Predictive Genomic Biomarkers of Hormonal Therapy Versus Chemotherapy Benefit in Metastatic Castration-resistant Prostate Cancer

Graf, Ryon P.; Fisher, Virginia; Mateo, Joaquín; Gjoerup, Ole; Madison, Russell; Raskina, Kira; Tukachinsky, Hanna; Creeden, James; Cunningham, Rachel; Huang, Richard S.P.; Mata, Douglas A.; Ross, Jeffrey S.; Oxnard, Geoffrey R.; Venstrom, Jeffrey M.; Zurita, Amado J.

doi:10.1016/j.eururo.2021.09.030

Cited by 18 publications

(19 citation statements)

References 38 publications

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“…Despite advances in the treatments of cancer, there remain a significant proportion of people who do not benefit from them. This conundrum underlines the need to comprehensively understand the pathways that lead to the development of tumours [ 27 ]. Therefore, it is necessary to identify additional targets and biomarkers that could be used in the diagnosis and treatment of cancer [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

A Pan-Cancer Analysis of Heat-Shock Protein 90 Beta1(HSP90B1) in Human Tumours

Wang

2022

Biomolecules

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Background: HSP90B1, a member of the heat-shock protein 90 family, plays a vital role as a molecular chaperone for oncogenes and stimulates tumour growth. However, its role in various cancers remains unexplored. Methods: Using the cancer genome atlas, gene expression omnibus the Human Protein Atlas databases and various other bioinformatic tools, this study investigated the involvement of HSP90B1 in 33 different tumour types. Results: The over-expression of HSP90B1 generally predicted poor overall survival and disease-free survival for patients with tumours, such as adrenocortical carcinoma, bladder urothelial carcinoma, kidney renal papillary cell carcinoma, and lung adenocarcinoma. In this study, HSP90B1 was highly expressed in the majority of tumours. A comparison was made between the phosphorylation of HSP90B1 in normal and primary tumour tissues, and putative functional mechanisms in HSP90B1-mediated oncogenesis were investigated. Additionally, the mutation burden of HSP90B1 in cancer was evaluated along with the survival rate of patients with cancer patients. Conclusion: This first pan-cancer investigation reveals the oncogenic functions of HSP90B1 in various cancers.

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Section: Discussionmentioning

confidence: 99%

A Pan-Cancer Analysis of Heat-Shock Protein 90 Beta1(HSP90B1) in Human Tumours

Wang

2022

Biomolecules

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“…5 However, It is unclear which patients would truly benefit from upfront therapy, and further stratification beyond existing tumor burden and risk classifications is warranted. Prediction of response to drugs using molecular biomarkers may be more accurate than clinical factors such as disease volume, 6,7 but their use in real-world clinical practice remains a challenge. There is an evident need for a simple clinicopathologic predictor for choosing ideal therapeutic strategies.…”

Section: Discussionmentioning

confidence: 99%

Clinical utility of intraductal carcinoma of the prostate in treatment selection for metastatic hormone‐sensitive prostate cancer

et al. 2022

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Background In recent years, the usefulness of androgen receptor axis‐targeted agents (ARATs) such as abiraterone, enzalutamide, and apalutamide for the upfront treatment of metastatic hormone‐sensitive prostate cancer (mHSPC) has been demonstrated. However, it remains unclear which patients would truly benefit from these treatments. Furthermore, intraductal carcinoma of the prostate (IDC‐P) is a known poor prognostic factor in patients with prostate cancer. We investigated the association between the presence of IDC‐P and response to therapy in patients with mHSPC. Methods This retrospective analysis included 318 patients with mHSPC who received treatment at Nagoya University and its 12 affiliated institutions between 2014 and 2021. Their biopsy specimens were evaluated for the presence of IDC‐P. The patients were classified according to their first‐line treatment into the ARAT (n = 100, receiving a combination of androgen‐deprivation therapy [ADT] and ARAT) or conventional therapy (n = 218, receiving ADT with or without standard antiandrogen agents) group. We compared the overall survival (OS) and second progression‐free survival (PFS2) between the ARAT and conventional groups according to the presence of IDC‐P to evaluate whether presence of IDC‐P predicts the response to each treatment. PFS2 was defined as the period from mHSPC diagnosis to disease progression on second‐line treatment or death. Propensity score matching with one‐to‐one nearest‐neighbor matching was used to minimize the potential effects of selection bias and confounding factors. The clinicopathological variables of the patients were well‐balanced after propensity score matching. Results Most patients in the ARAT (79%) and conventional therapy (71%) groups were ICD‐P positive. In the propensity score‐matched cohort, the OS and PFS2 of IDC‐P‐positive patients were significantly longer in the ARAT group than in the conventional group (OS: hazard ratio [HR], 0.36; p = 0.047; PFS2: HR, 0.30; p < 0.001). In contrast, no difference in OS and PFS2 was observed between the ARAT and conventional groups in IDC‐P‐negative patients (OS: HR, 1.09; p = 0.920; PFS2: HR, 0.40; p = 0.264). Conclusions The findings highlight a high prevalence of IDC‐P among patients with mHSPC and suggest that IDC‐P positivity may be a reliable indicator that ARAT should be implemented as first‐line treatment.

