Atezolizumab in Metastatic Urothelial Carcinoma Outside Clinical Trials: Focus on Efficacy, Safety, and Response to Subsequent Therapies

Barata, Pedro C.; Gopalakrishnan, D.; Koshkin, Vadim S.; Mendiratta, Prateek; Karafa, Matt; Allman, Kimberly D; Martin, Allison; Beach, Jordan R.; Profusek, Pam; Tyler, Allison; Wood, Laura S.; Ornstein, Moshe Chaim; Gilligan, Timothy D.; Rini, Brian I.; García, Jorge A.; Grivas, Petros

doi:10.1007/s11523-018-0561-6

Cited by 14 publications

(7 citation statements)

References 35 publications

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“…Thus, patients with PS 2 in the KEYNOTE‐045 trial differ significantly from the actual population of patients with UC and PS 2. Four retrospective studies have assessed efficacy of ICIs in patients with UC and PS ≥2, including any ICI 8 in one study and atezolizumab in three studies 9‐11 . Khaki et al reported a median OS of 8.2 months and ORR of 23% among patients with PS ≥2 and who received an ICI in the second‐line setting or later, which were comparable to the outcomes for patients with PS ≤1 8 .…”

Section: Discussionmentioning

confidence: 95%

“…Conversely, a study of atezolizumab therapy in patients with advanced UC or non‐UC (SAUL study) reported a median OS of 2.3 months and ORR of 5% in patients with PS 2 9 . The other two studies did not focus on patients with PS ≥2, and the reported ORR for the entire cohorts ranged from 17 to 21% 10,11 . These widely divergent outcomes might be attributable to differences in patients’ backgrounds such as the number of risk factors.…”

Section: Discussionmentioning

confidence: 99%

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Pembrolizumab for treating advanced urothelial carcinoma in patients with impaired performance status: Analysis of a Japanese nationwide cohort

et al. 2021

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BackgroundThe benefits of pembrolizumab in patients with advanced urothelial carcinoma (UC) and impaired performance status (PS) remain unknown. This study assessed the safety and efficacy of pembrolizumab in patients with platinum‐refractory UC and Eastern Cooperative Oncology Group PS ≥2 to identify which subgroups may benefit from this drug.MethodsThis retrospective nationwide cohort study collected clinicopathological information for 755 patients from 59 institutions. The overall response rate (ORR) and overall survival (OS) were compared among the patients with PS 0–1, 2, and 3–4. Multivariate analysis was conducted to identify factors predicting OS in patients with PS ≥2.ResultsThe numbers of patients with PS 0–1, 2, and 3–4 were 602, 98, and 55, respectively; the ORRs in these groups were 29.5, 15.3, and 9.1%, respectively, and the median OS times were 14.3, 3.1, and 2.4 months, respectively. In multivariate Cox regression analysis, a neutrophil–lymphocyte ratio (NLR) ≥3.5 (hazard ratio [HR] = 1.897) and liver metastasis (HR = 2.072) were associated with OS in the PS ≥2 subgroup. The median OS of patients with PS ≥2 without either risk factor was 6.8 months, compared with 3.1 months for patients with one risk factor and 2.3 months for patients with both risk factors.ConclusionsPS ≥2 portended worse ORR and OS than PS ≤1 despite a comparable safety profile. Among the patients with impaired PS, patients with NLR <3.5 and no liver metastasis may most greatly benefit from pembrolizumab therapy.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Pembrolizumab for treating advanced urothelial carcinoma in patients with impaired performance status: Analysis of a Japanese nationwide cohort

et al. 2021

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“…Similar multicenter experiences previously reported in the literature suggested that patients progressing to frontline ICI are not likely to receive or benefit from subsequent chemotherapy. 14,18 With the MeeT-URO 1 population, we obtained different results, showing a quite favorable outcome of patients treated with chemotherapy after progressing to ICI. Indeed, the outcome in terms of median PFS (3.5 months) and median OS (9 months) in the overall population was not inferior to that expected from salvage chemotherapy after the first-line polychemotherapy Abbreviations: N, total number of patients; NE, not evaluable; PD, progression of disease; PR, partial response; SD, stable disease.…”

Section: Discussionmentioning

confidence: 97%

Clinical Outcomes of Patients With Metastatic Urothelial Carcinoma After Progression to Immune Checkpoint Inhibitors: A Retrospective Analysis by the Meet-Uro Group (Meet-URO 1 Study)

Bersanelli

Buti

Cortellini

et al. 2021

Clin Med Insights Oncol

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Background: Immune checkpoint inhibitors (ICIs) are currently the standard of care for metastatic urothelial cancer (mUC) after the failure of previous platinum-based chemotherapy. The choice of further therapy after ICI progression is a new challenge, and scarce data support it. We aimed to examine the outcomes of mUC patients after progression to ICI, especially when receiving chemotherapy. Methods: Data were retrospectively collected from clinical records of mUC patients whose disease progressed to anti-programmed death 1 (PD-1)or programmed death ligand 1 (PD-L1) therapy at 14 Italian centers. Patients were grouped according to ICI therapy setting into SALVAGE (ie, ICI delivered ⩾ second-line therapy after platinum-based chemotherapy) and NAÏVE (ie, first-line therapy) groups. Progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared among subgroups. Cox regression assessed the effect of treatments after progression to ICI on OS. Objective response rate (ORR) was calculated as the sum of partial and complete radiologic responses. Results: The study population consisted of 201 mUC patients who progressed after ICI: 59 in the NAÏVE cohort and 142 in the SALVAGE cohort. Overall, 52 patients received chemotherapy after ICI progression (25.9%), 20 (9.9%) received ICI beyond progression, 115 (57.2%) received best supportive care only, and 14 (7.0%) received investigational drugs. Objective response rate to chemotherapy in the post-ICI setting was 23.1% (28.0% in the NAÏVE group and 18.5% in the SALVAGE group). Median PFS and OS to chemotherapy after ICI-PD was 5 months (95% confidence interval [CI]: 3-11) and 13 months (95% CI: 7-NA) for the NAÏVE group; 3 months (95% CI: 2-NA) and 9 months (95% CI: 6-NA) for the SALVAGE group, respectively. Overall survival from ICI initiation was 17 months for patients receiving chemotherapy (hazard ratio [HR] = 0.09, p < 0.001), versus 8 months for patients receiving ICI beyond progression (HR = 0.13, p < 0.001), and 2 months for patients who did not receive further active treatment ( p < 0.001). Conclusions: Chemotherapy administered after ICI progression for mUC patients is advisable irrespective of the treatment line.

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“…The study of atezolizumab in locally advanced or metastatic urothelial or non‐urothelial carcinoma of the urinary tract (SAUL study), investigated worldwide safety and efficacy of atezolizumab, enrolled 101 patients with an ECOG PS of 2 and noted an ORR of 5% and median OS of 2.3 months. Barata et al reported a single‐institution series of 79 patients with aUC treated with atezolizumab, including 24% with an ECOG PS ≥ 2, and they reported an ORR for the entire cohort (including an ECOG PS of 0‐1) of 18%. Pal et al reported outcomes from an expanded‐access program with atezolizumab, which included 20 patients with an ECOG PS ≥ 2, and they noted an ORR of 17% among all patients with evaluable disease (including an ECOG PS of 0‐1).…”

Section: Discussionmentioning

confidence: 99%

Impact of performance status on treatment outcomes: A real‐world study of advanced urothelial cancer treated with immune checkpoint inhibitors

Khaki

Diamantopoulos

et al. 2019

Cancer

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Background Immune checkpoint inhibitors (ICIs) represent an appealing treatment for patients with advanced urothelial cancer (aUC) and a poor performance status (PS). However, the benefit of ICIs for patients with a poor PS remains unknown. It was hypothesized that a poor Eastern Cooperative Oncology Group (ECOG) PS (≥2 vs 0‐1) would correlate with shorter overall survival (OS) in patients receiving ICIs. Methods In this retrospective cohort study, clinicopathologic, treatment, and outcome data were collected for patients with aUC who were treated with ICIs at 18 institutions (2013‐2019). The overall response rate (ORR) and OS were compared for patients with an ECOG PS of 0 to 1 and patients with an ECOG PS ≥ 2 at ICI initiation. The association between a new ICI in the last 30 and 90 days of life (DOL) and death location was also tested. Results Of the 519 patients treated with ICIs, 395 and 384 were included in OS and ORR analyses, respectively, with 26% and 24% having a PS ≥ 2. OS was higher in those with a PS of 0 to 1 than those with a PS ≥ 2 who were treated in the first line (median, 15.2 vs 7.2 months; hazard ratio [HR], 0.62; P = .01) but not in subsequent lines (median, 9.8 vs 8.2 months; HR, 0.78; P = .27). ORRs were similar for patients with a PS of 0 to 1 and patients with a PS ≥ 2 in both lines. Of the 288 patients who died, 10% and 32% started ICIs in the last 30 and 90 DOL, respectively. ICI initiation in the last 30 DOL was associated with increased odds of death in a hospital (odds ratio, 2.89; P = .04). Conclusions Despite comparable ORRs, ICIs may not overcome the negative prognostic role of a poor PS, particularly in the first‐line setting, and the initiation of ICIs in the last 30 DOL was associated with hospital death location.

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Atezolizumab in Metastatic Urothelial Carcinoma Outside Clinical Trials: Focus on Efficacy, Safety, and Response to Subsequent Therapies

Abstract: Patients with mUC who progressed on atezolizumab were unlikely to receive subsequent systemic treatments and the benefit of those treatments appeared limited in our cohort. The findings may impact timing and designs of clinical trials in mUC.

Cited by 14 publications

References 35 publications

Pembrolizumab for treating advanced urothelial carcinoma in patients with impaired performance status: Analysis of a Japanese nationwide cohort

Pembrolizumab for treating advanced urothelial carcinoma in patients with impaired performance status: Analysis of a Japanese nationwide cohort

Clinical Outcomes of Patients With Metastatic Urothelial Carcinoma After Progression to Immune Checkpoint Inhibitors: A Retrospective Analysis by the Meet-Uro Group (Meet-URO 1 Study)

Impact of performance status on treatment outcomes: A real‐world study of advanced urothelial cancer treated with immune checkpoint inhibitors

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