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Progression in immunotherapy for advanced prostate cancer.

ABSTRACT: Prostate cancer is one of the most common malignant cancers of the male genitourinary system and has high morbidity and mortality. Currently, treatment modalities for localized prostate cancer focus mainly on radical prostatectomy or radical radiation therapy. Some patients still experience disease recurrence or progression after these treatments, while others are already at an advanced stage or have metastases at the time of diagnosis. With the continuous development and progress of medicine in recent years, immunotherapy has become a revolutionary cancer treatment, and has achieved remarkable accomplishments in the treatment of hematologic malignancies. A variety of immunotherapies have also appeared in the field of advanced prostate cancer treatment, including therapeutic vaccines and immune checkpoint therapies. Despite the discrepancy between the results of some immunotherapy studies, immunotherapy for prostate cancer has shown some initial success, especially in combination immunotherapies. Currently, immunotherapy is mainly used in advanced prostate cancer, especially in patients with metastatic castration-resistant prostate cancer. However, with the development of more clinical trials of immunotherapy, more evidence will be provided supporting the rational application of immunotherapy in the future.

SUBMITTER: Liang H

PROVIDER: S-EPMC10011447 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Progression in immunotherapy for advanced prostate cancer.

Liang Hao H Liu Yang Y Guo Jiao J Dou Maoyang M Zhang Xiaoyi X Hu Liyong L Chen Jun J

Frontiers in oncology 20230228

Prostate cancer is one of the most common malignant cancers of the male genitourinary system and has high morbidity and mortality. Currently, treatment modalities for localized prostate cancer focus mainly on radical prostatectomy or radical radiation therapy. Some patients still experience disease recurrence or progression after these treatments, while others are already at an advanced stage or have metastases at the time of diagnosis. With the continuous development and progress of medicine in ...[more]

PMID: 36925917

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Project description:BackgroundImmune checkpoint inhibitors (ICIs) represent a great breakthrough in the treatment of advanced non-small cell lung cancer (aNSCLC). However, whether immunotherapy beyond progression (IBP) is effective for aNSCLC has yet to be established. Therefore, a retrospective clinical study was conducted to investigate the efficacy of IBP in patients with aNSCLC under real-world conditions.MethodsA total of 125 Chinese patients with aNSCLC who experienced progressive disease (PD) after receiving monotherapy or combination therapy (combined with chemotherapy or/and antiangiogenic therapy) with programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors between January 2015 and March 2019 were enrolled. Patients who were treated with ICIs for more than 6 weeks after PD were defined as IBP (n=39), while those who received ICI treatment for less than 6 weeks or discontinued it due to PD were defined as non-IBP (n=86). Patient clinical characteristics were evaluated. An optimization-based method was applied to balance the clinical baseline characteristics between the two groups.ResultsIn total population, the IBP group had longer overall survival (median OS, 26.6 vs. 9.5 months; HR, 0.40; 95% CI: 0.23-0.69; P<0.001) and progression-free survival (median PFS, 8.9 vs. 4.1 months; HR, 0.41; 95% CI: 0.26-0.65; P<0.001), compared with the non-IBP group. Despite no significant difference in objective response rate (ORR, 15.4% vs. 11.6%, P=0.560), disease control rate (DCR) was significantly higher in the IBP group (89.7% vs. 61.6%, P<0.001). After balancing baseline covariates, the IBP group also had longer OS (median: 26.6 vs. 10.7 months; HR, 0.40; 95% CI: 0.19-0.84; P=0.015) and PFS (median: 9.7 vs. 4.3 months; HR, 0.28; 95% CI: 0.15-0.51; P<0.001), with a benefit in either of patients previously treated with ICI monotherapy or in combination therapy and with non-response to the previously ICI.ConclusionsIBP is associated with longer OS and PFS in patients with aNSCLC. Our findings may suggest new therapeutic options for patients with aNSCLC who experienced disease progression after initial immunotherapy.

Project description:BackgroundGenomic copy number alterations commonly occur in prostate cancer and are one measure of genomic instability. The clinical implication of copy number change in advanced prostate cancer, which defines a wide spectrum of disease from high-risk localised to metastatic, is unknown.MethodsWe performed copy number profiling on 688 tumour regions from 300 patients, who presented with advanced prostate cancer prior to the start of long-term androgen deprivation therapy (ADT), in the control arm of the prospective randomised STAMPEDE trial. Patients were categorised into metastatic states as follows; high-risk non-metastatic with or without local lymph node involvement, or metastatic low/high volume. We followed up patients for a median of 7 years. Univariable and multivariable Cox survival models were fitted to estimate the association between the burden of copy number alteration as a continuous variable and the hazard of death or disease progression.ResultsThe burden of copy number alterations positively associated with radiologically evident distant metastases at diagnosis (P=0.00006) and showed a non-linear relationship with clinical outcome on univariable and multivariable analysis, characterised by a sharp increase in the relative risk of progression (P=0.003) and death (P=0.045) for each unit increase, stabilising into more modest increases with higher copy number burdens. This association between copy number burden and outcome was similar in each metastatic state. Copy number loss occurred significantly more frequently than gain at the lowest copy number burden quartile (q=4.1 × 10-6). Loss of segments in chromosome 5q21-22 and gains at 8q21-24, respectively including CHD1 and cMYC occurred more frequently in cases with higher copy number alteration (for either region: Kolmogorov-Smirnov distance, 0.5; adjusted P<0.0001). Copy number alterations showed variability across tumour regions in the same prostate. This variance associated with increased risk of distant metastases (Kruskal-Wallis test P=0.037).ConclusionsCopy number alteration in advanced prostate cancer associates with increased risk of metastases at diagnosis. Accumulation of a limited number of copy number alterations associates with most of the increased risk of disease progression and death. The increased likelihood of involvement of specific segments in high copy number alteration burden cancers may suggest an order underlying the accumulation of copy number changes.Trial registrationClinicalTrials.gov NCT00268476 , registered on December 22, 2005. EudraCT 2004-000193-31 , registered on October 4, 2004.

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Progression in immunotherapy for advanced prostate cancer.

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Progression in immunotherapy for advanced prostate cancer.

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