Dataset Information

Radiopharmaceuticals for Relapsed or Refractory Ovarian Cancers.

ABSTRACT: Targeted radiopharmaceuticals for therapeutic use deliver radionuclides directly to tumor anywhere in the body, and therefore, have renewed interest for clinical development in women with disseminated chemorefractory ovarian cancers. About two in every five women with advanced stage ovarian cancer outlive their disease after the first treatment phase, with the rest rendered incurable due to the chemorefractory nature of their disease. The National Cancer Institute (NCI) Cancer Therapy Evaluation Program conducted 67 phase I or phase Ib trials among women with relapsed or refractory ovarian cancer between 1989 and 2017 in an effort to uncover tolerable and effective drug combinations intended to increase survival rates. None of these early clinical development phase trials involved radiopharmaceuticals. Here, the NCI provides its perspective on targeted radiopharmaceutical conjugates alone or in combination with its experimental therapeutics portfolio for women with relapsed or refractory ovarian cancer. An infrastructure build for Federal radiopharmaceutical medical monitoring and adverse event reporting has begun.

SUBMITTER: Kunos CA

PROVIDER: S-EPMC6448015 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Radiopharmaceuticals for Relapsed or Refractory Ovarian Cancers.

Kunos Charles A CA Capala Jacek J Finnigan Shanda S Smith Gary L GL Ivy Susan Percy SP

Frontiers in oncology 20190326

Targeted radiopharmaceuticals for therapeutic use deliver radionuclides directly to tumor anywhere in the body, and therefore, have renewed interest for clinical development in women with disseminated chemorefractory ovarian cancers. About two in every five women with advanced stage ovarian cancer outlive their disease after the first treatment phase, with the rest rendered incurable due to the chemorefractory nature of their disease. The National Cancer Institute (NCI) Cancer Therapy Evaluation ...[more]

PMID: 30984615

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Project description:BackgroundNew clinical genomic assays for lymphoid cancers allow for improved disease stratification and prognostication. At present, clinical implementation has been appropriately limited, owing to a paucity of evidence to support clinical and cost effectiveness. Understanding patients' values for precision oncology under conditions of uncertainty can be used to inform priority-setting decisions.ObjectivesOur objective was to ascertain patients' qualitative preferences and attitudes for prognostic-based genomic testing.MethodsIndividuals who were diagnosed with lymphoid cancer between 2000 and 2018 in British Columbia, Canada, were recruited to participate in one of three focus groups. A maximum variation sampling technique was used to capture a diversity of perspectives. A patient partner was involved in the development of the focus group topic guide and presentation materials. All sessions were audio recorded and analyzed using NVivo qualitative analysis software, version 12.ResultsIn total, 26 participants took part in focus groups held between November 2018 and February 2019. Results illustrate qualitative preference heterogeneity for situations under which individuals would be willing to undergo genomic testing for relapsed lymphoid cancers. Preferences were highly contextualized within personal experiences with disease and treatment protocols. Hypothetical willingness to pay for testing was contingent on invasiveness, the potential for treatment de-escalation, and personal health benefit.ConclusionsPatients are supportive and accepting of evidentiary uncertainty up until the point at which they are required to trade-off the potential for improved quality and length of life. Demand for precision medicine is contingent on expectations for benefit alongside an acknowledgment of the opportunity cost required for implementation. The clinical implementation of precision medicine will be required to address evidentiary uncertainty surrounding personal benefit while ensuring equitable access to emerging innovations.

Project description:Purpose of reviewThere have been significant advances in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) over the past two decades. However, the intention of treatment remains control of the disease and delay of progression rather than a cure which remains largely elusive. Considering that CLL is mostly seen in older patients, there are multiple factors that play a role in the selection of CLL beyond the frontline treatment. Here, we review the concept of relapsed CLL, factors that predispose to relapse, and therapeutic options available to this patient population. We also review investigational therapies and provide a framework for selection of therapies in this setting.Recent findingsPlease check if the affiliations are presented correctly.Targeted therapies with continuous BTK inhibitors (BTKi) or fixed duration venetoclax plus anti-CD20 monoclonal antibody therapy have established superiority over chemoimmunotherapy in relapsed CLL and have become the preferred standard of care treatment. The second-generation more selective BTK inhibitors (acalabrutinib and zanubrutinib) have shown improved safety profile compared to ibrutinib. However, resistance to the covalent BTK inhibitors may emerge and is commonly associated with mutations in BTK or other downstream enzymes. The novel non-covalent BTK inhibitors such as pirtobrutinib (Loxo-305) and nemtabrutinib (ARQ 531) are showing promising activities for relapsed CLL refractory to prior covalent BTKi. Other novel therapies such as chimeric antigen receptor (CAR) T cell therapy have also shown significant activities for relapsed and refractory CLL. Measurable residual disease (MRD) assessment has a growing importance in venetoclax-based limited-duration therapy and there is mounting evidence that MRD negativity improves outcomes. However, it remains to be seen if this will become an established clinically significant endpoint. Further, the optimal sequence of various treatment options remains to be determined. Patients with relapsed CLL now have more options for the treatment of the disease. The choice of therapy is best individualized especially in the absence of direct comparisons of targeted therapies, and the coming years will bring more data on the best sequence of use of the therapeutic agents.

Dataset Information

Radiopharmaceuticals for Relapsed or Refractory Ovarian Cancers.

Publications

Radiopharmaceuticals for Relapsed or Refractory Ovarian Cancers.

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