The efficacy and safety of first-line treatment in cisplatin-ineligible advanced upper tract urothelial carcinoma patients: a comparison of PD-1 inhibitor and carboplatin plus gemcitabine chemotherapy

Abstract

Although several programmed cell death (PD)-1 inhibitors are approved for the first-line treatment of advanced urothelial carcinoma, their efficacy remains unknown in cisplatin-ineligible patients with upper tract urothelial carcinoma (UTUC) compared with gemcitabine plus carboplatin. Data for patients with UTUC were retrospectively retrieved from the electronic medical records of nine institutions between 2018 and 2021. Patients considered ineligible for cisplatin who received either PD-1 inhibitors (n = 70) or gemcitabine plus carboplatin (n = 53) were included. Efficacy was assessed using Response Evaluation Criteria in Solid Tumors. Median progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. The objective response rate (ORR) was comparable between the PD-1 inhibitor and carboplatin–gemcitabine groups (38.6% versus 41.5%). Median PFS was 5.0 months (95% confidence interval [CI]: 2.0–8.0) in the PD-1 inhibitor group, versus 7.0 months (95% CI: 5.8–8.2) in the carboplatin–gemcitabine group (hazard ratio [HR] = 0.741, 95% CI: 0.485–1.132, p = .166). Median OS was 18 months (95% CI: 4.1–31.9) in the PD-1 inhibitor group, compared with 14 months (95% CI: 12.1–15.9) in the carboplatin–gemcitabine group (HR = 0.731, 95% CI: 0.426–1.256, p = .257). The duration of response was significantly longer in the PD-1 inhibitor group than in the carboplatin–gemcitabine group (not reached vs. 9 months, p < .001). Treatment-related adverse events were less frequent in the PD-1 inhibitor group than in the carboplatin–gemcitabine group (57.1% vs. 77.3%). In conclusion, PD-1 inhibitors displayed promising efficacy with less toxicity and longer DOR in the first-line treatment of UTUC in patients ineligible for cisplatin-based chemotherapy.

Effectiveness and safety of immune checkpoint inhibitor monotherapy in advanced upper tract urothelial carcinoma: A multicenter, retrospective, real‐world study

“…We previously compared the efficacy and safety of PD-1 inhibitors and carboplatin combined with gemcitabine in the first-line treatment of cisplatin-unfit UTUC patients. 33 Our results support the role of PD-1 inhibitors with comparable survival outcomes, longer DOR, and lower toxicity than carboplatin-gemcitabine for cisplatin-ineligible patients, although PD-1 inhibitors may not surpass cisplatin dominance in the treatment of those eligible patients. In this study, we further explore the effect of ICIs in a second-line setting and provide a full spectrum of efficacy and safety of ICI monotherapy for unresectable or metastatic UTUC as a first-line therapy in cisplatin-ineligible patients or second-line therapy in platinum-refractory patients.…”

“…We previously compared the efficacy and safety of PD‐1 inhibitors and carboplatin combined with gemcitabine in the first‐line treatment of cisplatin‐unfit UTUC patients 33 . Our results support the role of PD‐1 inhibitors with comparable survival outcomes, longer DOR, and lower toxicity than carboplatin‐gemcitabine for cisplatin‐ineligible patients, although PD‐1 inhibitors may not surpass cisplatin dominance in the treatment of those eligible patients.…”

Clinical outcomes of immune checkpoint inhibitor plus nab-paclitaxel in metastatic upper tract urothelial carcinoma

“…However, clinical differences may lead to different treatment responses in UTUC and bladder cancer, as UTUC only constituted a minor proportion of these studies. Previously, we reported comparable oncological outcomes between PD-1 inhibitor monotherapy and carboplatin plus gemcitabine in first-line treatment of cisplatin-ineligible UTUC patients ( 22 ). Meanwhile, PD-1 inhibitor monotherapy is associated with lower toxicity ( 22 ).…”

“…Previously, we reported comparable oncological outcomes between PD-1 inhibitor monotherapy and carboplatin plus gemcitabine in first-line treatment of cisplatin-ineligible UTUC patients ( 22 ). Meanwhile, PD-1 inhibitor monotherapy is associated with lower toxicity ( 22 ). The efficacy of PD-1 inhibitor monotherapy might correlate with various biomarkers, including PD-L1 expression ( 23 ).…”

The combination of oxaliplatin and anti-PD-1 inhibitor promotes immune cells infiltration and enhances anti-tumor effect of PD-1 blockade in bladder cancer

“…Previous research reported that platinum-based chemotherapy, a conventional treatment, may affect the patient’s immune system ( 21 ). Some clinical trials also found that the combination of PD-1 ( 22 )/PD-L1 ( 23 ) inhibitor with platinum-based chemotherapy would enhance the efficacy and safety of monotherapy. Although the immunogenicity caused by platinum drugs is responsible for the effectiveness of combination therapy, the effect of platinum drugs on the TIME is still unknown, especially in BLCA.…”