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Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The most common adverse reactions associated with lenvatinib include GI disturbances (e.g., vomiting, diarrhea, nausea, decreased appetite, weight loss, stomatitis, abdominal pain, and gastrointestinal perforation), hypertension, fatigue, arthralgia/myalgia, headache, proteinuria, palmar-plantar erythrodysethesia (PPE) syndrome, and dysphonia.
Gastrointestinal cancer
Published in Peter Hoskin, Peter Ostler, Clinical Oncology, 2020
Sorafenib is a multikinase inhibitor, which decreases cell growth and angiogenesis. It increases median survival to 11 months compared with 8 months for those treated by placebo. The commonest side effects are diarrhoea, hand–foot syndrome and fatigue. Lenvatinib is a newer drug in this class which has slightly higher activity but may cause hypertension.
Systemic Therapy (Targeted Therapy and Immunotherapy) for Thyroid Cancers
Published in Madan Laxman Kapre, Thyroid Surgery, 2020
This MKI targets and also inhibits several targets, namely VEGFR 1–3, FGFR 1–4, PDGFR, RET, and c-kit [27]. It showed promising activity in an initial phase II single arm trial of 58 treatment naïve or re-treated advanced RAI-refractory thyroid cancers [28]. This was followed by a phase III, randomized, placebo-controlled trial (SELECT trial). This trial randomized 261 patients to either receive lenvatinib (24 mg per day in 28-day cycles) or a placebo. There was significantly better PFS in the treatment arm (18.3 months vs. 3.6 months; HR 0.21; p < 0.0001). The response rate was promising at 64%, with four patients achieving complete response. The discontinuation rate due to toxicity was 14% [29]. Subsequently, lenvatinib was approved by the FDA for treatment of advanced RAI-refractory thyroid cancers. Owing to its better efficacy and safety profile, lenvatinib is currently regarded as the first line MKI in treatment of such thyroid cancers [30].
Pembrolizumab plus lenvatinib combination therapy for advanced endometrial carcinoma
Published in Expert Review of Anticancer Therapy, 2023
Christopher A. Walker, Alexandra N. Spirtos, David S. Miller
Although lenvatinib and pembrolizumab appear to be cost-effective, these newer agents can certainly lead to significant financial toxicity to both patients and the health-care system. Financial toxicity is a known problem for patients with gynecologic cancers and is associated with medication noncompliance, significant changes in spending habits, borrowing money, anxiety, and depression [83–85]. Since this combination has been instituted, health-care providers have recognized and addressed ways to reduce unnecessary financial burden on patients. For example, early recognition and appropriately addressing adverse events could lead to less costly medical interventions and hospitalizations. At the SGO 2022 Annual Meeting on Women’s Cancer, a study reported that the manufacturer’s dose-specific packaging of lenvatinib led to a significant overspending [86]. Unfortunately, dose reductions for lenvatinib are relatively common. Due to the dose-specific packaging, dose reductions oftentimes lead to patients requiring a new 30-day pack. Previously, there were restrictions on how often and under what conditions they could switch out the pack for a lower dose with no extra cost. After realizing the extent of overspending, the lenvatinib manufacturer adjusted the dose exchange program to allow for patients to exchange pills when needed at no additional cost.
Lenvatinib plus pembrolizumab combination therapy for adult patients with advanced renal cell carcinoma
Published in Expert Review of Anticancer Therapy, 2022
Lenvatinib is a small-molecule tyrosine kinase inhibitor against multiple targets which play a central role in the activation of signal transduction pathways important for tumor angiogenesis, lymphogenesis, tumor growth and cancer progression [38,43]. VEGF has been identified as a crucial regulator of physiological and pathological angiogenesis pathways and increased expression of VEGF is associated with a poor prognosis in many types of cancers [44]. Lenvatinib main antitumor effect is exerted via tumor angiogenesis by inhibiting the function of the VEGF receptor. Furthermore, the other targets of lenvatinib including, FGFR, RET, PDGFRa, and KIT, are also involved in cancer cells proliferation, thus lenvatinib also has a direct inhibitory effect on cancer cell proliferation [43].
A randomized, open-label, single-dose, two-cycle crossover study to evaluate the bioequivalence and safety of lenvatinib and Lenvima® in Chinese healthy subjects
Published in Expert Opinion on Investigational Drugs, 2022
Zhongnan Xu, Yanli Wang, Guangwen Liu, Jiahui Chen, Wanhua Wang, Yang Cheng, Qing Ren, Yingzi Cui, Wei Yang, Zhengzhi Liu, Xuesong Chen, Jinling Xue, Tianying Chang, Xinyao Qu, Shuang Yu, Yannan Zhou, Kaibo Xu, Zhengjie Su, Qiaohuan Deng, Yicheng Zhao, Haimiao Yang
All subjects were generally in good condition with stable vital signs and no SAE in the trial. AEs that occurred in the trial included increased thyroid-stimulating hormone, headache, dizziness, head congestion, vertigo, nausea, bradycardia, hematuria, fatigue, loss of appetite, hypotension, etc. All AEs returned to normal without treatment. This is consistent with the AEs reported for Lenvima® [5,37–39]. However, the influence of other factors cannot be determined. Other reported AEs were not observed in this study, which may be related to the low medication frequency, low dose and short cycle. Studies have shown that pregnant women taking lenvatinib may cause harm to the fetus [36,40]. Therefore, the subjects took contraceptive measures from 2 weeks before the trial to 3 months after the last medication, and no pregnancy event occurred during the trial.