Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial

Abstract Background To evaluate patient-reported outcomes with ramucirumab plus docetaxel, a regimen which improved progression-free survival in platinum-refractory advanced urothelial carcinoma (aUC). Methods RANGE—a randomized, double-blinded, phase 3 trial in patients with platinum-refractory aUC. Ramucirumab (10 mg/kg) plus docetaxel (75 mg/m2) or placebo plus docetaxel were administered every 21 days until disease progression or unacceptable toxicity. Patients received maximum 10 cycles of docetaxel. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and EuroQoL five-dimensions (EQ-5D-5L) were administered at baseline, start of each cycle, and 30-day follow-up visit. A ≥ 10-point change in QLQ-C30 scores was considered meaningful. Rates of improved/stable scores were compared between treatment arms using Fisher’s exact test. Time to deterioration (TtD) was estimated and compared using Kaplan–Meier estimation and log-rank test. Results Of the 530 patients, ~ 97% patients in each arm provided baseline QLQ-C30 data. On-treatment compliance was ≥ 88% for first 8 cycles. Mean baseline QLQ-C30 scores were similar between arms, with global quality of life (QoL), fatigue, pain, and insomnia having greatest impairment. Postbaseline rates of improved/stable QLQ-C30 scores were similar between treatment arms except for greater improvement in pain score with ramucirumab. TtD of QLQ-C30 scales favored ramucirumab arm. Baseline EQ-5D-5L index and visual analogue scale scores were similar between arms, followed by relatively stable on-treatment scores. EQ-5D-5L scores worsened at post-discontinuation follow-up visit. Conclusions Ramucirumab plus docetaxel did not negatively impact QoL compared with docetaxel alone in platinum-refractory aUC. Improved TtD and tumor associated rates of pain favored ramucirumab treatment. Clinical trail registration NCT02426125. https://clinicaltrials.gov/ct2/show/NCT02426125. Date of registration: April 24th 2015

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Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma (KEYNOTE-361): a randomised, open-label, phase 3 trial

The Lancet Oncology ◽

10.1016/s1470-2045(21)00152-2 ◽

2021 ◽

Author(s):

Thomas Powles ◽

Tibor Csőszi ◽

Mustafa Özgüroğlu ◽

Nobuaki Matsubara ◽

Lajos Géczi ◽

...

Keyword(s):

Urothelial Carcinoma ◽

First Line ◽

Open Label ◽

Phase 3 ◽

First Line Therapy ◽

Line Therapy ◽

Open Label Phase ◽

Advanced Urothelial Carcinoma

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Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study

Current Drug Safety ◽

10.2174/1574886313666181001120752 ◽

2019 ◽

Vol 14 (1) ◽

pp. 31-36

Author(s):

Raafat Abdel-Malek ◽

Kyrillus S. Shohdy ◽

Noha Abbas ◽

Mohamed Ismail ◽

Emad Hamada ◽

...

Keyword(s):

Pilot Study ◽

Adverse Events ◽

Urothelial Carcinoma ◽

Transitional Cell ◽

Chemotherapeutic Agents ◽

Serious Adverse Events ◽

Platinum Based Chemotherapy ◽

Number Of Patients ◽

Advanced Urothelial Carcinoma ◽

Grade 3

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

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