Efficacy Of Anlotinib In Patients Research Articles

Early Structural, Biochemical, and Metabolic Responses to Anlotinib in Patients With Progressive Radioactive Iodine Refractory Differentiated Thyroid Cancer

ObjectiveWe aimed to assess the early efficacy of anlotinib in patients with progressive radioactive iodine refractory differentiated thyroid cancer at the structural, biochemical, and metabolic levels. MethodsTen eligible patients were prospectively enrolled to receive anlotinib. Their responses were assessed at 6 weeks. Apart from the structural response according to Response Evaluation Criteria in Solid Tumors version 1.1, the biochemical response was assessed by serum thyroglobulin (Tg), and the metabolic response was assessed by 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) according to the European Organization for Research and Treatment of Cancer criteria. A safety profile was recorded. ResultsStructurally controlled disease (20% partial response + 80% stable disease) was observed in all patients. The median longest diameter of target lesions shrank from 20.8 mm (IQR, 14.9-27.5) to 17.0 mm (IQR, 14.1-23.7) (P < .001), and the average shrinkage rate was −15.1 ± 14.1%. Sharp serum Tg reduction by 72.8 ± 16.4% was observed in 8 measurable patients. The 18F-FDG PET/CT-mapped glucose metabolic response was not quite comparable to the structural response, with 90% of the patients having controlled disease (30% partial metabolic response + 60% stable metabolic disease), whereas 10% presented progressive metabolic disease. The most common treatment-emergent adverse events (AEs) were hypertension (100%) and proteinuria (70%). Most AEs were grade 1 or 2, whereas grade 3 AEs occurred only in hypertension. ConclusionAnlotinib is generally well tolerated and can bring early disease control within the initial 6 weeks of treatment. The sharp biochemical response suggests Tg to be an early sensitive biomarker to anlotinib, whereas the heterogeneous metabolic response might play a complementary role.

Efficacy of anlotinib for advanced SCLC patients: A real-world study.

e20621 Background: Anlotinib is a novel small molecule multi-target tyrosine kinase inhibitor, which has been approved as a third-line therapy for patients with advanced small cell lung cancer (SCLC) by NMPA in Aug 2019. ALTER 1202 trial has demonstrated that anlotinib significantly prolonged progress-free survival (PFS) and improved disease control rate (DCR) of advanced SCLC patients. Since the efficacy of patients in real clinical practice is affected by many factors, the objective of this study was to assess the efficacy of anlotinib for patients with advanced SCLC in real world. Methods: This is a multi-center, non-interventional, prospective real-world study and all registered data are collected from real clinical practice cases. Patients diagnosed as advanced SCLC and treated with anlotinib were included. The primary endpoint was PFS, and secondary endpoints included overall survival (OS), objective response rate (ORR), DCR and safety. Results: Until Dec 2021, a total of 44 eligible patients were included, with a median age of 62 years, including 34 males (77.3%) and 10 females (22.7%). Among them, 38 patients (86.4%) were diagnosed as a limited stage SCLC and 6 patients (13.6%) diagnosed extensive stage. All patients have not received other targeted therapies before. The median PFS was 6.0 months (95%CI 2.4-5.8), and the median OS was 15.9 months (95%CI 9.1-18.83). At the data cut-off date, 1 patient was assessed as CR, 22 patients were assessed as PR, 15 patients were assessed as SD and 4 patients were assessed as PD. The ORR was 52.3% and the DCR was 86.4%. Conclusions: Significant improvement in OS and PFS were found for advanced SCLC patients in this real-world study. This exhibited that anlotinib has a potential efficacy over previous treatment models. Of course, safety must be further observed subsequently.

The efficacy of anlotinib as third-line treatment for non-small cell lung cancer by EGFR mutation status: a subgroup analysis of the ALTER0303 randomized phase 3 study.

BackgroundAnlotinib demonstrated improved overall survival (OS) and progression-free survival (PFS) compared with placebo as a third-line or subsequent therapy in patients with non-small cell lung cancer (NSCLC) in the ALTER0303 trial. The status of epidermal growth factor receptor (EGFR) mutation, different previous treatment may affect the efficacy of subsequent therapy, and we did this subgroup analysis to characterize the efficacy of anlotinib in patients with and without EGFR mutation.MethodsThe ALTER0303 trial was a randomized, double-blind, phase 3 study of anlotinib in patients with NSCLC who failed at least 2 lines of treatment. In the study, 138 of 437 randomized patients were EGFR mutation positive. A Cox model was used to examine the influence of previous treatment on the efficacy of anlotinib according to EGFR mutation status.ResultsFor patients with EGFR mutation, the OS was 10.7 and 6.3 months (HR 0.59; 95% CI: 0.38–0.94, P=0.025) in the anlotinib and placebo group, respectively. The PFS was 5.6 and 0.8 months (HR 0.21; 95% CI: 0.13–0.32, P<0.0001) in the anlotinib and placebo group, respectively. For patients without EGFR mutation, the OS was 8.9 months for anlotinib and 6.5 months for placebo (HR 0.73; 95% CI: 0.55–0.97, P=0.029), and the PFS was 5.4 months for anlotinib and 1.6 months for placebo (HR 0.29; 95% CI: 0.22–0.39, P<0.0001). In the anlotinib group, the OS and PFS for patients with and without EGFR mutation was 10.7 and 8.9 months (HR 0.69; 95% CI: 0.50–0.95, P=0.021), 5.6 and 5.4 months (HR 1.00; 95% CI: 0.75–1.34, P=1.000), respectively. The incidence of adverse events was similar in subgroups.ConclusionsThis analysis demonstrated that the benefit of anlotinib as a third-line therapy for patients with NSCLC was independent of EGFR mutation status.

