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

Ito, Katsuhiro; Kobayashi, Takashi; Kojima, Takahiro; Hikami, Kensuke; Yamada, Takeshi; Ogawa, Kosuke; Nakamura, Kenji; Sassa, Naoto; Yokomizo, Akira; Abe, Takashige; Tsuchihashi, Kazunari; Tatarano, Shuichi; Inokuchi, Junichi; Tomida, Ryotaro; Fujiwara, Maki; Takahashi, Atsushi; Matsumoto, Kazumasa; Shimizu, Kosuke; Araki, Hiromasa; Kurahashi, Ryoma; Yu, Osaki; Tashiro, Yu; Uegaki, Masayuki; Ogawa, Osamu; Kitamura, Hiroshi; Nishiyama, Hiroyuki

doi:10.1002/cam4.3863

Cited by 17 publications

(20 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With regard to the real‐world practice and treatment of older patients or those with impaired PS, pembrolizumab treatment showed comparable oncological outcomes and safety profiles in older patients 5 and in a subset of patients with poor PS 6 . Real‐world data regarding the outcome of EV treatment in patients who are ineligible for clinical trials will be warranted in the future.…”

Section: Discussionmentioning

confidence: 99%

Clinical practice pattern in patients with advanced urothelial cancer who had progressed on pembrolizumab in the pre‐enfortumab vedotin era

et al. 2022

Self Cite

View full text Add to dashboard Cite

Objectives: Pembrolizumab, an anti-PD-1 monoclonal antibody, revolutionized the treatment for advanced urothelial carcinoma. However, the standard treatment for patients after disease progression with pembrolizumab had not been established until the recent approval of enfortumab vedotin. We analyzed the treatment of these patients in the real world, and the patient background and outcomes. Methods: We extracted data from 543 patients who experienced progressive disease after pembrolizumab initiation from a Japanese nation-wide cohort of platinumrefractory, metastatic urothelial carcinoma. Results: The median overall survival of the 543 patients was 3.5 months (95% confidence interval 3.0-4.1). Of these, only 20.6% (n = 112) received chemotherapy as a subsequent systemic treatment after progressive disease. The regimen of chemotherapy was very diverse. The median overall survival was 11.9 months (95% confidence interval 9.2-14.7) for patients who received chemotherapy, compared to 2.4 months for those who did not receive chemotherapy (95% confidence interval 2.1-2.9; P < 0.0001). Patients who received subsequent chemotherapy were more likely to have better performance status, neutrophil-to-lymphocyte ratio <3, hemoglobin >11 mg/dL, and history of a single chemotherapeutic regimen at pembrolizumab initiation. Conclusions: This report highlights the real-world practice of the management after pembrolizumab treatment failure in the pre-enfortumab vedotin era, characterized by infrequent use of subsequent anticancer therapy comprising various regimens, reflecting the lack of a standard treatment. Clinical introduction of enfortumab vedotin is expected to improve treatment outcomes in this setting. The present study will provide important baseline data for evaluating the influence of enfortumab vedotin on clinical practices and outcomes.

show abstract

Section: Discussionmentioning

confidence: 99%

Clinical practice pattern in patients with advanced urothelial cancer who had progressed on pembrolizumab in the pre‐enfortumab vedotin era

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…After stratifying patients on the basis of the occurrence of clinically significant irAEs, 198 patients were extracted from each group by PSM and included in further analyses. Baseline characteristics were well balanced between the groups (Table 1 7 [4][5][6][7][8][9][10][11][12][13][14][15][16], p = 0.773). Multivariate analysis illustrated that the presence of grade ≥2 irAEs was associated with significantly longer PFS (HR = 0.48, 95% CI = 0.31-0.73, p < 0.001) and a trend toward favorable OS (HR = 0.71, 95% CI = 0.48-1.03, p = 0.070; Figure S1).…”

Section: Occurrence Of Clinically Significant Iraes and Efficacymentioning

confidence: 94%

“…However, the number of responders to ICIs is limited, and biomarkers for predicting ICI efficacy are lacking. In addition to oncological features such as a microsatellite instability–high status and programmed death ligand 1 (PD‐L1) expression, clinical features including the performance status (PS) and neutrophil‐to‐lymphocyte ratio (NLR) were previously studied as biomarkers 8–10 . Recently, an association between the onset of irAEs and the therapeutic efficacy of ICIs was suggested in melanoma and non–small cell lung cancer (NSCLC) 11–13 .…”

