Clinical utility of FoundationOne tissue molecular profiling in men with metastatic prostate cancer

Zhu, Jason; Tucker, Matthew D.; Marin, Daniele; Gupta, Rajan T.; Healy, Patrick; Humeniuk, Michael S.; Jarvis, Casey A.; Zhang, Tian; McNamara, Megan Ann; George, Daniel J.; Wu, Yuan; Lisi, Stacey; Armstrong, Andrew J.

doi:10.1016/j.urolonc.2019.06.015

Cited by 20 publications

(13 citation statements)

References 47 publications

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“…Approximately 10% of the cases were performed using FoundationOne (Foundation Medicine, Cambridge, Massachusetts). StrataNGS interrogated approximately 100 to 400 genes and FoundationOne interrogated approximately 300 to 400 genes [ 23 , 24 ].…”

Section: Methodsmentioning

confidence: 99%

Fourteen-Day Gemcitabine-Docetaxel Chemotherapy Is Effective and Safer Compared to 21-Day Regimen in Patients with Advanced Soft Tissue and Bone Sarcoma

Pan

Trieu

Sidhu

et al. 2021

Cancers

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Gemcitabine-docetaxel (G-D) combination is an effective chemotherapy for patients with advanced soft tissue and bone sarcoma, first developed with G administered on days 1 and 8, and D on day 8 every 21 days and later modified to be administered every 14 days in 2012. The 14-day regimen has become increasingly adopted. However, its efficacy and toxicities have not been compared. We identified 161 patients with metastatic or locally advanced soft tissue and bone sarcoma treated with either a 14-day or 21-day regimen within Northern California Kaiser Permanente from 1 January 2017 to 30 July 2020 and compared the outcomes and toxicity profiles of patients treated with the either regimen. Seventy-nine (49%) and 82 (51%) patients received the 14-day and the 21-day regimen, respectively, with similar response rate (22.8% and 15.8%, p = 0.26), median progression-free survival (PFS, 4.0 and 3.2 months, p = 0.15), and median overall survival (OS, 12.6 and 14.7 months, p = 0.55). Subset analysis of the untreated patients (approximately 60% of the entire cohort) as well as the patients with leiomyosarcoma only (approximately 50% of the entire cohort) showed that OS was not significantly different between the two regimens. Febrile neutropenia requiring hospitalization occurred in 10 and one patients (p = 0.006) and intolerance leading to discontinuation of chemotherapy occurred in 12 and two patients (p = 0.006) treated with the 21-day and the 14-day regimens, respectively. CDKN2A deletion/mutation or CDK4 amplification was associated with worse median OS (p = 0.06), while a RB1 deletion/mutation was associated with better median PFS (p = 0.05), and these two genomic alterations were mutually exclusive. Our data demonstrate that, compared to the traditional 21-day G-D regimen, the 14-day G-D regimen is equally effective but safer. In addition, CDKN2A and RB1 pathways play significant role on the outcomes of the patients.

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Section: Methodsmentioning

confidence: 99%

Fourteen-Day Gemcitabine-Docetaxel Chemotherapy Is Effective and Safer Compared to 21-Day Regimen in Patients with Advanced Soft Tissue and Bone Sarcoma

Pan

Trieu

Sidhu

et al. 2021

Cancers

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“…We present here a broad analysis of our NGS testing characteristics and the molecular landscape of detected alterations. Other teams within our institution have also made use of our centralized tumor registry for clinical research projects, [33][34][35] and our database has enabled our participation in the American Association of Cancer Research Genomics Evidence Neoplasia Information Exchange data sharing initiative. 36 Although we consider our MTB program successful based on our ability to achieve the goals discussed above, only 17% (36 of 215) of patients included in our MTB analysis received a matched targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

Implementation of a Molecular Tumor Registry to Support the Adoption of Precision Oncology Within an Academic Medical Center: The Duke University Experience

