Clinical Outcomes of Platinum-ineligible Patients with Advanced Urothelial Carcinoma Treated With First-line PD1/L1 Inhibitors

Pond, Gregory R.; Agarwal, Archana; Ornstein, Moshe Chaim; García, Jorge A.; Gupta, Ruby; Grivas, Petros; Drakaki, Alexandra; Lee, Jae‐Lyun; Kanesvaran, Ravindran; Lorenzo, Giuseppe Di; Verolino, Pasquale; Barata, Pedro C.; Bilen, Mehmet Asım; Hussain, Syed A.; Curran, Catherine; Sonpavde, Guru

doi:10.1016/j.clgc.2021.04.008

Cited by 21 publications

(9 citation statements)

References 21 publications

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“…In contrast to our findings, the Keynote-052 trial, that aimed to evaluate the safety and antitumor activity of first-line pembrolizumab in subgroups of cisplatin-ineligible older patients (aged ≥ 65 and ≥75 years old) with advanced UC, including those with ECOG PS 2, found that neither age nor poor PS appeared to have an impact on the efficacy of pembrolizumab [ 16 ]. Another study which assessed different PD-1/PD-L1 inhibitors in UC cisplatin-ineligible patients concluded that anemia and liver metastases were associated with a worse survival [ 17 ]. In our population, age and ECOG PS score at C1 were not found to be significant associated with prognosis, but ECOG PS score of 2 at diagnosis has been statistically associated with a poorer OS.…”

Section: Discussionmentioning

confidence: 99%

Clinical Benefit of Pembrolizumab in Advanced Urothelial Cancer Patients in Real-Life Setting: An Efficacy and Safety Monocentric Study

et al. 2022

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Background: Pembrolizumab is approved for patients with metastatic urothelial carcinoma (UC) who progressed under platinum therapy. The aim of this study was to assess the efficacy and safety of pembrolizumab in a cohort of real-life UC patients. Methods: This retrospective, observational study included advanced UC patients treated with pembrolizumab in a single institution in France. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS) at 6 months. Secondary endpoints were objective response rate (ORR), duration of response (DOR), disease control rate (DCR) and safety. Results: 78 patients were included in the study. The median OS was 7.3 months (3.8–12.2). The estimated OS rate at 6 months was 61.5% (50.5–72.6). The median PFS was 3.1 months (1.4–7.2). The estimated PFS rate at 6 months was 42.3% (31.1–53.5). The best ORR was 35.9%. The mean DOR was 95.5 days. The DCR was 30.8%. The most common treatment-related adverse events (AEs) of any grade were fatigue (46.2%), diarrhea (11.5%), pruritus (10.3%) and nausea (9.0%). There were no grade 3 AEs that occurred with an incidence of 5% or more. Conclusion: Our results confirmed those of randomized clinical trials concerning the treatment with pembrolizumab in patients with advanced UC that progressed after platinum-based chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Clinical Benefit of Pembrolizumab in Advanced Urothelial Cancer Patients in Real-Life Setting: An Efficacy and Safety Monocentric Study

et al. 2022

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“…Although prior studies have examined survival outcomes in routine-care UC patients receiving immunotherapy, none have explicitly adjusted for patient characteristic differences between routine-care and trial patients. 4 Without adjusting comparisons of real-world and clinical trial outcomes, the extent to which the efficacy-effectiveness gap is attributable to differences in these characteristics versus other factors is unknown. 5 In this study, we use survival reconstruction and matching-adjusted indirect comparisons (MAIC) weighting to facilitate comparisons of ICI treatment outcomes between the pivotal KEYNOTE-052 trial participants and routine-care populations.…”

Section: Introductionmentioning

confidence: 99%

“…To better inform clinicians and patients of first‐line immunotherapy's real‐world effectiveness for aUC patients, it is critical to examine residual differences in survival outcomes between trial and routine‐care populations aside from those attributable to differences in patient characteristics. Although prior studies have examined survival outcomes in routine‐care UC patients receiving immunotherapy, none have explicitly adjusted for patient characteristic differences between routine‐care and trial patients 4 . Without adjusting comparisons of real‐world and clinical trial outcomes, the extent to which the efficacy‐effectiveness gap is attributable to differences in these characteristics versus other factors is unknown 5 .…”

Section: Introductionmentioning

confidence: 99%

Comparing survival in trial‐ versus routine‐care advanced urothelial cancer patients on immune checkpoint blockade

