Gemcitabine/paclitaxel/adriamycin (GTA) as a nephron-sparing regimen in urothelial carcinoma: The MD Anderson Cancer Center (MDACC) experience.
Year: 2024
Type: conference-abstract
Abstract: e16576 Background: GTA (Gemcitabine 900 mg/m2 IV; Paclitaxel 135 mg/m2 IV and Adriamycin 30 mg/m2 IV, with pegfilgrastim 6mg SQ on a 14-day cycle) was initially reported from a prospective phase II study of 39 patients (pts) by Siefker-Radtke et al. Urology (2016). We report real-world efficacy and survival outcomes with this nephron-sparing regimen in locally advanced or metastatic urothelial carcinoma (LA/mUC). Methods: We retrospectively reviewed records of n=76 pts with frontline (1L) GTA for LA/mUC between March 2016 and April 2023 at MDACC. Imaging-based best overall responses (BOR) using RECIST v1.1 were noted as partial (PR), stable (SD), progressive (PD) or non-evaluable (NE). We use Kaplan-Meier (KM) method to estimate overall survival (OS) and progression-free survival (PFS) from GTA start, and reverse KM for follow-up (FU). Results: Baseline characteristics (n=76) are shown in Table. Median age at diagnosis was 70.6 [IQR: 65.3 – 76.3]. The decision to start GTA was justified by tumor-related (55, 72.4%) or non-tumor-related (14, 18.4%) renal insufficiency, and general comorbidities (7, 9.2%).n=48 (63.2%) had percutaneous nephrostomy or ureteral stenting before GTA initiation. Pts had a median number of 3 cycles (IQR: 2-5). At GTA start, most pts (38, 50%) had one Barjorin risk factor (either bone/liver/lung mets or ECOG PS ≥2), 28 (36.8%) had none and 10 (13.2%) had both factors. Median OS was 11.3 mo (95% CI: 9.1 – 15.1 mo) with a median FU of 64.8 mo (95% CI: 26.2 – 83.6). Median PFS was 3.4 mo (95% CI: 3.03 – 4.5 mo). Overall response ratewas 26.3%, and BOR to 1L GTA included: PR 20/76 (26.3%), SD 25/76 (32.9%), PD 17/76 (22.4%) and NE 14/76 (18.4%). NE responses were due to transition to cisplatin-based regimens or other therapies in 8/14, toxicity in 3/14, pt death in 2/14 and pt preference in 1/14. GTA dose reduction was required in 15 (19.7%), and serious adverse events leading to hospitalization occurred in 18 (23.7%). Finally, among 69 pts with tumor or non-tumor related renal insufficiency, 16/69 (23.2%) were able to receive cisplatin post-GTA. In a paired t-test analysis of 76 GFR pairs, an improvement in GFR post-GTA was observed compared to pre-GTA GFR, with a significant difference of 11.2 mL/min [95% CI: 7.4 – 14.9, p < 0.0001]. Conclusions: GTA shows modest efficacy as a 1L regimen in LA/mUC. The facilitation of cisplatin-based regimens after GTA in a subset of pts might be explained by restoring patency in partially obstructed collecting systems. This ‘GTA bridging’ strategy may be beneficial for pts for whom nephrostomy or ureteral stenting proves impractical or insufficient to address renal insufficiency. [Table: see text]
Source: Journal of Clinical Oncology
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4399394249