Yet, the evidence for NAC prior to surgical management for UTUC is lacking. The POUT study, a phase III study of adjuvant chemotherapy, reported DFS benefit in this population. However, due to renal impairment from nephrectomy, the neoadjuvant would likely be the ideal setting for chemotherapy administration. In this study, the authors provide results from ECOG-ACRIN 8141, a phase II clinical trial of NAC prior to extirpative surgery for high grade (HG) UTUC. The extirpative surgery planned in all patients was a radical nephroureterectomy (NU) and lymphadenectomy (extent not specified). Again, as understaging is common in UTUC, there was no limitation based on T-stage.
Inclusion criteria: Patients (pts) with HG UTUC (based on biopsy, imaging or visualized mass, and cytology) planned for NU were eligible.
- 4 NAC cycles were assigned by baseline creatinine clearance (CrCl) – this was not randomized!
- CrCl >50: aMVAC (methotrexate 30 mg/m2, vinblastine 3 mg/m2, doxorubicin 30 mg/m2, cisplatin 70 mg/m2 with pegfilgrastim q14 days).
- CrCl ≥30 and ≤ 50: GC (carboplatin AUC 5 D1 and gemcitabine 1000 mg/m2 days 1, 8)
Primary endpoint: pathologic complete response (pCR) rate (ypT0N0), Statistical planning: On each arm, a pCR rate of 18% was of interest vs. a null of 4%. Success was defined as at least 3 pCRs among 28 pts (10.7%)
Accrual goal was 30 pts per arm.
In terms of results, at the time of presentation, from April 2015 to May 2017, 30 patients were enrolled to the aMVAC cohort (CrCl >50). Only 6 patients were enrolled to the GC cohort - which closed for poor accrual in January 2018. Hence, the focus was on the 30 patients accrued to the aMVAC arm.
Of the eligible pts, demographics were as follows: 24 male and 6 female, median age 65 (range 40-84), and median performance status 0. Patients were predominantly white.
Of these 30 patients, 3 patients achieved ypT0N0 at NU (10%, 90% CI [2.9 – 24.6]). Including the patient with clinical CR on preoperative imaging without lymph node dissection at the time of NU (ypT0Nx), the pCR rate was 4/29 (14%, 90% CI [4.9 – 28.8]). Including partial responders, the ≤ypT1 rate exceeded 60%. The median number of chemotherapy cycles was 4 (1-4), 79% of patients completed treatment.
Full response profiles listed below:
In terms of tolerability, only 1 patient on aMVAC arm developed Grade 4 sepsis during cycle 1 and deferred further NAC and NU. Grade 3-4 toxicity rate was 23% on aMVAC arm, no G5 events. 80% of the patients completed treatment per protocol. There was no documentation of progression on chemotherapy.
There was no discussion on the impact on surgery, thought this would be important to know.
Presented by: Jean Hoffman-Censits, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD,
Co-Author: Maneka Puligandla, Boston, MA, Edouard Trabulsi, Elizabeth Plimack, Philadelphia, PA, Elizabeth Kessler, Aurora, CO, Surena F. Matin, Guilherme Godoy, Houston, TX, Ajjai Alva, Ann Arbor, MI, Noah M. Hahn, Michael Carducci, Baltimore, MD, Vitaly Margulis, Dallas , TX
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, @tchandra_uromd at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA