Docetaxel As Monotherapy or Combined With Ramucirumab or Icrucumab in Second-Line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma: An Open-Label, Three-Arm, Randomized Controlled Phase II Trial

2016 ◽  
Vol 34 (13) ◽  
pp. 1500-1509 ◽  
Author(s):  
Daniel P. Petrylak ◽  
Scott T. Tagawa ◽  
Manish Kohli ◽  
Andrea Eisen ◽  
Christina Canil ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Urothelial Carcinoma ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Line Treatment ◽  
Second Line ◽  
Metastatic Urothelial Carcinoma ◽  
Endothelial Growth Factor

Purpose This trial assessed the efficacy and safety of docetaxel monotherapy or docetaxel in combination with ramucirumab (vascular endothelial growth factor receptor 2 antibody) or icrucumab (vascular endothelial growth factor receptor 1 antibody) after progression during or within 12 months of platinum-based regimens for patients with locally advanced or metastatic urothelial carcinoma. Patients and Methods Patients were randomly assigned (1:1:1) to receive docetaxel 75 mg/m2 intravenously (IV) on day 1 of a 3-week cycle (arm A), docetaxel 75 mg/m2 IV plus ramucirumab 10 mg/kg IV on day 1 of a 3-week cycle (arm B), or docetaxel 75 mg/m2 IV on day 1 plus icrucumab 12 mg/kg IV on days 1 and 8 of a 3-week cycle (arm C). Treatment continued until disease progression or unacceptable toxicity. The primary end point was investigator-assessed progression-free survival (PFS). Results A total of 140 patients were randomly assigned and treated in arms A (n = 45), B (n = 46), or C (n = 49). PFS was significantly longer in arm B compared with arm A (median, 5.4 months; 95% CI, 3.1 to 6.9 months v 2.8 months; 95% CI, 1.9 to 3.6 months; stratified hazard ratio, 0.389; 95% CI, 0.235 to 0.643; P = .0002). Arm C did not experience improved PFS compared with arm A (1.6 months; 95% CI, 1.4 to 2.9; stratified hazard ratio, 0.863; 95% CI, 0.550 to 1.357; P = .5053). The most common grade 3 or worse adverse events (arms A, B, and C) were neutropenia (36%, 33%, and 39%), fatigue (13%, 30%, and 20%), febrile neutropenia (13%, 17%, and 6.1%), and anemia (6.7%, 13%, and 14%, respectively). Conclusion The addition of ramucirumab to docetaxel met the prespecified efficacy end point for prolonging PFS in patients with locally advanced or metastatic urothelial carcinoma receiving second-line treatment and warrants further investigation in the phase III setting.

scholarly journals Cabozantinib in the treatment of advanced renal cell carcinoma in adults following prior vascular endothelial growth factor targeted therapy: clinical trial evidence and experience

2018 ◽  
Vol 10 (3) ◽  
pp. 109-123 ◽  
Author(s):  
Susanne Osanto ◽  
Tom van der Hulle
Keyword(s):  
Renal Cell Carcinoma ◽  
Vascular Endothelial Growth Factor ◽  
Targeted Therapy ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Line Treatment ◽  
Second Line ◽  
Once Daily ◽  
Endothelial Growth Factor

Cabozantinib is an oral multitargeted tyrosine kinase inhibitor (TKI) that potently inhibits MET and AXL, both associated with poor prognosis in renal cell carcinoma (RCC), next to vascular endothelial growth factor receptor 2, KIT, FLT3 and RET. Chronic treatment with vascular endothelial growth factor receptor (VEGFR)-targeting sunitinib upregulates MET and AXL in RCC, indicating that cabozantinib may be particularly effective in patients with advanced RCC whose disease progressed on prior VEGFR-targeted treatment. Cabozantinib (60 mg once daily) has been investigated in comparison to everolimus (10 mg once daily) in a phase III randomized controlled trial (RCT) in 658 patients with advanced RCC of whom 71% had received one prior and 29% had received at least two prior lines of VEGR-targeted therapy. This study demonstrated highly significant improved progression-free survival of 7.4 months versus 3.9 months with a hazard ratio (HR) of 0.51 [95% confidence interval (CI) 0.41–0.62] in favour of cabozantinib. Cabozantinib also showed a superior overall survival of 21.4 months versus 16.5 months (HR 0.66; 95% CI 0.53–0.83). Objective response rate was higher in cabozantinib-treated patients, 17% versus 3%. Clinical benefit was shown in all subgroups of patients, including in patients with bone or visceral metastases. The safety profile was acceptable with manageable side effects. Based on this study, cabozantinib is a highly effective approved second-line treatment option for patients with advanced RCC with a manageable toxicity profile. Other recently approved second-line agents include checkpoint inhibitor nivolumab and VEGF-targeting agent lenvatinib combined with everolimus. In the absence of predictive markers as well as head-to-head comparisons of these three recently approved treatments, the choice between these drugs in second-line treatment will probably be made based on comorbidities, tolerability of previous treatment and presence of high tumour burden with rapidly progressive disease. Future pretreatment assessment of MET and AXL tumour aberration may aid clinicians to make a rational choice between currently approved second-line treatment options.

scholarly journals Large Skin Ulcer and Delayed Wound Healing around a Colostomy in a Patient with Metastatic Colorectal Cancer Receiving Vascular Endothelial Growth Factor Receptor-2 Inhibitor Therapy

2019 ◽  
Vol 12 (2) ◽  
pp. 370-375 ◽  
Author(s):  
Koichi Taira ◽  
Yuji Nadatani ◽  
Shinji Hirano ◽  
Kiyoshi Maeda ◽  
Yasuhiro Fujiwara
Keyword(s):  
Colorectal Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Line Treatment ◽  
Second Line ◽  
Endothelial Growth Factor ◽  
Large Skin

