Immune-checkpoint inhibitors and metastatic prostate cancer therapy: Learning by making mistakes

2020 ◽  
Vol 88 ◽  
pp. 102057 ◽  
Author(s):  
Mélanie Claps ◽  
Alessia Mennitto ◽  
Valentina Guadalupi ◽  
Pierangela Sepe ◽  
Marco Stellato ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Metastatic Prostate Cancer ◽  
Checkpoint Inhibitors ◽  
Prostate Cancer Therapy

scholarly journals Oncological Response and Predictive Biomarkers for the Checkpoint Inhibitors in Castration-Resistant Metastatic Prostate Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 (1) ◽  
pp. 8
Author(s):  
Omar Fahmy ◽  
Nabil A. Alhakamy ◽  
Mohd G. Khairul-Asri ◽  
Osama A. A. Ahmed ◽  
Usama A. Fahmy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Metastatic Prostate Cancer ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Castration Resistant Prostate Cancer ◽  
Overall Response ◽  
Castration Resistant

Recently, checkpoint inhibitors have been investigated in metastatic prostate cancer, however their overall effect is unclear and needs to be further investigated. Objectives: The aim of this systematic review is to investigate the oncological response of metastatic castration-resistant prostate cancer patients to immune checkpoint inhibitors. Methods: Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, a systematic review of the literature was conducted through online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. Eligible publications were selected after a staged screening and selection process. RevMan 5.4 software was employed to run the quantitative analysis and forest plots. Risk of bias assessment was conducted using the Cochrane tool and Newcastle–Ottawa Scale for the randomized and non-randomized trials, respectively. Results: From the 831 results retrieved, 8 studies including 2768 patients were included. There was no significant effect on overall survival (OS) (overall response (OR) = 0.98; Z = 0.42; p = 0.67). Meanwhile, progression-free survival (PFS) was significantly better with immune checkpoint inhibitors administration (OR = 0.85; Z = 3.9; p < 0.0001). The subgroup analysis for oncological outcomes based on programmed death ligand 1 (PD-L1) positivity status displayed no significant effect, except on prostate-specific antigen response rate (PSA RR) (OR = 3.25; Z = 2.29; p = 0.02). Based on DNA damage repair (DDR), positive patients had a significantly better PFS and a trend towards better OS and overall response rate (ORR); the ORR was 40% in positive patients compared to 20% in the negative patients (OR = 2.46; Z = 1.3; p = 0.19), while PSA RR was 23.5% compared to 14.3% (OR = 1.88; Z = 0.88; p = 0.38). Better PFS was clearly associated with DDR positivity (OR = 0.70; Z = 2.48; p = 0.01) with a trend towards better OS in DDR positive patients (OR = 0.71; Z = 1.38; p = 0.17). Based on tumor mutation burden (TMB), ORR was 46.7% with high TMB versus 8.8% in patients with low TMB (OR = 11.88; Z = 3.0; p = 0.003). Conclusions: Checkpoint inhibitors provide modest oncological advantages in metastatic castration-resistant prostate cancer. There are currently no good predictive indicators that indicate a greater response in some patients.

The Current Role of Immunotherapy in mCRPC: A Systematic Review

2021 ◽  
Vol 8 (7) ◽  
Author(s):  
Dalibey H ◽  
◽  
Hansen TF ◽  
Zedan AH ◽  
◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Specific Antigen ◽  
Treatment Modalities ◽  
Significant Difference

Background: The development of immunotherapy has shown promising results in several malignant diseases, including prostate cancer, calling for a systematic review of the current literature. This review aims to evaluate the present data and prospects of immune checkpoint inhibitors in metastatic Castration Resistant Prostate Cancer (mCRPC). Methods: Articles were identified via a systematic search of the electronic database Pubmed, in accordance with the PICO process and following the PRISMA guidelines. Articles in English studying immune checkpoint inhibitors in patients with mCRPC published between March 2010 and March 2020 were eligible for inclusion. Endpoints of interest were Overall Survival (OS), Progression-Free Survival (PFS), clinical Overall Response Rate (ORR), and Prostate-Specific Antigen (PSA) response rate. Results: Ten articles were identified as eligible for inclusion. The studies primarily explored the use of Ipilimumab, a CTLA-4 inhibitor, and Pembrolizumab, a PD-1 inhibitor. These drugs were both used either as monotherapy or in combination with other treatment modalities. The largest trial included in the review demonstrated no significant difference in overall survival between the intervention and placebo. However, two studies presented promising data combing immunotherapy and immune vaccines. Grade 3 and 4 adverse events ranging from 10.1% to 82.3%, whit diarrhea, rash, and fatigue were the most frequently reported. Forty relevant ongoing trials were identified exploring immunotherapy with or without a parallel treatment modality. Conclusion: Overall, the current data shows that the effect of immune checkpoint inhibitors as monotherapy may have limited impact on mCRPC, and the results from ongoing combinational trials are eagerly awaited.

