Original Study
Real-World Vinflunine Outcomes in Bladder Cancer in a Single-Institution Study: Moving Beyond Clinical Trials Guillaume Moriceau,1 Alexis Vallard,2 Romain Rivoirard,1 Benoîte Méry,1 Sophie Espenel,2 Julien Langrand-Escure,2 Majed Ben Mrad,2 Guoping Wang,2 Peng Diao,2 Cécile Pacaut,1 Aline Guillot,1 Olivier Collard,1 Pierre Fournel,1 Nicolas Magné2 Abstract Vinflunine resulted in better survival compared to best supportive care for selected patients with failure of prior therapy with locally advanced or metastatic transitional cell cancer of urothelial tract (TCCU). Our real-life experience of vinflunine for 19 unselected TCCU patients in poorer condition than those in the reference trials shows similar median progression-free survival to the reference study (3.0 months). Purpose: Intravenous vinflunine 320 mg/m2 every 3 weeks plus best supportive care resulted in better overall survival in comparison with best supportive care alone for eligible patients with failure of prior therapy with locally advanced or metastatic transitional cell cancer of urothelial tract (TCCU). The objective of the present study was to describe our real-life experience of vinflunine for treatment of patients with TCCU. Patients and Methods: We retrospectively investigated all patients with TCCU who received at least 1 cycle of vinflunine. Results: Nineteen patients were treated between May 2010 and March 2014 in a compassionate-use program. Performance status was poor in our real-life cohort, with 6 patients (32%) with an Eastern Cooperative Oncology Group performance status of 2. Median duration of vinflunine treatment was 2.4 months (range, 0-4.3 months), and median number of cycles was 3 (range, 1-6). Total response rate was 32%, with partial responses only. Disease control rate was 53%, with a median duration of 7.7 months (range, 6.0-9.4 months). Median progression-free survival was 87 days, or 2.9 months (range, 0.7-11.7 months). After vinflunine treatment, 42% of patients received from 1 to 3 additional lines of chemotherapy. The most frequent grade 4 toxicities were constipation (26%), with 3 intestinal obstructions (16%) and 1 mechanical ileus (5%); and asthenia and fatigue (21%). Conclusion: Vinflunine, as a TCCU second-line chemotherapy, brings benefits, particularly in cases where there is no alternative treatment. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2015 Elsevier Inc. All rights reserved. Keywords: Bladder cancer, Chemotherapy, Efficacy, Tolerance, Transitional cell carcinoma
Introduction Over the past decade, more than 30 new anticancer drugs obtained an agreement and were marketed in France. It cost the French national health insurance program a billion euros in 2010.1 1
Medical Oncology Department Radiation Oncology Department Lucien Neuwirth Cancer Institute, Saint Priest en Jarez, France 2
Submitted: May 3, 2015; Accepted: May 29, 2015 Address for correspondence: Nicolas Magné, MD, PhD, Département de Radiothérapie, Institut de Cancérologie Lucien Neuwirth, 108 bis avenue Albert Raimond, 42270 Saint-Priest-en-Jarez, France Fax: þ33 4 77 91 71 97; e-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2015.05.008
Locally advanced or metastatic transitional cell cancer of urothelial tract (TCCU) is a chemotherapy-sensitive tumor whose first-line standard treatment is a cisplatin-based therapy.2-4 The response rate of second-line chemotherapy has been demonstrated to be much better for patients after their disease fails to respond to neoadjuvant or adjuvant chemotherapy than for patients treated after failure of prior therapy for locally advanced or straightforward metastatic TCCU.5 Unlike renal cancers, phase 2 clinical trials that tested targeted therapies with TCCU did not demonstrate convincing outcomes.6 Until 2009, there was no approved or well-established second-line treatment for TCCU.7 Intravenous vinflunine (Javlor; Pierre Fabre Médicament, Paris, France) provided 320 mg/m2 every 3 weeks plus best supportive
Clinical Genitourinary Cancer Month 2015
-1
Real-World Vinflunine Outcomes in Bladder Cancer care (BSC) has shown a better overall survival (OS) versus BSC alone for eligible patients who have experienced failure of prior therapy for straightforward metastatic TCCU (OS, 6.9 vs. 4.3 months; hazard ratio, 0.78; 95% confidence interval [CI], 0.61-0.99). In the intent-to-treat population, the difference in OS was not statistically significant (6.9 vs. 4.6 months; hazard ratio, 0.88; 95% CI, 0.69-1.12).8 On the basis of these data, in 2010
vinflunine became a European Medicines Agencyeapproved TCCU second-line therapy option in Europe.9,10 However, in early 2012, vinflunine was removed from the list of reimbursed medicines in France. It thus became harder for oncologists to prescribe vinflunine for adult patients with advanced or metastatic platinum-resistant TCCU. However, there are not many other therapies that can be used for this indication.
