scholarly journals Pilot Dose Comparison of Apatinib in Chinese Patients With Progressive Radioiodine-Refractory Differentiated Thyroid Cancer

2018 ◽  
Vol 103 (10) ◽  
pp. 3640-3646 ◽  
Author(s):  
Xin Zhang ◽  
Chen Wang ◽  
Yansong Lin
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Objective Response ◽  
Lesion Size ◽  
Target Lesion ◽  
Chinese Patients ◽  
Efficacy And Safety ◽  
Dose Comparison ◽  
Thyroglobulin Level ◽  
Grade 3

Abstract Context Apatinib has shown overwhelming efficacy in progressive radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) starting at a 750-mg dosing protocol; however, a relatively high incidence of treatment-associated adverse events (TAAEs) was observed, which reduced quality of life and interrupted the treatment. Objectives To evaluate the efficacy and safety of apatinib with two different dosing schedules [750 or 500 mg once a day (q.d.)] in RAIR-DTC. Participants and Methods Twenty patients were sequentially recruited to receive apatinib beginning at 750 (n = 10) or 500 (n = 10) mg q.d. Efficacy and safety were compared in each 28-day cycle at the beginning two cycles and every two cycles thereafter. Results After six treatment cycles, the best disease control rates were 100% for the 750- and 500-mg schedules, respectively, and the best objective response rates were 90.0% and 70.0% (P = 0.58), respectively. The two dosing schedules did not differ regarding greatest reduction in target lesion size (−42.7% vs −40.5% for the 750- vs 500-mg schedule, P = 0.48) and thyroglobulin level (−82.5% vs −94.3% for the 750- vs 500-mg schedule, P = 0.14). All patients experienced TAAEs, and the two dosing schedules showed similar incidence in TAAEs of grade ≥3 (100% vs 70% for 750 vs 500 mg, P = 0.21). However, the frequency of TAAEs was much higher in the 750-mg schedule (26.8 ± 6.5 vs 18.1 ± 6.5 in any grades, P = 0.01; 5.2 ± 3.0 vs 1.6 ± 1.3 in grade ≥3, P < 0.01). Conclusion Within six cycles of follow-up, the 500-mg starting dose protocol might be less toxic than the 750-mg protocol, whereas the efficacy was similar between the two dosages.

Effect of Age on the Efficacy and Safety of Lenvatinib in Radioiodine-Refractory Differentiated Thyroid Cancer in the Phase III SELECT Trial

2017 ◽  
Vol 35 (23) ◽  
pp. 2692-2699 ◽  
Author(s):  
Marcia S. Brose ◽  
Francis P. Worden ◽  
Kate L. Newbold ◽  
Matthew Guo ◽  
Arti Hurria
Keyword(s):  
Thyroid Cancer ◽  
Older Patients ◽  
Differentiated Thyroid Cancer ◽  
Objective Response ◽  
Age Groups ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Effect Of Age

Purpose In the Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT), lenvatinib significantly prolonged progression-free survival (PFS) versus placebo in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). This prespecified subanalysis investigated the effect of age on the efficacy and safety of lenvatinib. Patients and Methods This randomized, double-blind, phase III study enrolled patients with histologically confirmed RR-DTC stratified by age (≤ 65 or > 65 years). Patients (N = 392) received lenvatinib 24 mg/day (n = 261) or placebo (n = 131). The primary end point was PFS; secondary end points included overall survival (OS), objective response rate, and safety. Results In both treatment arms, median ages were 56 (younger group) and 71 years (older group). PFS benefit was maintained with lenvatinib versus placebo in the younger and older age groups, with median PFS of 20.2 versus 3.2 months (hazard ratio [HR], 0.19; 95% CI, 0.13 to 0.27; P < .001) and 16.7 versus 3.7 months (HR, 0.27; 95% CI, 0.17 to 0.43; P < .001), respectively. PFS did not differ with age in either treatment arm. OS was improved in older lenvatinib-treated patients versus placebo (HR, 0.53; 95% CI, 0.31 to 0.91; P = .020). Younger lenvatinib-treated patients showed significantly higher ORR (72% v 55%; P = .0038), longer time to first dose reduction (3.7 v 1.5 months), and lower proportion of grade ≥ 3 treatment-related adverse events (67% v 89%; P < .001) compared with older patients. Conclusion This subanalysis demonstrated improved PFS with lenvatinib treatment versus placebo in both age groups, although higher toxicity was observed in older patients. Despite the allowance of crossover after disease progression, the OS benefit was observed in older patients, suggesting that lenvatinib should be considered for treatment of patients of any age with RR-DTC.