Section: Introductionmentioning

confidence: 99%

Immune‐related adverse events in urothelial cancer patients: Adjustment for immortal time bias

et al. 2022

Self Cite

View full text Add to dashboard Cite

To investigate the association between the onset, severity, and type of immune‐related adverse events (irAEs) and the efficacy of pembrolizumab in patients with platinum‐pretreated advanced urothelial carcinoma (UC), we retrospectively collected clinical datasets of 755 patients and conducted landmark analysis. Patients who survived for fewer than 3 months were excluded from the evaluation to reduce the immortal time bias. In total, 620 patients were evaluated, of whom 220 patients (35.5%) experienced grade ≥2 irAEs, including 134 patients with grade 2 irAEs and 86 with grade ≥3 irAEs. Propensity score matching extracted 198 patients with and without grade ≥2 irAEs. The onset of grade ≥2 irAEs was associated with longer median progression‐free survival (PFS) (8.3 months vs. 4.5 months, p = 0.003) and overall survival (OS) (20.4 months vs. 14.3 months, p = 0.031) and a higher objective response rate (ORR) (44.8% vs. 30.2%, p = 0.004). Patients with grade 2 irAEs had significantly better oncological outcomes (PFS, OS, and ORR) than grade ≤1 and ≥3 irAEs. Patients with grade ≥3 irAEs had worse outcomes than grade 2 irAEs. Endocrine and skin irAEs were related with better survival outcomes, and the rate of severities was lower in these categories. In conclusion, the occurrence of irAEs, particularly low‐grade irAEs, was predictive of pembrolizumab efficacy in patients with platinum‐pretreated advanced UC.

show abstract

“… 4 , 5 , 6 Systemic chemotherapy and ICIs are two immunoregulation agents frequently administered to patients with advanced UC. 7 , 8 , 9 , 10 , 11 , 12 Treatment with ICIs in combination or ICIs plus TKIs is considered the standard of care for patients with metastatic RCC. 13 , 14 , 15 , 16 , 17 , 18 Furthermore, immune‐related AEs are closely associated with high‐dose steroid administration in patients treated with ICIs, and steroid use has been associated with impaired humoral response to SARS‐CoV‐2 mRNA vaccines in patients with cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the seropositivity rate in patients with solid tumors was reported as slightly lower (approximately 90%) than in healthy controls 4–6 . Systemic chemotherapy and ICIs are two immunoregulation agents frequently administered to patients with advanced UC 7–12 . Treatment with ICIs in combination or ICIs plus TKIs is considered the standard of care for patients with metastatic RCC 13–18 .…”

Section: Introductionmentioning

confidence: 99%

Effect of active anticancer therapy on serologic response to SARS‐CoV‐2 BNT162b2 vaccine in patients with urothelial and renal cell carcinoma

et al. 2022

View full text Add to dashboard Cite

Objectives To evaluate the serologic response to the BNT162b2 messenger ribonucleic acid vaccine in patients with urothelial carcinoma and renal cell carcinoma. Methods Between June 2021 and November 2021, we retrospectively evaluated blood samples from 60 healthy controls (control group), 57 patients with urothelial carcinoma, and 28 patients with renal cell carcinoma who had received two doses of the BNT162b2 vaccine at Hirosaki University Hospital. We determined the immunoglobulin G antibody titers against the severe acute respiratory syndrome coronavirus 2 spike receptor‐binding domain. Seropositivity was defined as ≥15 U/mL. We investigate factors associated with antibody titers and seropositivity in the patients with urothelial carcinoma and renal cell carcinoma. Results Antibody titers in the control, urothelial carcinoma, and renal cell carcinoma groups were 813, 431, and 500 U/mL, respectively. Seropositivity was 100%, 90%, and 96% in the control, urothelial carcinoma, and renal cell carcinoma groups, respectively. Of the 85 patients, 37 of 57 (65%) and 21 of 28 (75%) were actively undergoing anticancer treatment for urothelial carcinoma and renal cell carcinoma, respectively. Anti‐severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers and seropositivity was not significantly different between the patients with urothelial carcinoma and renal cell carcinoma. Anti‐severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers were not significantly associated with active anticancer therapy or steroid treatment for immune‐related adverse events. Univariable logistic regression analysis revealed that older age and metastatic disease were significantly and negatively associated with seropositivity. Conclusions Patients with urothelial carcinoma or renal cell carcinoma exhibited an adequate antibody response to the BNT162b2 vaccine. Active anticancer therapy was not significantly associated with seropositivity following vaccination with severe acute respiratory syndrome coronavirus 2 BNT162b2 in patients with urothelial carcinoma and renal cell carcinoma.

show abstract

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

Cited by 17 publications

References 22 publications

Clinical practice pattern in patients with advanced urothelial cancer who had progressed on pembrolizumab in the pre‐enfortumab vedotin era

Clinical practice pattern in patients with advanced urothelial cancer who had progressed on pembrolizumab in the pre‐enfortumab vedotin era

Immune‐related adverse events in urothelial cancer patients: Adjustment for immortal time bias

Effect of active anticancer therapy on serologic response to SARS‐CoV‐2 BNT162b2 vaccine in patients with urothelial and renal cell carcinoma

Contact Info

Product

Resources

About