scholarly journals The role of immune checkpoint inhibitors in prostate cancer

2019 ◽  
Vol 26 (1) ◽  
pp. 120-124
Author(s):  
Gabriel Surdacki ◽  
Aneta Szudy-Szczyrek ◽  
Aneta Gorący ◽  
Katarzyna Chyl-Surdacka ◽  
Marek Hus
Keyword(s):  
Prostate Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

Immune Checkpoint Inhibitors for Cancer Therapy in the COVID-19 Era

2020 ◽  
Vol 26 (16) ◽  
pp. 4201-4205 ◽  
Author(s):  
Michele Maio ◽  
Omid Hamid ◽  
James Larkin ◽  
Alessia Covre ◽  
Maresa Altomonte ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

Combination of a therapeutic cancer vaccine and immune checkpoint inhibitors in prostate cancer.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 5084-5084 ◽  
Author(s):  
Ravi Amrit Madan ◽  
Marijo Bilusic ◽  
Julius Strauss ◽  
Fatima Karzai ◽  
Lisa M. Cordes ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Vaccine ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Therapeutic Cancer Vaccine

scholarly journals Combining Immune Checkpoint Inhibitors With Conventional Cancer Therapy

2018 ◽  
Vol 9 ◽  
Author(s):  
Yiyi Yan ◽  
Anagha Bangalore Kumar ◽  
Heidi Finnes ◽  
Svetomir N. Markovic ◽  
Sean Park ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

A multidisciplinary approach to toxicity management of modern immune checkpoint inhibitors in cancer therapy

2016 ◽  
Vol 26 (5) ◽  
pp. 469-480 ◽  
Author(s):  
Lisa Kottschade ◽  
Adam Brys ◽  
Tobias Peikert ◽  
Mabel Ryder ◽  
Laura Raffals ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Multidisciplinary Approach ◽  
Checkpoint Inhibitors

scholarly journals Combination of Immune Checkpoint Inhibitors and Radiotherapy for Advanced Non-Small-Cell Lung Cancer and Prostate Cancer: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zexi Xu ◽  
Jia Feng ◽  
Yiming Weng ◽  
Yao Jin ◽  
Min Peng
Keyword(s):  
Prostate Cancer ◽  
Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Fixed Effects ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Clinical Manifestations ◽  
Grade 3

Objectives. Immune checkpoint inhibitors (ICI) combined with radiotherapy (RT) have emerged as a breakthrough therapy in the treatment of various cancers. The combination has a strong rationale, but data on their efficacy and safety are still limited. Hence, we comprehensively searched the database and performed this study to elucidate the clinical manifestations of this combined strategy. Methods. We performed a meta-analysis of randomized trials that compared ICI plus RT with placebo plus RT or ICI alone for the treatment of advanced nonsmall-cell lung cancer (NSCLC) and prostate cancer. The outcomes included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and treatment-related adverse events. A fixed-effects or random-effects model was adopted depending on between-study heterogeneity. Results. Three trials involving 1584 patients were included. ICI plus RT was significantly associated with improvement of OS (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.70–0.94, P = 0.004 ), PFS (HR = 0.64; 95% CI 0.56–0.72, P < 0.00001 ), and DCR (relative risk [RR] = 1.38; 95% CI 1.03–1.84, P = 0.03 ). A significant predictor for PFS with the combination of ICI and RT was age, as a significant improvement in PFS (HR = 0.49; 95% CI 0.37–0.64, P < 0.00001 ) was observed in NSCLC patients aged under 65 years. In safety analyses, patients receiving ICI plus RT had a significantly higher incidence of dyspnea (RR = 2.43; 95% CI 1.16–5.08, P = 0.02 ) and pneumonitis of grade 3 or higher (RR = 2.78; 95% CI 1.32–5.85, P = 0.007 ). Conclusion. The combination of ICI and RT was associated with improved OS, PFS, and DCR. Patients under 65 years will be the dominant beneficiaries. However, the incidence of dyspnea and pneumonia of grade 3 or higher also increased, which deserves our vigilance.

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