scholarly journals Long Term Progression Free Survival Achieved by Maintenance “Second–Line” Polychemotherapy with Gemcitabine/Paclitaxel in Metastatic Urothelial Cancer of the Renal Pelvis—A Case Report

2010 ◽  
Vol 01 (04) ◽  
pp. 229-231
Author(s):  
Andreas Bannowsky ◽  
Hermann Ahlen ◽  
Klaus-Peter Jünemann
Keyword(s):  
Case Report ◽  
Renal Pelvis ◽  
Urothelial Cancer ◽  
Progression Free Survival ◽  
Second Line ◽  
Free Survival ◽  
Metastatic Urothelial Cancer

scholarly journals Phase II Trial of Cetuximab With or Without Paclitaxel in Patients With Advanced Urothelial Tract Carcinoma

2012 ◽  
Vol 30 (28) ◽  
pp. 3545-3551 ◽  
Author(s):  
Yu-Ning Wong ◽  
Samuel Litwin ◽  
David Vaughn ◽  
Seth Cohen ◽  
Elizabeth R. Plimack ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Metastatic Setting ◽  
Previously Treated ◽  
Grade 3

Purpose The benefit of salvage chemotherapy is modest in metastatic urothelial cancer. We conducted a randomized, noncomparative phase II study to measure the efficacy of cetuximab with or without paclitaxel in patients with previously treated urothelial cancer. Patients and Methods Patients with metastatic urothelial cancer who received one line of chemotherapy in the perioperative or metastatic setting were randomly assigned to 4-week cycles of cetuximab 250 mg/m2 with or without paclitaxel 80 mg/m2 per week. We used early progression as an indicator of futility. Either arm would close if seven of the initial 15 patients in that arm progressed at the first disease evaluation at 8 weeks. Results We enrolled 39 evaluable patients. The single-agent cetuximab arm closed after nine of the first 11 patients progressed by 8 weeks. The combination arm completed the full accrual of 28 patients, of whom 22 patients (78.5%) had visceral disease. Twelve of 28 patients had progression-free survival greater than 16 weeks. The overall response rate was 25% (95% CI, 11% to 45%; three complete responses and four partial responses). The median progression-free survival was 16.4 weeks (95% CI, 12 to 25.1 weeks), and the median overall survival was 42 weeks (95% CI, 30.4 to 78 weeks). Treatment-related grade 3 and 4 adverse events that occurred in at least two patients were rash (six cases), fatigue (five cases), and low magnesium (three cases). Conclusion Although it had limited activity as a single agent, cetuximab appears to augment the antitumor activity of paclitaxel in previously treated urothelial cancers. The cetuximab and paclitaxel combination merits additional study to establish its role in the treatment of urothelial cancers.

Combination checkpoint immunotherapy and cytotoxic chemotherapy: Pembrolizumab (Pembro) plus either docetaxel or gemcitabine in patients with advanced or metastatic urothelial cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 398-398 ◽  
Author(s):  
Primo Lara ◽  
Laurel Beckett ◽  
Yueju Li ◽  
Mamta Parikh ◽  
Daniel Robles ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Progression Free Survival ◽  
Organ Function ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Initial Cohort ◽  
Secondary Endpoints ◽  
Anti Tumor Activity ◽  
Dose Limiting Toxicity ◽  
Clinical Trial Information

398 Background: Metastatic urothelial cancer (mUC) is only modestly responsive to checkpoint inhibitor immunotherapy; e.g., the PDL1 inhibitor atezolizumab confers only a 16% tumor response rate (RR) in platinum-treated mUC. Chemotherapy is hypothesized to enhance tumoral neoantigen expression thus priming response to PD1-directed immunotherapy. Here we report results from the initial cohort of an investigator-initiated trial of Pembro plus either docetaxel or gemcitabine in platinum-treated mUC patients (pts). Methods: Primary endpoint was safety; secondary endpoints were overall RR and progression-free survival (PFS). Eligible pts had Zubrod PS 0-1, adequate end-organ function, and up to 2 prior lines of chemo (at least 1 platinum-based). Dose limiting toxicity (DLT) was any grade (Gr) 3+ non-heme toxicity, Gr3+ neutropenia w/ fever or infection, or Gr4 platelets (plts), or Gr3 plts with bleeding. In dose level (DL) 1, treatment consisted of Pembro 200 mg IV on D1 q3 weeks plus either docetaxel 75 mg/m2 on D1 (Arm 1) or gemcitabine 1000 mg/m2 on D1&D8 (Arm 2). Results: Overall 12 pts were enrolled in DL1, six in each arm. Median age was 69 years (range 45-84), 8 (67%) male, & 10 (83%) of white race. One pt in each arm had DLT: Gr3 hypophosphatemia in Arm 1, Gr3 diarrhea in Arm 2. Attributable Gr3+ toxicities were seen in 7 (54%). Most common Gr3+ AEs were anemia (5, 38%), fatigue (4, 31%), & neutropenia (4, 31%). There were no treatment related deaths; 3 died from tumor progression (PD). As of 10/2016, 4 pts remain on active therapy. In total 4 pts had confirmed response (1 CR, 3 PR), 2 had stable disease (SD), and 6 had PD for an overall RR of 33% and Disease Control Rate (DCR) of 50%. Arm 1 had an overall RR of 50% (1CR, 2PR, 1SD) and DCR of 67%. Arm 2 had an overall RR of 17% (1PR, 1SD) and DCR of 33%. Median PFS (overall, Arm 1 & 2) were 4.8, 5.7, and 3.7 months. Conclusions: Pembro 200 mg IV q3 weeks plus either full-dose docetaxel or gemcitabine is feasible in platinum-treated mUC pts. Encouraging anti-tumor activity for chemo-immunotherapy was seen in this ongoing study, particularly with Pembro+docetaxel. Further investigation of this approach is warranted. Clinical trial information: NCT02437370.