Ramucirumab is an antiangiogenic agent targeting vascular endothelial growth factor receptor (VEGF)-2 that has been approved for second-line treatment of patients with metastatic colorectal cancer. VEGF-targeted therapy has various distinctive adverse effects owing to its antitumour effects. However, little is known with regard to its skin toxicity, such as its ability to cause skin ulcers. We report a case of large skin ulceration around a colostomy and delayed healing caused by ramucirumab. A 58-year-old patient diagnosed with rectal cancer with liver and lung metastases. He was administered folinic acid, fluorouracil (5-FU), and oxaliplatin (FOLFOX) and bevacizumab as first-line treatment. A laparoscopic colostomy was performed for suspected worsening of the bowel obstruction. He was then administered folinic acid, 5 fluorouracil, and irinotecan (FOLFIRI) and ramucirumab as second-line treatment after surgery. However, dehiscence and a small skin ulceration caused by ramucirumab developed around the colostomy which increased in size and became necrotic; therefore, he was administered only FOLFIRI, without ramucirumab. The ulcer decreased in size slightly with surgical debridement and showering. He resumed FOLFIRI and ramucirumab.

A single-arm, multicenter, open-label phase 2 trial of surufatinib in patients with unresectable or metastatic biliary tract cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16123-e16123
Author(s):  
Yuxian Bai ◽  
Jianming Xu ◽  
Huichuan Sun ◽  
Chunmei Bai ◽  
Ru Jia ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Line Treatment ◽  
Second Line ◽  
Phase 2 ◽  
Open Label ◽  
Tract Cancer ◽  
Open Label Phase ◽  
Endothelial Growth Factor

e16123 Background: Several clinical studies of vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) therapy as second-line treatment for biliary tract cancer (BTC) has demonstrated moderate efficacy. In this study, surufatinib was evaluated as a second-line VEGFR therapy in BTC patients. Methods: This was a single-arm, multi-center, open-label phase 2 study conducted in China. The study enrolled eligible BTC patients who progressed after fist-line chemotherapy. Patients received surufatinib monotherapy as second-line treatment, at doses of 300 mg, once daily, in 28-day cycles. Tumor assessments were performed every 8 weeks ± 7 days according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Results: As of Nov. 30, 2018, a total of 39 BTC patients, including 29 (74.4%) with intrahepatic cholangiocarcinoma, 5 (12.8%) with extrahepatic cholangiocarcinoma, and 5 (12.8%) with gallbladder cancer, were enrolled and treated with surufatinib. Sixteen-week progression-free survival (PFS) rate was 46.33% (95% confidence interval [CI], 24.38‒65.73), with median PFS of 3.7 months and median overall survival (OS) of 6.9 months. In addition, results from subgroup and post-hoc analyses suggested the trends of better clinical efficacy in patients with tumor locations inside the liver, or with lower baseline values of CA19-9 (≤ 1000 IU/mL) and CEA (≤ 3 ng/mL). The top three treatment-related adverse events (TRAEs) with severity of Grade ≥ 3 included blood bilirubin increased (20.5%), hypertension (17.9%), and proteinuria (12.8%). Conclusions: When applied in the treatment of BTC patients, surufatinib monotherapy has offered moderate clinical efficacy and has demonstrated favorable tolerability and safety profiles. Moreover, surufatinib further boosting the antitumor effects of cancer immunotherapy is desirable. Clinical trial information: NCT02966821.

scholarly journals Development of pyogenic granuloma with strong vascular endothelial growth factor receptor-2 expression during ramucirumab treatment

2019 ◽  
Vol 12 (11) ◽  
pp. e231464 ◽  
Author(s):  
Tatsuya Ibe ◽  
Yoichiro Hamamoto ◽  
Mikage Takabatake ◽  
Shingo Kamoshida
Keyword(s):  
Lung Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Angiogenesis Inhibitor ◽  
Growth Factor Receptor ◽  
Pyogenic Granuloma ◽  
Vascular Endothelial ◽  
Line Treatment ◽  
Vascular Tumour ◽  
Endothelial Growth Factor

The angiogenesis inhibitor ramucirumab (IMC-1121B) is a fully humanised IgG1 monoclonal antibody targeting the extracellular domain of vascular endothelial growth factor receptor 2. Ramucirumab has been approved as a second-line treatment for lung cancer. Pyogenic granuloma is an acquired, benign vascular tumour of the skin or mucous membrane. We encountered a patient with pyogenic granuloma who was treated with ramucirumab. The patient was a 48-year-old Japanese woman with advanced lung cancer who had been heavily pretreated using several lines of chemotherapy. Ramucirumab was administered as the fifth-line treatment with docetaxel. After 10 days, a painless rice-coloured or pink papule appeared on her finger. One month later, it increased in size to 20 mm. We examined the pathological condition by immunostaining using the resected specimen diagnosed as pyogenic granuloma. Paradoxically, this vascular tumour arose during the administration of an angiogenesis inhibitor.

Fortgeschrittenes medulläres Schilddrüsenkarzinom: Vandetanib verbessert das progressionsfreie Überleben

2012 ◽  
Vol 03 (02) ◽  
pp. 93-92
Author(s):  
Alexander Kretzschmar
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Medulläres Schilddrüsenkarzinom ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Vandetanib ist ein oraler Hemmer des RET-Kinase-, VEGF (Vascular Endothelial Growth Factor Receptor)- und EGFR (Epidermal Growth Factor Receptor)-Signalwegs. In einer zulassungsrelevanten, randomisierten, doppelblinden, placebokontrollierten Phase- III-Studie verlängerte der Tyrosinkinasehemmer das progressionsfreie Überleben (PFS) signifikant länger als Placebo.

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