatinib-treated patients in SELECT stratified by RR-DTC inclusion criteria.
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Two tyrosine kinase inhibitors, lenvatinib and sorafenib, are available systemic therapies for patients with metastatic differentiated thyroid carcinoma. However, the treatment options for carcinoma refractory to both lenvatinib and sorafenib are limited. Here, we present a case of metastatic papillary thyroid carcinoma that showed resensitization to rechallenge with lenvatinib. A 72-year-old woman who had been diagnosed with papillary thyroid carcinoma with multiple lymph node and lung metastases progressed with the emergence of subcutaneous metastasis after 3 years of response to initial lenvatinib. Five months after switching to sorafenib, the tumor was enlarged with increased contrast enhancement on computed tomography, suggesting progressive disease. Three months after the reintroduction of lenvatinib, marked tumor shrinkage and a decrease in its contrast enhancement were seen. Rechallenge with lenvatinib showed tumor resensitization. Therefore, rechallenge with lenvatinib may be a treatment option in patients who have experienced progressive disease after initial response to lenvatinib and subsequent sorafenib.
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症例は慢性C型肝炎に罹患し飲酒習慣もある60歳代男性で,原発性肝細胞癌の一部に破裂予防の肝動脈塞栓術施行後,lenvatinib 8 mg/日を開始した.約1カ月で腫瘍に感染し,抗生剤治療不応かつ経皮的ドレナージ困難にて,lenvatinibを一週間休薬し,開腹下感染腫瘍切除術を施行した.術後創部治癒に問題なく,lenvatinibを4 mg/日で再開したが,肝障害,倦怠感,食思不振で35日間休薬した.dexamethasone併用して再開し,8 mg/日まで増量したが動脈血流減少せず,lenvatinib血中濃度が低値であった.12 mg/日に増量後,有害事象なしに血中濃度は上昇し,動脈血流も低下した.腫瘍感染の治療困難例は耐術能が許せば,lenvatinibの適切な休薬で外科的治療も選択でき,また,lenvatinib血中濃度による投与量の調整は有効な可能性がある.
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There is no standard posttreatment for patients with advanced hepatocellular carcinoma (HCC) in whom lenvatinib therapy has failed. This study aimed to investigate rates of migration to posttreatment after lenvatinib and to explore candidates for second-line agents in the patients with failed lenvatinib therapy.We retrospectively collected data on patients with advanced HCC who received lenvatinib as the first-line agent in 7 institutions.Overall survival and progression-free survival (PFS) of 178 patients who received lenvatinib as the first-line agent were 13.3 months (95% confidence interval [CI], 11.5-15.2) and 6.7 months (95% CI, 5.6-7.8), respectively. Sixty-nine of 151 patients (45.7%) who discontinued lenvatinib moved on to posttreatment. The migration rates from lenvatinib to the second-line agent and from the second-line agent to the third-line agent were 41.7 and 44.4%, respectively. Based on multivariate analysis, response to lenvatinib (complete or partial response according to modified RECIST) and discontinuation of lenvatinib due to radiological progression, as well as male were associated with a significantly higher probability of migration to posttreatment after lenvatinib. On the other hand, alpha-fetoprotein levels of 400 ng/mL or higher was correlated with a significantly lower probability of migration to posttreatment after lenvatinib. Of 63 patients who received second-line systemic therapy, 53 (84.2%) were administered sorafenib. PFS, objective response rate (ORR), and disease control rate (DCR) for sorafenib treatment were 1.8 months (95% CI, 0.6-3.0), 1.8%, and 20.8%, respectively. According to the Cox regression hazard model, Child-Pugh class B significantly contributed to shorter PFS. PFS, ORR, and DCR of 22 patients who received regorafenib after lenvatinib in any lines were 3.2 months (range, 1.5-4.9 months), 13.6%, and 36.3%, respectively. Similarly, PFS, ORR, and DCR of 17 patients who received regorafenib after lenvatinib in the third-line (after sorafenib) were 3.8 months (range, 1.1-6.5 months), 17.6%, and 41.2%, respectively.Sorafenib may not be a candidate for use as a posttreatment agent after lenvatinib, according to the results of the present study. Regorafenib has the potential to become an appropriate posttreatment agent after lenvatinib.
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