(UroToday.com) In this abstract, Ms. Spieler looks at the timing of adjuvant vs. progression-triggered treatment with gemcitabine in platinum-ineligible patients with pT3-4 or N+M0 urothelial carcinoma following radical cystectomy.
As background, cisplatin-based chemotherapy is the preferred perioperative treatment in muscle-invasive Urothelial Carcinoma of the Urinary Bladder (UCUB). Nevertheless, a certain amount of patients remain ineligible for platinum-based chemotherapy. The AUO-AB 22-00 trial aimed to compare adjuvant single-agent gemcitabine versus single-agent gemcitabine at progression (salvage setting) in platinum-ineligible patients with pT3-4 and/or pN+ M0 UCUB.
In this randomized multicenter phase 3 study, 115 patients from 29 hospitals across Germany were randomly assigned to either Adjuvant Chemotherapy (AC) with gemcitabine 1250mg/m2 on day 1 and 8 of a 21-day cycle for a maximum of 6 cycles or to the same procedure at progression. Eligible patients had histologically proven UCUB, pT3-4 and/or pN1-N2 disease after radical cystectomy and lymphadenectomy and no evidence of microscopic residual disease. All patients were not suitable for platinum-based chemotherapy. Neither patients nor investigators were masked.
The study's primary endpoint was Progression-Free Survival (PFS). Secondary endpoints were Overall Survival (OS), toxicity, and quality of life. The analysis was done with the intention to treat. Due to poor recruitment, the trial was prematurely closed with 115 of the planned 178 patients.
Between July 2000 until December 2008, 115 patients were randomly assigned to the trial (59 to AC and 56 to treatment at progression), and followed up until the data cutoff of December 23, 2020.
After a median follow-up of 2 years (IQR 0-11), 42 (71%) of 59 patients in the AC treatment group had progressed or died compared with 42 (75%) of 56 in the group treated at progression.
AC with gemcitabine did not prolong PFS compared with treatment at progression (HR 0,76; 95% CI 0,49-1,18; p=0,218), with 5-year PFS of 36,2% (95% CI 22,8%-49,7%) in the adjuvant gemcitabine group and 22,2% (95% CI 11,5%-35,1%) in the group treated at progression. No significant improvement in OS was noted (HR 0,839; 95% CI 0,57-1,236; p=0,375), with 5-year OS of 44,1% (95% CI 31,2%-56,2%) and 30,4% (95% CI 19%-42,5%), respectively.
These results can be seen before:
Regarding the adverse events (AE), grade 3-4 myelosuppression occurred in 9 (18%) of 51 patients that received treatment in the AC gemcitabine group vs. 6 (40%) of 15 in the group treated at progression. Further grade 3-4 AEs were nausea/emesis (6 (12%) vs. 2 (13%)), elevated liver enzymes (0 vs. 3 (20%)) and stomatitis (1 (2%) vs. 0).
Based on the data above, the authors conclude that there was no difference in terms of PFS and OS for platinum-ineligible patients receiving adjuvant gemcitabine chemotherapy after radical cystectomy compared to patients treated at progression. These findings underline the importance of the development of new perioperative treatment approaches for platinum-ineligible UCUB patients, as single agent gemcitabine is not the right maintenance therapy.
Presented by: N. Spieler, Homburg/Saar, Germany
Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Assistant Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @tchandra_uromd on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.