Table 1 Patient and Treatment Characteristics Bellmunt et al8 Vinflunine D BSC Arm
This Study
253
19
Female
NA
1 (5%)
Male
NA
18 (95%)
Characteristic No. of patients
P
Gender
Age
Real-World Vinflunine Outcomes in Bladder Cancer in a Single-Institution Study: Moving Beyond Clinical Trials Guillaume Moriceau,1 Alexis Vallard,2 Romain Rivoirard,1 Benoîte Méry,1 Sophie Espenel,2 Julien Langrand-Escure,2 Majed Ben Mrad,2 Guoping Wang,2 Peng Diao,2 Cécile Pacaut,1 Aline Guillot,1 Olivier Collard,1 Pierre Fournel,1 Nicolas Magné2 Abstract Vinflunine resulted in better survival compared to best supportive care for selected patients with failure of prior therapy with locally advanced or metastatic transitional cell cancer of urothelial tract (TCCU). Our real-life experience of vinflunine for 19 unselected TCCU patients in poorer condition than those in the reference trials shows similar median progression-free survival to the reference study (3.0 months). Purpose: Intravenous vinflunine 320 mg/m2 every 3 weeks plus best supportive care resulted in better overall survival in comparison with best supportive care alone for eligible patients with failure of prior therapy with locally advanced or metastatic transitional cell cancer of urothelial tract (TCCU). The objective of the present study was to describe our real-life experience of vinflunine for treatment of patients with TCCU. Patients and Methods: We retrospectively investigated all patients with TCCU who received at least 1 cycle of vinflunine. Results: Nineteen patients were treated between May 2010 and March 2014 in a compassionate-use program. Performance status was poor in our real-life cohort, with 6 patients (32%) with an Eastern Cooperative Oncology Group performance status of 2. Median duration of vinflunine treatment was 2.4 months (range, 0-4.3 months), and median number of cycles was 3 (range, 1-6). Total response rate was 32%, with partial responses only. Disease control rate was 53%, with a median duration of 7.7 months (range, 6.0-9.4 months). Median progression-free survival was 87 days, or 2.9 months (range, 0.7-11.7 months). After vinflunine treatment, 42% of patients received from 1 to 3 additional lines of chemotherapy. The most frequent grade 4 toxicities were constipation (26%), with 3 intestinal obstructions (16%) and 1 mechanical ileus (5%); and asthenia and fatigue (21%). Conclusion: Vinflunine, as a TCCU second-line chemotherapy, brings benefits, particularly in cases where there is no alternative treatment. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2015 Elsevier Inc. All rights reserved. Keywords: Bladder cancer, Chemotherapy, Efficacy, Tolerance, Transitional cell carcinoma
Introduction Over the past decade, more than 30 new anticancer drugs obtained an agreement and were marketed in France. It cost the French national health insurance program a billion euros in 2010.1 1
Medical Oncology Department Radiation Oncology Department Lucien Neuwirth Cancer Institute, Saint Priest en Jarez, France 2
Submitted: May 3, 2015; Accepted: May 29, 2015 Address for correspondence: Nicolas Magné, MD, PhD, Département de Radiothérapie, Institut de Cancérologie Lucien Neuwirth, 108 bis avenue Albert Raimond, 42270 Saint-Priest-en-Jarez, France Fax: þ33 4 77 91 71 97; e-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2015.05.008
Locally advanced or metastatic transitional cell cancer of urothelial tract (TCCU) is a chemotherapy-sensitive tumor whose first-line standard treatment is a cisplatin-based therapy.2-4 The response rate of second-line chemotherapy has been demonstrated to be much better for patients after their disease fails to respond to neoadjuvant or adjuvant chemotherapy than for patients treated after failure of prior therapy for locally advanced or straightforward metastatic TCCU.5 Unlike renal cancers, phase 2 clinical trials that tested targeted therapies with TCCU did not demonstrate convincing outcomes.6 Until 2009, there was no approved or well-established second-line treatment for TCCU.7 Intravenous vinflunine (Javlor; Pierre Fabre Médicament, Paris, France) provided 320 mg/m2 every 3 weeks plus best supportive
Clinical Genitourinary Cancer Month 2015
-1
Real-World Vinflunine Outcomes in Bladder Cancer care (BSC) has shown a better overall survival (OS) versus BSC alone for eligible patients who have experienced failure of prior therapy for straightforward metastatic TCCU (OS, 6.9 vs. 4.3 months; hazard ratio, 0.78; 95% confidence interval [CI], 0.61-0.99). In the intent-to-treat population, the difference in OS was not statistically significant (6.9 vs. 4.6 months; hazard ratio, 0.88; 95% CI, 0.69-1.12).8 On the basis of these data, in 2010
vinflunine became a European Medicines Agencyeapproved TCCU second-line therapy option in Europe.9,10 However, in early 2012, vinflunine was removed from the list of reimbursed medicines in France. It thus became harder for oncologists to prescribe vinflunine for adult patients with advanced or metastatic platinum-resistant TCCU. However, there are not many other therapies that can be used for this indication.
Table 1 Patient and Treatment Characteristics Bellmunt et al8 Vinflunine D BSC Arm
This Study
253
19
Female
NA
1 (5%)
Male
NA
18 (95%)
Characteristic No. of patients
P
Gender
Age