Green

Bell

Hubbard

et al. 2021

JCO Precision Oncology

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PURPOSE Comprehensive genomic profiling to inform targeted therapy selection is a central part of oncology care. However, the volume and complexity of alterations uncovered through genomic profiling make it difficult for oncologists to choose the most appropriate therapy for their patients. Here, we present a solution to this problem, The Molecular Registry of Tumors (MRT) and our Molecular Tumor Board (MTB). PATIENTS AND METHODS MRT is an internally developed system that aggregates and normalizes genomic profiling results from multiple sources. MRT serves as the foundation for our MTB, a team that reviews genomic results for all Duke University Health System cancer patients, provides notifications for targeted therapies, matches patients to biomarker-driven trials, and monitors the molecular landscape of tumors at our institution. RESULTS Among 215 patients reviewed by our MTB over a 6-month period, we identified 176 alterations associated with therapeutic sensitivity, 15 resistance alterations, and 51 alterations with potential germline implications. Of reviewed patients, 17% were subsequently treated with a targeted therapy. For 12 molecular therapies approved during the course of this work, we identified between two and 71 patients who could qualify for treatment based on retrospective MRT data. An analysis of 14 biomarker-driven clinical trials found that MRT successfully identified 42% of patients who ultimately enrolled. Finally, an analysis of 4,130 comprehensive genomic profiles from 3,771 patients revealed that the frequency of clinically significant therapeutic alterations varied from approximately 20% to 70% depending on the tumor type and sequencing test used. CONCLUSION With robust informatics tools, such as MRT, and the right MTB structure, a precision cancer medicine program can be developed, which provides great benefit to providers and patients with cancer.

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“…that approximately 60-70% of primary and metastatic samples from patients with prostate cancer have successful test results [9,17,23,24]. These findings highlight that the optimisation of diagnostic tissue collection and processing to provide an adequate quantity of highquality tumour samples is crucial for the testing process as primary specimens are currently the preferred source of material for HRR analysis [11,18,25,51].…”

Section: Gonzalez Et Almentioning

confidence: 96%

“…Real-world data on the testing success of prostate tumour samples are limited as clinical next-generation sequencing (NGS) has only recently been implemented for this tumour type outside of the context of clinical [9,17,23,24]. Consequently, there is an urgent need to significantly improve testing approaches.…”

Section: Opportunities and Challenges In Mcrpcmentioning

confidence: 99%

Practical considerations for optimising homologous recombination repair mutation testing in patients with metastatic prostate cancer

González

Mateo

Stenzinger

et al. 2021

The Journal of Pathology CR

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Analysis of the genomic landscape of prostate cancer has identified different molecular subgroups with relevance for novel or existing targeted therapies. The recent approvals of the poly(ADP-ribose) polymerase (PARP) inhibitors olaparib and rucaparib in the metastatic castration-resistant prostate cancer (mCRPC) setting signal the need to embed molecular diagnostics in the clinical pathway of patients with mCRPC to identify those who can benefit from targeted therapies. Best practice guidelines in overall biospecimen collection and processing for molecular analysis are widely available for several tumour types. However, there is no standard protocol for molecular diagnostic testing in prostate cancer. Here, we provide a series of recommendations on specimen handling, sample pre-analytics, laboratory workflow, and testing pathways to maximise the success rates for clinical genomic analysis in prostate cancer. Early involvement of a multidisciplinary team of pathologists, urologists, oncologists, radiologists, nurses, molecular scientists, and laboratory staff is key to enable optimal workflow for specimen selection and preservation at the time of diagnosis so that samples are available for molecular analysis when required. Given the improved outcome of patients with mCRPC and homologous recombination repair gene alterations who have been treated with PARP inhibitors, there is an urgent need to incorporate high-quality genomic testing in the routine clinical pathway of these patients.

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Clinical utility of FoundationOne tissue molecular profiling in men with metastatic prostate cancer

Cited by 20 publications

References 47 publications

Fourteen-Day Gemcitabine-Docetaxel Chemotherapy Is Effective and Safer Compared to 21-Day Regimen in Patients with Advanced Soft Tissue and Bone Sarcoma

Fourteen-Day Gemcitabine-Docetaxel Chemotherapy Is Effective and Safer Compared to 21-Day Regimen in Patients with Advanced Soft Tissue and Bone Sarcoma

Implementation of a Molecular Tumor Registry to Support the Adoption of Precision Oncology Within an Academic Medical Center: The Duke University Experience

Practical considerations for optimising homologous recombination repair mutation testing in patients with metastatic prostate cancer

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