scholarly journals Pembrolizumab versus chemotherapy in recurrent, advanced urothelial cancer in Japanese patients: a subgroup analysis of the phase 3 KEYNOTE-045 trial

2019 ◽  
Vol 25 (1) ◽  
pp. 165-174 ◽  
Author(s):  
Hiroyuki Nishiyama ◽  
Yoshiaki Yamamoto ◽  
Naoto Sassa ◽  
Kazuo Nishimura ◽  
Kiyohide Fujimoto ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Open Label ◽  
End Points ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Grade 3

Abstract Background The open-label, randomized, active-controlled KEYNOTE-045 study (NCT02256436) showed that second-line pembrolizumab significantly improved overall survival (OS) of patients with advanced/metastatic urothelial cancer (UC) that progressed after first-line platinum-containing chemotherapy, compared with standard chemotherapy (paclitaxel, docetaxel, or vinflunine). Pembrolizumab is approved for patients with bladder cancer in Japan. Patients and methods Analysis was performed in the subgroup of Japanese patients enrolled in the KEYNOTE-045 study. Coprimary end points were OS and progression-free survival (PFS). Objective response rate (ORR) and safety were secondary end points. Results Fifty-two Japanese patients (pembrolizumab, n = 30; chemotherapy, n = 22) were followed up for a median of 26.1 months. Patients who received pembrolizumab compared with chemotherapy had a 19% lower risk for death (hazard ratio [HR] 0.81, 95% CI 0.44–1.50); after adjusting for baseline covariates, the HR for OS was 0.61 (95% CI 0.32–1.15). The 24-month OS rate was higher with pembrolizumab (26.9% vs 14.3%). PFS was 2.0 and 4.9 months for pembrolizumab and chemotherapy, respectively (HR 1.71, 95% CI 0.95–3.08). ORR was similar for pembrolizumab and chemotherapy (20.0% vs 18.2%); durability of response was higher with pembrolizumab: 67% and 33% of patients, respectively, maintained a response for > 12 months. Treatment-related adverse events, including grade 3–5 events, occurred less frequently with pembrolizumab. Conclusions Pembrolizumab provided durable antitumor activity in patients with locally advanced/metastatic UC that progressed after platinum-containing chemotherapy in the overall population and in the Japanese subgroup; safety profile was consistent with that previously observed for pembrolizumab.

Metastatic brain lesions in patients with cervical cancer: a case report

GYNECOLOGY ◽  
2019 ◽  
Vol 21 (3) ◽  
pp. 46-48
Author(s):  
Nadezhda V Sevyan ◽  
Vladislav B Karakhan ◽  
Ali Kh Bekyashev ◽  
David R Naskhletashvili ◽  
Nikolai A Kozlov ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Adverse Event ◽  
Case Report ◽  
Poor Prognosis ◽  
Progression Free Survival ◽  
Brain Lesions ◽  
Free Survival ◽  
Uterine Cervical Carcinoma ◽  
Intracranial Metastases

Brain metastases from uterine cervical carcinoma are very rare. The development of intracranial metastases is a long-term adverse event indicating poor prognosis. In this paper, we present a case of cervical cancer with a brain metastasis in a patient who received combination therapy and demonstrated long-term progression-free survival.

Progression-free survival as an endpoint for clinical trials in first-line metastatic urothelial cancer.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 251-251
Author(s):  
Matt D. Galsky ◽  
Susanne Krege ◽  
Chia-Chin Lin ◽  
Noah M. Hahn ◽  
Thorsten Ecke ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Performance Status ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Phase Ii Trials ◽  
First Line ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
First Line Treatment

251 Background: Advances in the first-line treatment of metastatic urothelial cancer (UC) have proven elusive. The lack of appropriate intermediate endpoints to screen the activity of novel regimens may be a barrier to progress, particularly in this disease state characterized by relatively high response rates but short response durations. Progression-free-survival (PFS) at fixed time points may overcome several of the limitations of response rate-based endpoints, but would be further supported by establishing benchmarks and demonstrating a correlation between PFS and overall survival (OS). Methods: Data were pooled from eight phase II and III trials evaluating first-line cisplatin-based chemotherapy in metastatic UC. Landmark analyses for progression at 3, 6, and 9 months after treatment initiation were performed to minimize lead-time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS. Results: 545 patients were included in the analysis. The median PFS was 7.75 months (95% CI, 7.06, 8.18) and the median OS was 12.35 months (95% CI, 10.97, 13.44). The results of the landmark analysis, adjusted for performance status ≥ 1 and presence of visceral metastases, is shown in the Table. By using the Fleischer model, the estimated correlation between PFS and OS was 0.86 (bootstrap standard error 0.001, 95% CI 0.83, 0.89). Conclusions: PFS at 3, 6, and 9 months predicted OS in this analysis of patients with metastatic UC treated with first-line cisplatin-based chemotherapy. This analysis provides benchmarks, and support, for the use of PFS as an endpoint for phase II trials screening the activity of novel regimens as first-line treatment for metastatic UC. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document