The real-world clinical outcomes and treatment patterns of patients with unresectable locally advanced or metastatic soft tissue sarcoma treated with anlotinib in the post-ALTER0203 trial era.

BackgroundThe ALTER0203 clinical trial showed that anlotinib, a multitargeted tyrosine kinase inhibitor, had antitumor effects on advanced soft tissue sarcoma (STS) after the failure of standard chemotherapy. We aimed to evaluate the real‐world efficacy and explore prognostic factors and treatment patterns of anlotinib in patients with advanced STS.MethodsWe retrospectively analyzed the data of patients with unresectable locally advanced or metastatic STS who received at least one dose of anlotinib from June 2018 to March 2021. The survival data were analyzed using the Kaplan–Meier method and compared using the log‐rank test. The Cox proportional hazards model was performed for multivariate analysis.ResultsA total of 209 patients were included. The median age was 48 (range 11–85) years. The median follow‐up, progression‐free survival, and overall survival were 18.7 months, 6.1 months [95% confidence interval (CI): 4.9–7.2], and 16.4 months (95% CI: 13.6–19.1), respectively. The objective response rate was 13.4%. Nutritional status, Eastern Cooperative Oncology Group (ECOG) performance status, and anlotinib treatment patterns (combination therapy or switch maintenance therapy vs. monotherapy) were significantly associated with progression‐free survival. Besides, pathological grade, nutritional status, ECOG performance status, and anlotinib treatment patterns were predictive of overall survival. Due to anlotinib‐related toxicity, 31 (14.8%) patients, and 25 (12.0%) patients experienced dose reduction and treatment discontinuation, respectively.ConclusionThese findings confirmed the efficacy of anlotinib in patients with advanced STS in a real‐world setting. The patterns of anlotinib treatment deserve further exploration.

A Retrospective Analysis of the Effect of Anlotinib in Patients With Lung Cancer With or Without Previous Antiangiogenic Therapy.

ObjectiveThe purpose of this study was to initially investigate the effect of previous antiangiogenic therapy (bevacizumab and endostatin) on the efficacy of anlotinib in patients with advanced or metastatic lung cancer (LC).MethodsWe retrospectively collected the clinical data of patients with LC treated with anlotinib and divided them into group A (treated with anlotinib after the failure of previous antiangiogenic drugs and group B (no prior use of antiangiogenic drugs). We used propensity score matching (PSM) for confounding factors between the groups. Progression-free survival (PFS) and overall survival (OS) were also recorded.ResultsA total of 160 patients were included in the analysis. The median OS in groups A and group B was 11.8 months and 16.1 months (P=0.120), whereas the median PFS was 3.1 months and 4.7 months (P=0.009), respectively. Moreover, the objective response rate (ORR) of the two groups was 9.6% and 10.4% (P=0.874), and the disease control rate (DCR) was 71.1% and 80.5% (P=0.165).After PSM (n=46), baseline characteristics were comparable between groups A and B. Furthermore, the median OS of the two groups was 14.6 months and 16.2 months (P=0.320), whereas the median PFS was 3.5 months and 4.5 months (P=0.040), respectively. Moreover, the ORR of the two groups were 13.0% and 10.9% (P=0.748), and the DCR were 78.3% and 82.6% (P=0.599), respectively.ConclusionsPrevious antiangiogenic treatments may affect the PFS of patients who receive anlotinib later, but it might not affect the patient’s ORR and OS.

