Immune checkpoint inhibitors rechallenge in urological tumors: An extensive review of the literature

Bimbatti, Davide; Maruzzo, Marco; Pierantoni, Francesco; Diminutto, Alberto; Dionese, Michele; Deppieri, Filippo Maria; Lai, Eleonora; Zagonel, Vittorina; Basso, Umberto

doi:10.1016/j.critrevonc.2022.103579

Cited by 13 publications

(10 citation statements)

References 81 publications

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“…Little is known about immunotherapy re‐challenge in patients with mUC. 15 One study evaluated 13 patients, including three patients with mUC who stopped anti‐PD‐1 or anti‐programmed death ligand 1 (PD‐L1) therapy in the absence of disease progression. 16 Two of three patients with mUC experienced tumor relapse, and they responded to the same checkpoint inhibitor (one PR and one SD) after treatment‐free periods of 19.5 and 6.5 months, respectively.…”

Section: Discussionmentioning

confidence: 99%

Discontinuation of pembrolizumab for advanced urothelial carcinoma without disease progression: Nationwide cohort study

et al. 2022

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Pembrolizumab, an anti‐programmed death 1 monoclonal antibody, has revolutionized the treatment of metastatic urothelial carcinoma. However, the optimal treatment duration for treatment responders has not been established. To address this, we retrospectively assess the treatment outcomes and duration of pembrolizumab for patients whose best response was complete response (CR) or partial response (PR) in a Japanese nationwide cohort of platinum‐refractory metastatic urothelial carcinoma. Of 203 patients whose best response was CR or PR, 83 patients discontinued pembrolizumab before progression. The median pembrolizumab treatment duration was 6.9 months. The 2‐year relapse‐free survival (RFS), treatment‐free survival, and OS rates after discontinuation were 49.0%, 57.4%, and 74.5%, respectively. CR, higher hemoglobin levels, and a better Eastern Cooperative Oncology Group performance status at the time of discontinuation were associated with significantly better RFS. Pembrolizumab was re‐administered to 12 patients. Pembrolizumab re‐challenge resulted in CR, PR, stable disease, and progressive disease in six, three, two, and one patient, respectively. Propensity score‐matched landmark analysis revealed no significant OS difference between patients who continued or discontinued pembrolizumab at 6, 12, and 18 months ( p = 0.91, 0.99, and 0.25, respectively). Our findings demonstrated that patients with objective responses had favorable survival outcomes and suggested that pembrolizumab could be discontinued safely in this population. This study should drive further efforts to optimize the treatment duration for pembrolizumab responders.

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Section: Discussionmentioning

confidence: 99%

Discontinuation of pembrolizumab for advanced urothelial carcinoma without disease progression: Nationwide cohort study

et al. 2022

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“…If articles matched all the following criteria, they were included ( Sung et al, 2021 ). patients diagnosed with urological cancers ( Niu et al, 2021 ); patients treated with ICIs ( Bimbatti et al, 2022 ); patients separated into the antacid use group and non-antacid use group ( Kim et al, 2020 ); provided at least one of the outcomes of interest [multivariable/adjusted overall survival (OS), progression-free survival (PFS), and objective response rate (ORR)]. For retrospective studies, the results of univariable analysis are vulnerable to confounding factors, so we included studies that provided multivariable analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Chen Shi, Huazhong University of Science and Technology, China of immune checkpoint inhibitors (ICIs) has transformed the treatment of a variety of cancers, including urological malignancies. These antibodies act by blocking the checkpoint pathways, which are physiologic mechanisms established to switch off the immune response and prevent autoimmunity (Bimbatti et al, 2022).…”

Section: Open Access Edited Bymentioning

confidence: 99%

Effects of PPIs use on clinical outcomes of urothelial cancer patients receiving immune checkpoint inhibitor therapy

et al. 2022

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Objective: Immune checkpoint inhibitors (ICIs) have recently demonstrated promising performance in improving the prognosis of urological cancer patients. The goal of this meta-analysis was to determine the impact of PPI use on the clinical outcomes of urological cancer patients receiving ICI therapy.Methods: Before 6 May 2022, the eligible literature was searched using PubMed, EMBASE, Cochrane Library, and Google Scholar. The clinical outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).Results: A total of six articles met the inclusion criteria, and of the 1980 patients with advanced or metastatic urothelial cancers (UC) included. The meta-analysis displayed that PPI use could increase the risk of progression by 50.7% (HR: 1.507, 95% CI: 1.327–1.711, p < 0.001) and death by 58.7% (HR: 1.587, 95% CI: 1.367–1.842, p < 0.001), and reduce the ORR (OR: 0.503, 95% CI: 0.360–0.703, p < 0.001) in UC patients receiving ICIs. No significant heterogeneity and publication bias existed. Sensitivity analysis proved that the results were stable and reliable.Conclusion: The meta-analysis indicated that concomitant PPI use was significantly associated with low clinical benefit in UC patients.

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“…A literature review [ 71 ] focusing on the feasibility, safety, timing, and efficacy of ICI rechallenge in genitourinary cancers showed there is limited data. The study categorized the various ICI retreatment strategies into three main clinical scenarios: retreatment after discontinuing a prior course of ICI while on response; retreatment after an interruption due to IRAEs; and retreatment after progression while on ICI therapy.…”

Section: Main Findings Of the Literature (Review) Questmentioning

confidence: 99%

Intra-Abdominal Malignant Melanoma: Challenging Aspects of Epidemiology, Clinical and Paraclinical Diagnosis and Optimal Treatment—A Literature Review

et al. 2022

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According to European consensus-based interdisciplinary guidelines for melanoma, cutaneous melanoma (CM) is the most deadly form of dermatological malignancy, accounting for 90% of the deaths of skin cancer patients. In addition to cutaneous melanoma, mucosal melanoma occurs in four major anatomical sites, including the upper respiratory tract, the conjunctiva, the anorectal region, and the urogenital area. As this cancer type metastasizes, a classification used in the current medical literature is the distinction between secondary lesions and primary malignant melanoma of the abdominal cavity. Given that malignant melanoma is the most common cancer that spreads to the gastrointestinal tract, different imaging modalities compete to diagnose the phenomenon correctly and to measure its extension. Treatment is primarily surgery-based, supported by immunotherapy, and prolongs survival, even when performed at stage IV illness. In the end, special forms of malignant melanoma are discussed, such as melanoma of the genito-urinary tract and amelanotic/achromic melanoma. The importance of this present literature review relies on yielding and grouping consistent and relevant, updated information on the many aspects and challenges that a clinician might encounter during the diagnosis and treatment of a patient with intra-abdominal melanoma.

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Immune checkpoint inhibitors rechallenge in urological tumors: An extensive review of the literature

Cited by 13 publications

References 81 publications

Discontinuation of pembrolizumab for advanced urothelial carcinoma without disease progression: Nationwide cohort study

Discontinuation of pembrolizumab for advanced urothelial carcinoma without disease progression: Nationwide cohort study

Effects of PPIs use on clinical outcomes of urothelial cancer patients receiving immune checkpoint inhibitor therapy

Intra-Abdominal Malignant Melanoma: Challenging Aspects of Epidemiology, Clinical and Paraclinical Diagnosis and Optimal Treatment—A Literature Review

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