scholarly journals Cabozantinib As Salvage Therapy for Patients With Tyrosine Kinase Inhibitor–Refractory Differentiated Thyroid Cancer: Results of a Multicenter Phase II International Thyroid Oncology Group Trial

2017 ◽  
Vol 35 (29) ◽  
pp. 3315-3321 ◽  
Author(s):  
Maria E. Cabanillas ◽  
Jonas A. de Souza ◽  
Susan Geyer ◽  
Lori J. Wirth ◽  
Michael E. Menefee ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Phase Ii ◽  
Differentiated Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Multikinase Inhibitor

Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib. Patients and Methods Patients with RAI-refractory disease with Response Evaluation Criteria in Solid Tumor (RECIST) measurable disease and evidence of progression on prior VEGFR-targeted therapy were enrolled in this single-arm phase II study. The cabozantinib starting dose was 60 mg/day orally but could be escalated to 80 mg if the patient did not experience a response. Patients underwent tumor assessment according to RECIST v1.1 every 8 weeks. In this study, if at least five of 25 response-evaluable patients had an objective response, cabozantinib would be considered a promising agent in this patient population. Results Twenty-five patients were enrolled. The median age was 64 years, and 64% of patients were men. Twenty-one patients had received only one prior VEGFR-targeted therapy (sorafenib, pazopanib, or cediranib), and four patients had received two such therapies. The most common treatment-related adverse events were fatigue, weight loss, diarrhea, palmar-plantar erythrodysesthesia, and hypertension. One drug-related death was noted. Of the 25 patients, 10 (40%) had a partial response, 13 (52%) had stable disease, and two (8%) had nonevaluable disease. The median progression-free survival and overall survival were 12.7 months and 34.7 months, respectively. Conclusion Cabozantinib demonstrated clinically significant, durable objective response activity in patients with RAI-refractory DTC who experienced disease progression while taking prior VEGFR-targeted therapy.

Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after prior VEGFR-targeted therapy: Results from the phase 3 COSMIC-311 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6001-6001
Author(s):  
Marcia S. Brose ◽  
Bruce Robinson ◽  
Steven I. Sherman ◽  
Barbara Jarzab ◽  
Chia-Chi Lin ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Disease Progression ◽  
Differentiated Thyroid Cancer ◽  
Statistical Significance ◽  
Phase 1 ◽  
Objective Response ◽  
Standard Of Care ◽  
Clinical Activity ◽  
Phase 3

6001 Background: Cabozantinib (C), an inhibitor of VEGFR2, MET, AXL, and RET, showed clinical activity in patients (pts) with radioiodine (RAI)-refractory differentiated thyroid cancer (DTC) in phase 1/2 studies (Cabanillas 2017; Brose 2018). This phase 3 study (NCT03690388) evaluated the efficacy and safety of C vs placebo (P) in pts with RAI-refractory DTC who had progressed during/after prior VEGFR-targeted therapy for whom there is no standard of care. Methods: In this double-blind, phase 3 trial, pts were randomized 2:1 to receive C (60 mg QD) or P, stratified by prior lenvatinib treatment (L; yes, no) and age (≤65, > 65 yr). Pts with RAI-refractory DTC must have received L or sorafenib for DTC and progressed during or following treatment with ≤ 2 prior VEGFR inhibitors. Pts randomized to P could cross over to open-label C upon disease progression per blinded independent radiology committee (BIRC). The primary endpoints were objective response rate (ORR) in the first 100 randomized pts and progression-free survival (PFS) in all randomized pts. PFS and ORR were assessed by BIRC per RECIST v1.1. The study was designed to detect an ORR for C vs P (2-sided α = 0.01) and a hazard ratio (HR) for PFS of 0.61 (90% power, 2-sided α = 0.04). A prespecified interim PFS analysis was planned for the ITT population at the time of the primary ORR analysis. Results: As of 19 Aug 2020,125 vs 62 pts had been randomized to the C and P arms, respectively; median age was 66 yr, 55% were female and 63% received prior L. Median (m) follow-up was 6.2 months (mo). At the planned interim analysis, the trial met the primary endpoint of PFS with C demonstrating significant improvement over P (HR 0.22, 96% CI 0.13–0.36; p < 0.0001). mPFS was not reached for C vs 1.9 mo for P; PFS benefit was observed in all prespecified subgroups including prior L (yes, HR 0.26; no, HR 0.11) and age (≤65 yr, HR 0.16; > 65 yr, HR 0.31). ORR was 15% for C vs 0% for P (p = 0.0281) but did not meet the prespecified criteria for statistical significance (p < 0.01). A favorable OS trend was observed for C vs P (HR 0.54, 95% CI 0.27–1.11). Treatment-emergent adverse events (AEs) of any grade with higher occurrences in the C vs P arm included diarrhea (51% vs 3%), hand-foot skin reaction (46% vs 0%), hypertension (28% vs 5%), fatigue (27% vs 8%), and nausea (24% vs 2%); grade 3/4 AEs were experienced by 57% of pts with C vs 26% with P. Dose reductions due to any grade AEs occurred in 57% of pts with C vs 5% with P. Treatment discontinuations due to AEs not related to disease progression occurred in 5% of pts with C vs 0% with P. No treatment-related deaths occurred in either arm. Conclusions: C showed a clinically and statistically significant improvement in PFS over P in pts with RAI-refractory DTC after prior VEGFR-targeted therapy with no unexpected toxicities. C may represent a new standard of care in pts with previously treated DTC. Clinical trial information: NCT03690388.

