Long-term efficacy and safety outcomes of the modified (simplified) combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) as front-line therapy for unresectable or metastatic urothelial cancer (UC)

284 Background: MVAC and cisplatin-gemcitabine (CG) are the established standard of care for untreated patients (pts) with locally advanced-metastatic UC. CG is the preferred choice in most cases due to the better toxicity profile. Modifying MVAC by reducing side-effects may have the potential to improve efficacy. Methods: Data relative to unresectable T/N+/M+ pts entering sequential single-institution trials were collected. Chronologically, these changes to classic MVAC were provided: deletion of day 22 and administration of 25 mg/m2CDDP d2-5 (modified MVAC [mMVAC]); deletion of day 22 only, and deletion of days 15 and 22 in a 3-week schedule (simplified [s]MVAC1 and 2). 4-6 cycles were provided. Multivariable analysis was undertaken for recognized clinical variables. ITT analysis was applied. Results: From 09/86 to 04/12, 157 pts were treated (25 mMVAC, 72 sMVAC1, 60 sMVAC2). 84% had a bladder primary, 70% had distant metastases, 53% and 36% had nodal and visceral mets, respectively. 43.9% had a Bajorin score 1-2. 65.8% attained a complete (19.1%) or partial response (46.7%), 24.3% a stable disease, with no difference among regimens. After a median follow up of 87 mos (IQR 37-161), median (95% CI) PFS was 10.2 mos (8.4-10.8) and median OS was 19.5 mos (16.3-24.1). 2yr (95% CI) PFS and 5yr OS were 30.9% (23.8-40.1) and 25.3% (18.8-34.1). Responses were mainly seen in nodal mets (OR: 2.48, 95%CI, 1.12-5.54). Presence of visceral (HR: 2.42, 95%CI, 1.37-4.30), nodal mets (HR: 1.70, 95%CI, 1.07-2.69) and mMVAC regimen (HR: 1.73, 95%CI, 1.02-2.92) were negative prognostic factors for OS. G3-4 toxicities were similar among regimens and were 36% neutropenia, 14% thrombocytopenia, 12% anemia, 10% mucositis, and 4% renal toxicity. 2 pts died for toxicity. Conclusions: Simplifying MVAC schedule may result in improved activity and efficacy while reducing toxicity. Though retrospective, the combined results of MVAC modification would claim a benefit over either classic/dose-dense MVAC or CG in terms of efficacy and safety. A reappraisal of the upfront management of advanced/metastatic UC is warranted.