Clinical benefit of continuing pembrolizumab treatment beyond progression in patients with metastatic urothelial carcinoma

Fukuokaya, Wataru; Kimura, Takahiro; Yanagisawa, Takafumi; Kimura, Shoji; Tsuzuki, Shunsuke; Koike, Yuhei; Iwamoto, Yuya; Enei, Yuki; Tanaka, Masatoshi; Urabe, Fumihiko; Onuma, Hajime; Honda, Minoru; Miki, Jun; Oyama, Yu; Abe, Hirokazu; Egawa, Shin

doi:10.1007/s00262-021-02980-x

Cited by 8 publications

(10 citation statements)

References 28 publications

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“…This study concluded that pembrolizumab maintained clinically meaningful OS benefits in patients with locally advanced or mUC who progressed during or after platinum-based chemotherapy [ 23 ]. Fukuokaya et al reported that the median OS was significantly longer in the continuation group than in the discontinuation of pembrolizumab group (17.8 vs. 8.8 months; p = 0.038) [ 18 ]. In the multivariate Cox regression model, continued pembrolizumab administration and longer duration of pembrolizumab treatment beyond progression were independently associated with a reduced risk of all-cause mortality [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Fukuokaya et al reported that the median OS was significantly longer in the continuation group than in the discontinuation of pembrolizumab group (17.8 vs. 8.8 months; p = 0.038) [ 18 ]. In the multivariate Cox regression model, continued pembrolizumab administration and longer duration of pembrolizumab treatment beyond progression were independently associated with a reduced risk of all-cause mortality [ 18 ]. These results suggest that the oncological outcomes of patients with mUC who received pembrolizumab as second-line treatment are not necessarily acceptable.…”

Section: Discussionmentioning

confidence: 99%

“…In recent studies, neutrophil-to-lymphocyte ratio (NLR) [ 12 ], psoas muscle mass index (PMI) [ 13 ], albumin-to-globulin ratio (AGR) [ 14 ], C-reactive protein (CRP) flare response [ 15 ], poor Eastern Cooperative Oncology Group performance status (ECOG-PS) [ 16 ], number of metastatic sites, and an early increase in NLR [ 17 ] have been useful predictive markers for oncological outcomes in patients with mUC treated with pembrolizumab [ 12 , 13 , 14 , 15 , 16 , 17 ]. Fukuokaya et al reported that continuous administration of pembrolizumab until disease progression may improve OS in patients with mUC [ 18 ]. However, the number of patients with mUC enrolled in these studies was relatively small.…”

Section: Introductionmentioning

confidence: 99%

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The Impact of Neutrophil-to-Lymphocyte Ratio after Two Courses of Pembrolizumab for Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma

et al. 2022

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We focused on the therapeutic effect of pembrolizumab for metastatic urothelial carcinoma (mUC) and evaluated predictive factors for improving clinical outcomes. We conducted a retrospective multicenter cohort study of patients with mUC who received pembrolizumab. The endpoint was to evaluate the association between clinicopathological features and oncological outcomes. A total of 160 patients were enrolled in this study and were divided into two groups: the responder and the non-responder group, according to the best response. They were followed up for a median period of 10 months. The median overall (OS) and progression-free survival (PFS) in this study were 17 and 4 months, respectively. The responder group did not achieve median OS and it was 10 months in the non-responder group (p < 0.001). Similarly, the responder group did not achieve PFS, and it was 2 months in the non-responder group (p < 0.001). Regarding the neutrophil-to-lymphocyte ratio (NLR) after two courses of administration of pembrolizumab, patients with NLR < 3.24 had significantly better oncological outcomes than those with NLR ≥ 3.24. Multivariate analysis showed a significant association between NLR after two courses of pembrolizumab and OS. Therefore, the absolute value of NLR after two courses of pembrolizumab was a significant predictive factor for oncological outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Impact of Neutrophil-to-Lymphocyte Ratio after Two Courses of Pembrolizumab for Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma

et al. 2022

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“…However, the continuation of pembrolizumab administration beyond progression might be beneficial in patients with metastatic UC who were clinically stable [ 21 ].…”

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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“…Previous study reported that some patients might benefit from rechallenge of immunotherapy beyond Response Evaluation Criteria in Solid Tumors (RECIST)1.1-defined progression ( Chiou and Burotto, 2015 ). It was documented that rechallenge of immunotherapy beyond progression (RIBP) was effective for advanced renal cell carcinoma, squamous cell carcinoma of the head and neck, melanoma, NSCLC, and urothelial carcinoma ( George et al, 2016 ; Escudier et al, 2017 ; Long et al, 2017 ; Gandara et al, 2018a ; Beaver et al, 2018 ; Haddad et al, 2019 ; Fukuokaya et al, 2021 ). For instance, in a subgroup analysis of Checkmate025 study, patients with advanced renal cell carcinoma in the RIBP group had a significantly longer post-progression OS than those in the discontinuation of immunotherapy beyond progression (DIBP) group ( Escudier et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Rechallenge of immunotherapy beyond progression in patients with extensive-stage small-cell lung cancer

Liu

et al. 2022

Front. Pharmacol.

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Background: Rechallenge of immunotherapy beyond progression (RIBP) has been demonstrably effective in a variety of cancers. Our study aims to investigate the efficacy of RIBP in small-cell lung cancer (SCLC) patients under real-world conditions.Methods: SCLC patients who experienced progressive disease after receiving programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors combined with chemotherapy from January 2017 to October 2021 were enrolled. The study population was divided into two groups: the RIBP group and the discontinuation of immunotherapy beyond progression (DIBP) group. Inverse propensity score weighting (IPSW) method was used to balance the clinical baseline characteristics. The short-term and long-term efficacy of the two groups was compared.Results: 100 SCLC patients were included in this study. There were 45 patients in the RIBP group and 55 patients in the DIBP group. The disease control rate (DCR) and the proportion of durable clinical benefit (DCB) were significantly higher in the RIBP group (DCR: 79.7% vs. 55.7%, p = 0.027; DCB: 40.7 vs. 20.7%, p = 0.025) after weighting. The median progressive-free survival (PFS) in the RIBP group was significantly longer than the DIBP group in the total population (mPFS: 4.8 vs. 2.4 months, p = 0.002), while there was no significant difference in overall survival (OS) of the two groups (mOS: 17.4 vs. 8.0 months, p = 0.098). In the weighted first-line initial immunotherapy subgroup, PFS and OS were significantly improved in the RIBP group (mPFS: 4.5 vs. 2.8 months, p = 0.017; mOS: 11.6 vs. 5.4 months, p = 0.028). After weighting, the RIBP group had a significantly longer PFS than the DIBP group in the SD/PD response to the initial immunotherapy subgroup (mPFS: 6.8 vs. 1.8 months, p = 0.026).Conclusion: Rechallenge of PD-1/PD-L1 inhibitors could bring benefits to SCLC patients, especially in the first-line initial immunotherapy subgroup or SD/PD response to the initial immunotherapy subgroup.

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Clinical benefit of continuing pembrolizumab treatment beyond progression in patients with metastatic urothelial carcinoma

Cited by 8 publications

References 28 publications

The Impact of Neutrophil-to-Lymphocyte Ratio after Two Courses of Pembrolizumab for Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma

The Impact of Neutrophil-to-Lymphocyte Ratio after Two Courses of Pembrolizumab for Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma

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

Rechallenge of immunotherapy beyond progression in patients with extensive-stage small-cell lung cancer

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