Wang,

Hubbard,

Mamtani

2024

Pharmacoepidemiology and Drug

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PurposeAlthough recent trials involving first‐line immune checkpoint inhibitors have expanded treatment options for patients with advanced urothelial carcinoma (aUC) who are ineligible for standard cisplatin‐based chemotherapy, there exists limited evidence for whether trial efficacy translates into real‐world effectiveness for patients seen in routine care. This retrospective cohort study compares differences in overall survival (OS) between KEYNOTE‐052 trial participants and routine‐care patients receiving first‐line pembrolizumab monotherapy.MethodsA routine‐care patient cohort was constructed from the Flatiron Health database using trial eligibility criteria and was weighted to balance EHR and trial patient characteristics using matching‐adjusted indirect comparisons.ResultsThe routine‐care cohort was older, more likely to be female, and more often cisplatin‐ineligible due to renal dysfunction. ECOG performance status was comparable between the cohorts. Median OS was 9 months (95% CI 7–16) in the weighted routine‐care cohort and 11.3 months (9.7–13.1) in the trial cohort. No significant differences between the Kaplan–Meier OS curves were detected (p = 0.76). Survival probabilities were similar between the weighted routine‐care and trial cohorts at 12‐, 24‐, and 36‐ months (0.45 vs. 0.47, 0.31 vs. 0.31, 0.26 vs. 0.23, respectively). Notably, routine care patients had modestly lower survival at 3 months compared to trial participants (0.69 vs. 0.83, respectively).ConclusionOur results provide reassurance that cisplatin‐ineligible aUC patients receiving first‐line immunotherapy in routine care experience similar benefits to those observed in trial patients.

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“… 2 Patients ineligible for cisplatin-based chemotherapy are also frequently ineligible for carboplatin-containing regimens; treatment options for these patients include pembrolizumab (anti–programmed cell death-1 [PD-1]) and atezolizumab (anti–programmed cell death ligand-1 [PD-L1]) regardless of tumor PD-L1 status. 3 However, outcomes for platinum-ineligible patients treated with anti–PD-1/PD-L1 agents are poor, with a median OS of 10.4 months, 4 and there remains a high unmet need for new treatments in this population.…”

Section: Introductionmentioning

confidence: 99%

Durvalumab Plus Olaparib in Previously Untreated, Platinum-Ineligible Patients With Metastatic Urothelial Carcinoma: A Multicenter, Randomized, Phase II Trial (BAYOU)

Rosenberg

Park

Kozlov

et al. 2023

JCO

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PURPOSE Homologous recombination repair gene mutations (HRRm) are common in urothelial carcinoma (UC), rendering tumor cells sensitive to poly (ADP-ribose) polymerase (PARP) inhibition. We assessed efficacy and safety of durvalumab (anti–programmed cell death ligand-1) plus olaparib (PARP inhibitor) in patients with metastatic UC (mUC). METHODS This randomized, multicenter, double-blind, phase II trial enrolled untreated, platinum-ineligible patients with mUC. Patients (N = 154) were randomly assigned 1:1 to receive durvalumab (1,500 mg intravenously once every 4 weeks) plus olaparib (300 mg orally, twice daily) or durvalumab plus placebo. The primary end point was progression-free survival (PFS) assessed by investigators per RECIST version 1.1. Secondary end points included overall survival in all patients and PFS in patients with HRRm. RESULTS Overall, median PFS was 4.2 months (95% CI, 3.6 to 5.6) for durvalumab plus olaparib and 3.5 months (95% CI, 1.9 to 5.1) for durvalumab plus placebo (hazard ratio [HR], 0.94; 95% CI, 0.64 to 1.39; log-rank P value, .789). Median overall survival was 10.2 months (95% CI, 7.0 to 13.9) and 10.7 months (95% CI, 7.2 to 17.3), respectively (HR, 1.07; 95% CI, 0.72 to 1.61). In the 20% of patients with HRRm, median PFS was 5.6 months (95% CI, 1.9 to 8.1) and 1.8 months (95% CI, 1.7 to 2.2), respectively (HR, 0.18; 95% CI, 0.06 to 0.47). Treatment-related grade 3 or 4 adverse events occurred in 18% and 9% of patients, respectively. CONCLUSION Adding olaparib to durvalumab did not improve survival outcomes in an unselected mUC population. Efficacy outcomes with durvalumab were similar to those reported for other anti–programmed cell death-1/programmed cell death ligand-1 agents. However, the results of secondary analyses suggest a potential role for PARP inhibition in patients with UC harboring HRRm.

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Clinical Outcomes of Platinum-ineligible Patients with Advanced Urothelial Carcinoma Treated With First-line PD1/L1 Inhibitors

Cited by 21 publications

References 21 publications

Clinical Benefit of Pembrolizumab in Advanced Urothelial Cancer Patients in Real-Life Setting: An Efficacy and Safety Monocentric Study

Clinical Benefit of Pembrolizumab in Advanced Urothelial Cancer Patients in Real-Life Setting: An Efficacy and Safety Monocentric Study

Comparing survival in trial‐ versus routine‐care advanced urothelial cancer patients on immune checkpoint blockade

Durvalumab Plus Olaparib in Previously Untreated, Platinum-Ineligible Patients With Metastatic Urothelial Carcinoma: A Multicenter, Randomized, Phase II Trial (BAYOU)

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