The efficacy and safety of anlotinib in refractory/recurrent/advanced pediatric solid tumors: A retrospective study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11556-11556
Author(s):  
Suying Lu ◽  
Ye Hong ◽  
Huimou Chen ◽  
Liuhong Wu ◽  
Jia Zhu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Effective Treatment ◽  
Solid Tumors ◽  
Objective Response ◽  
Cancer Center ◽  
Treatment Schedule ◽  
Efficacy And Safety ◽  
Pediatric Solid Tumors ◽  
Hand Foot Syndrome ◽  
Grade 3

11556 Background: Refractory and recurrent advanced pediatric solid tumors are short of effective treatment and with a dismal outcome, thus an urgent need for novel and effective treatment. The aim of the study is to evaluate the efficacy and safety of anlotinib, a novel and oral multi-target receptor tyrosine kinase inhibitor, in refractory or recurrent advanced pediatric solid tumors. Methods: The retrospective, single-institutional, observed study was conducted in Sun Yat-sen University cancer center in China. Refractory, recurrent, or advanced pediatric solid tumors patients treated with anlotinib between 2018 to 2020 were evaluated. Results: Forty-one patients and thirty patients were enrolled in the study to evaluated efficacy and safety, respectively. The objective response ratio (ORR) was 12.2% (95%CI 1.7-22.7): complete response (n = 0) and partial response (n = 5) (Table). The disease control rate (DCR) was 65.9% (95%CI 50.7-81). The median progression-free survival (PFS) was 2.87 months (95%CI 0.86-4.88). According to anlotinib treatment schedule, all patients were divided into three groups: anlotinib monotherapy (A, n = 16), anlotinib combined with immune checkpoint inhibitor treatment (A + ICI, n = 6), anlotinib combined with salvage chemotherapy (A + SC, n = 19). The ORR, DCR and median PFS for three groups were 6.3% (95%CI 7.1-19.6), 56.3% (95%CI 28.9-83.6), 2.43months, 16.7% (95%CI 26.2-59.5), 66.7% (95%CI 12.5-120.9), 1.13months, 15.8% (95%CI 2.3-33.8), 73.7% (95%CI 51.9-95.5), 2.87months, respectively. There was no significantly difference between three groups in aforementioned response index. The incidence rates of any grade and grade 3-4 adverse events were 80% and 20%, respectively. Bleeding (20%), hand-foot syndrome (13.3%), and diarrhea (13.3%) were the most common adverse events. Grade 3-4 adverse events include hypertension, hand-foot syndrome, diarrhea, anemia, and thrombocytopenia. There was no adverse events-related death. Conclusions: For heavily pretreated pediatric solid tumors, anlotinib may be an effective treatment with tolerable adverse events. Further prospective randomized controlled clinical study is warranted.[Table: see text]

Selpercatinib efficacy and safety in patients with RET-altered thyroid cancer: A clinical trial update.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6073-6073
Author(s):  
Eric Jeffrey Sherman ◽  
Lori J. Wirth ◽  
Manisha H. Shah ◽  
Maria E. Cabanillas ◽  
Bruce Robinson ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Thyroid Cancer ◽  
Adverse Events ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Integrated Analysis ◽  
Low Grade ◽  
Efficacy And Safety ◽  
Thyroid Cancers ◽  
Altered Thyroid