Anlotinib, a multitarget tyrosine kinase inhibitor, for advanced lung cancer patients: Efficacy in real-world study.

e15652 Background: Anlotinib is an novel small molecule multi-target tyrosine kinase inhibitor, which has been approved as a third-line therapy for patients with advanced NSCLC by CFDA in May 2018, and also approved as third-line therapy for patients with advanced SCLC in China in 2019. The objective of this study was to assess the efficacy of Anlotinib for patients with advanced lung cancer in the real world. Methods: We reviewed the patients who were diagnosed as advanced lung cancer and had received anlotinib in Jiangsu Caner Hospital from May 2018 to Sep 2019. The primary endpoint was progression-free survival (PFS) and the secondary endpoint was objective response rate (ORR), disease control rate (DCR) and safety. Results: A total of 465 patients were included in our study, containing 384 cases of NSCLC and 81 cases of SCLC. Among patients with NSCLC, 85 cases received anlotinib alone or anlotinib based therapy as first-line and second-line treatment, whereas 299 cases received anlotinib alone or anlotinib based therapy as third-line or later treatment. There were no significant differences in PFS, ORR and DCR between cohort of 1st /2nd line treatment and those with 3rd /later treatment. However, patients received combination therapy (including anlotinib combined with PD1 inhibitors such as Nivolumab, pembrolizumab, or chemotherapy such as platinum, docetaxel, pemetrexed, paclitaxel, tegafur, etc.) showed a significant longer PFS and higher ORR and DCR (P &lt; 0.001, table). In patients with SCLC, 44 cases received anlotinib alone or anlotinib based therapy as first-line and second-line treatment. There were no significant differences in PFS, ORR and DCR between cohort of anlotinib monotherapy and other combination therapies (P &gt; 0.05, table). No additional safety profile was observed. Conclusions: Anlotinib shows similar effect in patients with NSCLC and SCLC in real world. Anlotinib provides more significant benefits when combining with PD1 inhibitor or chemotherapy comparing with monotherapy in patients with advanced NSCLC. [Table: see text]

Anlotinib in patients with recurrent platinum-resistant or refractory ovarian carcinoma: A prospective, single-arm, single-center, phase II clinical study.

6061 Background: Recurrent platinum-resistant or refractory ovarian carcinoma is difficult to treat, and how to improve the treatment effect of these patients is still an urgent problem to solve. Anlotinib is a new multi-target tyrosine kinase inhibitor and its anti-tumor vascular targets include VEGFR, PDGFR and FGFR. Previous researches have shown clinical antitumor activity of anlotinib in various cancers, including the phase I study on gynecologic tumor. This phase II study (ChiCTR2000029654) aims to further evaluate the safety and efficacy of anlotinib in patients with recurrent or refractory ovarian carcinoma. Methods: Patients who have previously received second-line or more chemotherapy, with histopathologically confirmed ovarian high-grade serous gonadal carcinoma (including salpingocarcinoma and peritoneal carcinoma), ECOG 0-2 were considered eligible for enrollment. Anlotinib was administered orally (12 mg qd, d1-14; 21 days per cycle) till disease progression, death or intolerant toxicity. Therapeutic effects are evaluated every 6 weeks. The primary endpoint was objective response rate (ORR) and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety and quality of life (QOL). Results: Between 2019 March to 2020 January, 15 patients (female) with FIGO histopathological stage IA(6.7%), IIIA (73.3%), IIIC (6.7%) and IV (13.3%) were enrolled and 14 patients were evaluable with a median age of 59 years (range: 47-69). The mean follow-up period is 3.5 months (95% CI: 2.1-4.8). Therapeutic evaluation showed the incidence of partial response, stable disease and progression disease was 14.3%, 57.1% and 28.6% respectively, yielding the ORR of 14.3% (2/14; 95% CI: 1.8%-42.8%) and the DCR of 71.4% (10/14; 95% CI: 41.9%-91.6%). The median PFS was not reached. Most of the occurring AEs were grade 1, including hypertention (57.1%), fatigue (50.0%), hand-foot syndrome (35.7%), hoarseness (14.3%), diarrhea (7.1%), gum-pain (7.1%), decrease in leukocyte count (6.7%) and urine protein (7.1%). Only cancer pain (7.1%) was grade 2. No high grade AE was observed in these 14 patients. Neither unexpected safety signals nor treatment related death occurred. Conclusions: Anlotinib showed a promising efficacy with a favourable toxicity profile for patients with recurrent platinum-resistant or refractory ovarian carcinoma. And we will report more results ahout anlotinib in the future. Clinical trial information: ChiCTR2000029654.

P3.03-006 Efficiency of Anlotinib as 3rd Line Treatment in Patients with Different EGFR Gene Status, an Exploratory Subgroup Analysis of ALTER0303 Trial

Anlotinib hydrochloride is a novel TKI targeting the VEGFR, FGFR, PDGFR and c-Kit. ALTER0303 trial (NCT02388919), phase III study has demonstrated that Anlotinib significantly prolonged OS and PFS in advanced NSCLC patients as 3rd line treatment. Here we report the efficacy of anlotinib in patients with or without EGFR gene mutations from the ALTER0303 trial.