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“…Observational data analyses require special considerations when assessing the validity of biomarkers or effectiveness of drugs. To this end, we employed two complementary techniques: propensity analyses and crossover analyses, with interpretations resting on consistency of observations across different 5 cohorts and methods of evaluation, similar to prior real-world analyses in metastatic prostate cancer (16).…”

Section: Real-world Analysis Designmentioning

confidence: 99%

Real-world Validation of TMB and Microsatellite Instability as Predictive Biomarkers of Immune Checkpoint Inhibitor Effectiveness in Advanced Gastroesophageal Cancer

Graf

Fisher

Creeden

et al. 2022

Cancer Research Communications

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Patients with advanced gastroesophageal cancer (mEG) and tumor mutational burden ≥ 10 mut/mb (TMB≥10) have more favorable outcomes on immune checkpoint inhibitor (ICPI) monotherapy compared to chemotherapy in subgroup analyses of randomized controlled trials. We sought to evaluate the robustness of these associations in real-world settings where patients and practices are more diverse. 362 2L and 692 1L patients respectively received ICPI (n = 99, 33) or chemotherapy (n = 263, 659) across approximately 280 U.S. academic or community-based cancer clinics March 2014-July 2021. De-identified data was captured into a real-world clinico-genomic database (CGDB). All patients underwent Foundation Medicine testing. Time to next treatment (TTNT) and overall survival (OS) comparing ICPI vs. chemotherapy were adjusted for treatment assignment imbalances using propensity scores. 2L: TMB≥10 had more favorable TTNT (Median 24 vs. 4.1 months, HR: 0.19, 95%CI: 0.09–0.44, p=0.0001) and OS (median 43.1 vs. 6.2 months, HR: 0.24, 95%CI: 0.011–0.54, p=0.0005), TMB<10 did not (p>0.05). 1L: TMB≥10 had more favorable TTNT (not reached vs. median 4.1 months, HR: 0.13, 95%CI: 0.03–0.48, p=0.0024) and OS (not reached vs. median 17.1 months, HR: 0.30, 95%CI: 0.08–1.14, p=0.078), TMB<10 had less favorable TTNT (median 2.8 vs. 6.5 months, HR: 2.36, 95%CI: 1.25–4.45, p=0.008) and OS (median 4.5 vs. 13.1 months, HR: 1.82, 95%CI: 0.87–3.81, p=0.11). TMB ≥ 10 robustly identifies mEG patients with more favorable outcomes on 2L ICPI monotherapy vs. chemotherapy. 1L data are more limited, but effects are consistent with 2L.

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Predictive Genomic Biomarkers of Hormonal Therapy Versus Chemotherapy Benefit in Metastatic Castration-resistant Prostate Cancer

Cited by 18 publications

References 38 publications

A Pan-Cancer Analysis of Heat-Shock Protein 90 Beta1(HSP90B1) in Human Tumours

A Pan-Cancer Analysis of Heat-Shock Protein 90 Beta1(HSP90B1) in Human Tumours

Clinical utility of intraductal carcinoma of the prostate in treatment selection for metastatic hormone‐sensitive prostate cancer

Real-world Validation of TMB and Microsatellite Instability as Predictive Biomarkers of Immune Checkpoint Inhibitor Effectiveness in Advanced Gastroesophageal Cancer

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