6073 Background: Selpercatinib, is a first-in-class, highly selective, CNS active and potent RET inhibitor approved in multiple countries for treatment of RET-fusion positive lung or thyroid cancers. Reported is an update of efficacy and safety results in RET-altered thyroid cancer, with a longer follow up (30 Mar 2020 data cutoff vs 16 Dec 2019) and additional enrolment. Methods: Patients (pts) with RET-mutant medullary thyroid cancer (MTC) and RET-fusion positive thyroid cancer (TC) were enrolled in the global (16 countries, 89 sites) Phase 1/2 LIBRETTO-001 trial (NCT03157128). The primary endpoint was objective response rate (ORR) per RECIST 1.1 by independent review committee (IRC). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), clinical benefit rate (CBR; CR+PR+SD ≥16 weeks), and safety. The integrated analysis set (IAS, n = 143) includes efficacy evaluable MTC pts previously treated with cabozantinib and/or vandetanib (cabo/vande). The primary analysis set (PAS), a subset of IAS, is the first 55 enrolled pts. Cabo/vande naïve MTC pts (N = 112) and TC pts with prior systemic treatment (N = 22) were also analyzed. Safety population includes all pts who received ≥1 dose of selpercatinib (MTC N = 315; TC N = 42) by data cutoff. Results: For MTC patients, the ORR for IAS was 69.2%, in the PAS it was 69.1%, and 71.4% for cabo/vande naïve MTC pts. The ORR for TC pts (n = 22) was 77.3% (see table). Most treatment-emergent adverse events (TEAEs) were low grade; the most common (≥25% of MTC and/or TC pts treated with selpercatinib) were dry mouth, diarrhea, hypertension, fatigue and constipation for both MTC and TC pts, increased ALT/AST, peripheral edema and headache in MTC pts and nausea in TC pts. 4.8% of MTC and TC pts discontinued selpercatinib due to TEAEs but only 1.9% with MTC and none with TC discontinued due to treatment-related adverse events. Conclusions: In this updated analysis, selpercatinib continued to show marked and durable antitumor activity in pts with RET-altered thyroid cancers. Selpercatinib was well tolerated and no new safety concerns were identified. A global, randomized, phase 3 trial (LIBRETTO-531) evaluating selpercatinib compared to cabo/vande in kinase inhibitor naïve MTC pts is ongoing. Clinical trial information: NCT03157128. [Table: see text]

Prognostic Value of Lymphocyte-to-Monocyte Ratio for Japanese Patients With Differentiated Thyroid Cancer Treated With Sorafenib Therapy

2021 ◽  
Vol 1 (5) ◽  
pp. 491-498
Author(s):  
SHOGO NAKAMOTO ◽  
MASAHIKO IKEDA ◽  
SHINICHIRO KUBO ◽  
MARI YAMAMOTO ◽  
TETSUMASA YAMASHITA ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Prognostic Value ◽  
Differentiated Thyroid Cancer ◽  
Median Overall Survival ◽  
Japanese Patients ◽  
Efficacy And Safety ◽  
Systemic Immunity ◽  
Lymphocyte To Monocyte Ratio ◽  
Cell Counts ◽  
Sorafenib Therapy

Background/Aim: We investigated the efficacy and safety of sorafenib in Japanese patients and the prognostic value of systemic immunity markers for predicting clinical outcomes after sorafenib therapy in patients with radioiodine refractory differentiated thyroid cancer (RR-DTC). Patients and Methods: We retrospectively evaluated 26 patients with RR-DTC who underwent sorafenib therapy between July 2014 and December 2020. The systemic immunity markers were calculated from blood cell counts. Results: The median overall survival (OS) was 2,002 days, and the clinical benefit rate was 80.8%. The high lymphocyte-to-monocyte ratio (LMR) group had significantly longer OS than the low LMR group (hazard ratio=0.21; 95% confidence interval=005-0.88; log-rank p=0.019). Adverse events observed in this study were acceptable, and no new safety signals associated with sorafenib were found. Conclusion: Sorafenib therapy is efficacious and safe for Japanese patients with RR-DTC, and baseline LMR may be useful as a sorafenib therapy prognostic marker.

