Management of anlotinib‐related adverse events in patients with advanced non‐small cell lung cancer: Experiences in ALTER‐0303

Abstract

Background Anlotinib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet‐derived growth factor receptor, and stem cell factor receptor (c‐Kit). In the phase III ALTER‐0303 trial (Clinical Trial Registry ID: NCT 02388919), anlotinib significantly improved overall survival versus placebo in advanced non‐small cell lung cancer patients who had received at least two previous chemotherapy and epidermal growth factor receptor/anaplastic lymphoma kinase targeted therapy regimens. This study summarized adverse event management in this trial. Methods Patients were randomized (2:1) to anlotinib or placebo up to progression or intolerable toxicity. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and managed by investigators. Key strategies for preventing and managing the most common adverse events included patient education, supportive care, and dose modification. Results Between February 2015 and August 2016, 294 patients received anlotinib. A total of 170 (57.8%) patients received antihypertensive medications for hypertension, 53 (18.0%) patients received levothyroxine for hypothyroidism, 24 (8.2%) patients received fibrates for hypertriglyceridemia, 11 (3.7%) patients took cortisone cream for hand‐foot syndrome, and 38 (12.9%) patients received anti‐diarrheal medications for diarrhea. Dose reduction and drug discontinuation were required in 24 (8.16%) and 31 (10.54%) patients in the anlotinib group, respectively. Conclusion Anlotinb‐related adverse events could be controlled by patient education, prophylactic measures, early and active intervention, and dose modification.

Anlotinib as a molecular targeted therapy for tumors (Review)

“…First, blood pressure (BP) assessment is required for patients who are normotensive or hypertensive, and BP should be controlled before treatment is initiated (76,77). Frequent monitoring of BP during the first few months (weekly during the first cycle and subsequently every 2 to 3 weeks) is important for early intervention and the resolution of hypertension.…”

“…In addition, anti-hypertensive drugs (76,78), such as thiazide-type diuretics, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta blockers and calcium channel blockers (CCBs), are all suitable choices for patients who develop hypertension during treatment. These drugs may be used alone or in combination, but the combination of ACEIs and ARBs is not recommended.…”

Clinical analysis of ECOG PS and adverse reactions in patients with anlotinib at advanced NSCLC as the third or further line treatment: a retrospective observational study

“…Most advanced NSCLC patients inevitably have disease progression after rst-line and second-line treatment, and need further treatment. A Phase III clinical study (ALTER-0303) [15] showed that The median OS(9.63 vs 6.3 months,P = 0.0018), PFS 5.37vs1.4 months P < 0.0001 , DCR 81.0% vs 37.1% P < 0.0001 and ORR 9% vs 1% P < 0.0001 of anlotinib were signi cantly better than those of placebo group, and the adverse reactions were generally tolerable, similar to those reported in previous studies.…”

“…Many studies have further identi ed that anlotinib has broader and more effective anti-tumor effects in vivo than Sunitinib and Sorafenib [11][12]13] . Moreover, pre-Phase II and Phase III clinical studies had preliminarily validated the e cacy and safety of anlotinib in the treatment of advanced NSCLC [14][15] .…”

<p>miR-596 suppresses the expression of Survivin and enhances the sensitivity of osteosarcoma cells to the molecular targeting agent anlotinib</p>

“…5 Anlotinib is an orally available, highly potent multitargeting protein-kinase inhibitor that could block the activation of some receptor tyrosine protein kinase (RTKs), eg, VEGFR2 (vascular endothelial growth factor receptor 2), platelet-derived growth factor receptors α/β (PDGFR α/β), Ret, c-Kit, c-FMS, or discoidin domain receptor 1 (DDR1). 6,7 It has been reported that anlotinib revealed an antitumor effect when used in clinical trials in a variety of human solid tumors, for example nonsmall-cell lung cancer (NSCLC), hepatocarcinoma (HCC), gastric cancer, renal carcinoma (RC), or soft tissue sarcoma. [8][9][10] In 2018, anlotinib was approved by the China Food and Drug Administration (CFDA) for the clinical application of NSCLC treatment.…”