The efficacy and safety of anlotinib in neoadjuvant treatment in locally advanced thyroid cancer: A single-arm phase II clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6069-6069
Author(s):  
Naisi Huang ◽  
Guohua Sun ◽  
Yulong Wang ◽  
Jiaying Chen ◽  
Qing Guan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Thyroid Cancer ◽  
Adverse Events ◽  
Objective Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Primary Treatment ◽  
Tumor Diameter ◽  
Efficacy And Safety ◽  
Advanced Thyroid Cancer

6069 Background: Surgery is the primary treatment for locally advanced thyroid cancer (TC). For some locally advanced TC, R0/R1 resection could not be achieved at initial diagnosis and neoadjuvant treatment would be an option. However, there is still little evidence regarding neoadjuvant treatment in locally advanced TC. Methods: This single-arm, phase 2 study investigated the efficacy and safety of Anlotinib (12mg orally daily, for two weeks on/on week off) for 2-6 cycles in patients with locally advanced TC in the neoadjuvant setting. Operable patients received surgery after neoadjuvant treatment. The primary endpoint was objective response rate (ORR). Results: A total of 13 patients were included and received an average of 3.5 cycles (range: 3-6 cycles) of Anlotinib treatment. 12 cases were papillary thyroid cancer, and 1 was follicular thyroid cancer. The ORR of Anlotinib was 76.9% with 10 partial response (PR), 2 stable disease (SD), and 1 progressive disease (PD). 8 PR and 1 SD patients received surgery after neoadjuvant treatment, of whom 8 had R0/1 resections and 1 had R2 resection. 2 PR patients refused to have surgery and the rest 2 patients were not operable. The R0/1 resection rate for intent to treat population was 61.5% and for per-protocol population was 72.7%. The maximum reduction in sum of tumor diameter was an average of 34.8% (range: 30.9%-45.5%) for PR patients. Most adverse events were grade 1 or 2. Common adverse events of all grade were hypertension (76.9%), hypertriglyceridemia (69.2%), proteinuria (53.8%), TSH increase (53.8%), cholesterol elevation (53.8%) and hand-foot syndrome (38.5%). The majority of adverse events discontinued after the neoadjuvant treatment stopped. Conclusions: Anlotinib demonstrated antitumor activity in the neoadjuvant treatment in locally advanced TC and the majority of patients achieved R0/1 resection. Adverse events were consistent with the known Anlotinib adverse event profile. These results suggest that Anlotinib neoadjuvant treatment represents a new option for locally advanced TC. Clinical trial information: NCT04309136.

Efficacy and Safety of Ixabepilone (BMS-247550) in a Phase II Study of Patients With Advanced Breast Cancer Resistant to an Anthracycline, a Taxane, and Capecitabine

2007 ◽  
Vol 25 (23) ◽  
pp. 3407-3414 ◽  
Author(s):  
Edith A. Perez ◽  
Guillermo Lerzo ◽  
Xavier Pivot ◽  
Eva Thomas ◽  
Linda Vahdat ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Efficacy And Safety ◽  
Peripheral Sensory Neuropathy ◽  
Metastatic Setting ◽  
Grade 3 ◽  
Peripheral Sensory

PurposeTo evaluate the efficacy and safety of ixabepilone in patients with metastatic breast cancer (MBC) resistant to anthracycline, taxane, and capecitabine, in this multicenter, phase II study.Patients and MethodsPatients with measurable disease who had tumor progression while receiving prior anthracycline, taxane, and capecitabine were enrolled. Ixabepilone 40 mg/m2monotherapy was administered as a 3-hour intravenous infusion on day 1 of a 21-day cycle. The primary end point was objective response rate (ORR), assessed by an independent radiology facility (IRF).ResultsA total of 126 patients were treated and 113 were assessable for response. Patients were heavily pretreated: 88% had received at least two lines of prior chemotherapy in the metastatic setting. IRF-assessed ORR was 11.5% (95% CI, 6.3% to 18.9%) for response-assessable patients. Investigator-assessed ORR for all treated patients was 18.3% (95% CI, 11.9% to 26.1%). Fifty percent of patients achieved stable disease (SD); 14.3% achieved SD ≥ 6 months. Median duration of response and progression-free survival were 5.7 and 3.1 months, respectively. Median overall survival was 8.6 months. Patients received a median of 4.0 treatment cycles (range, one to 16 cycles), and 25% of patients received ≥ eight cycles. Grade 3/4 treatment-related events included peripheral sensory neuropathy (14%), fatigue/asthenia (13%), myalgia (8%), and stomatitis/mucositis (6%). Resolution of grade 3/4 peripheral sensory neuropathy occurred after a median period of 5.4 weeks.ConclusionIxabepilone demonstrated clear activity and a manageable safety profile in patients with MBC resistant to anthracycline, taxane, and capecitabine. Responses were durable and notable in patients who had not previously responded to multiple prior therapies.

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