Cancer Molecular Screening and Therapeutics (MoST): a framework for multiple, parallel signal‐seeking studies of targeted therapies for rare and neglected cancers

Thavaneswaran, Subotheni; Sebastian, Lucille; Ballinger, Mandy L.; Best, Megan; Hess, Dominique; Lee, Chee Khoon; Sjoquist, Katrin Marie; Hague, Wendy; Butow, Phyllis; Simes, R. J.; Thomas, David M.

doi:10.5694/mja18.00227

Cited by 41 publications

(40 citation statements)

References 17 publications

(31 reference statements)

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“…Participants were recruited to the Molecular Screening and Therapeutics (MoST) cancer genomic study, which is recruiting adult patients with pathologically confirmed advanced or metastatic solid cancers (of any histological type) who have exhausted therapeutic options. 6 Participants undergo MP and, if an actionable variant is found, are enrolled in a related therapeutic trial if available. Participants can elect to receive actionable, non-actionable and/or germline results at the time of consent, and to allow germline results to be returned to family members in the event of the participant's death.…”

Section: Methodsmentioning

confidence: 99%

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Advanced cancer patient preferences for receiving molecular profiling results

et al. 2020

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Objective: This study aimed to discern preferences for receiving somatic molecular profiling (MP) results in cancer patients who have given consent to undergo testing. Methods: We conducted a mixed-methods study to explore patients' views on which MP results they would like to receive and why. Advanced cancer patients (n = 1299) completed questionnaires after giving consent to participate in a parent genomics study and undergoing MP. A subset of patients (n = 20) participated in qualitative interviews. Results: Almost all (96%) participants were interested in receiving results which would direct cancer treatment (ie, were actionable). A smaller majority wanted to access results which were not actionable (64%) or were variants of unknown significance (60%). Most (86%) were interested in finding out about germline findings, though not as a priority. Themes identified in interview data were: (a) Cancer is the focus; (b) Trust in clinicians; and (c) Respect for a right not to know. Conclusions: The majority of advanced cancer patients undergoing MP prioritised results which would lead to treatment options. They trusted their oncologists to help them navigate the results return process. While there was interest in knowing about other results, this was a lesser priority. Nevertheless, given high levels of interest in receiving all results, ethical aspects of not providing uninformative results requires further research, including a consideration of patient rationales for desiring this information and what health professionals can and should do to support patients in the absence of meaningful information being available.

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Section: Methodsmentioning

confidence: 99%

“…This mixed-methods study aimed to examine the preferences for receiving results of advanced cancer patients who were actually undergoing MP (under a research protocol) in order to access novel therapies. 6…”

Section: Introductionmentioning

confidence: 99%

Advanced cancer patient preferences for receiving molecular profiling results

et al. 2020

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“…The Molecular Screening and Therapeutics (MoST) Program is a study underway at the Garvan Institute of Medical Research in Sydney, Australia [12]. It is recruiting 1,000 adult participants with pathologically confirmed advanced or metastatic solid cancer, with a particular focus on rare cancer.…”

Section: Methodsmentioning

confidence: 99%

“…Details of inclusion and exclusion criteria for MoST are reported in full in the MoST protocol paper [12]. In summary, the target population comprises adult participants with pathologically confirmed advanced or metastatic solid cancers of any histological type, either during or after their last line of effective therapy; participants have Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2; and have sufficient accessible tissue for molecular profiling.…”

Section: Methodsmentioning

confidence: 99%

Patient perspectives on molecular tumor profiling: “Why wouldn’t you?”

et al. 2019

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Aim This study explored the attitudes of patients with advanced cancer towards MTP and return of results, prior to undergoing genomic testing within a research program. Methods Participants were recruited as part of the longitudinal PiGeOn (Psychosocial Issues in Genomics in Oncology) study involving patients with advanced/metastatic solid cancer who had exhausted therapeutic options and who were offered MTP in order to identify cognate therapies. Twenty patients, selected by purposive sampling, were interviewed around the time they gave consent to MTP. Interviews were audio recorded, transcribed and analysed using thematic analysis. Themes identified in the transcripts were cross-validated via qualitative responses to the PiGeOn study survey ( n = 569; 63%). Results All interviewed participants gave consent to MTP without reservation. Three themes were identified and further supported via the survey responses: (1) Obvious agreement to participate , primarily because of desire for new treatments and altruism. (2) The black box – while participant knowledge of genomics was generally poor, faith in their oncologists and the scientific process encouraged them to proceed with testing; and (3) Survival is the priority – receiving treatment to prolong life was the priority for all participants, and other issues such as identification of a germline variant were generally seen as ancillary. Conclusion Having advanced cancer seemed to abrogate any potential concerns about MTP. Participants valued the research for varied reasons, but this was secondary to their priority to survive. While no negative attitudes toward MTP emerged, limitations in understanding of genomics were evident. Electronic supplementary material The online version of this article (10.1186/s12885-019-5920-x) contains supplementary material, which is available to authorized users.

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“…With tremendous progress in cancer biology and molecular diagnostics, cancer treatment is increasingly reliant on tumour molecular profiling to inform rational treatment decisions. To date, large precision oncology programs have harnessed the advances in genomic technology to inform design of a plethora of molecular matched trials [1][2][3][4][5][6][7][8]. Molecular testing, typically based on DNA and RNA sequencing, immunohistochemistry and in situ hybridization, is used to identify biomarkers that may predict response of cancers to particular targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

Criteria-based curation of a therapy-focused compendium to support treatment recommendations in precision oncology

Lin

Thavaneswaran

Grady

et al. 2020

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BACKGROUNDWhile several key resources exist that interpret therapeutic significance of genomic alterations in cancer, many regional real-world issues limit access to drugs. There is a need for a pragmatic, evidence-based, context-adapted tool to guide clinical management based on molecular biomarkers.METHODSA compendium of approved and experimental therapies with associated biomarkers was built following a survey of drug regulatory databases, existing knowledge bases, and published literature. Each biomarker-disease-therapy triplet was then categorized using a tiering system reflective of key therapeutic considerations: approved and reimbursed standard-of-care therapies with respect to a jurisdiction (Tier 1), evidence of efficacy or approval in another jurisdiction (Tier 2), evidence of antitumour activity (Tier 3), and plausible biological rationale (Tier 4). Two resistance categories were defined: lack of efficacy (Tier R1), and lack of antitumor activity (Tier R2).RESULTSFollowing comprehensive literature review and appraisal, we developed a curated knowledge base focused on drugs relevant and accessible in the Australian healthcare system (TOPOGRAPH: Therapy Oriented Precision Oncology Guidelines for Recommending Anticancer Pharmaceuticals). As of November 2020, TOPOGRAPH comprised 2810 biomarker-disease-therapy triplets in 989 expert-appraised entries, including 373 therapies, 199 predictive biomarkers, and 106 cancer types. In the 345 biomarker-linked therapies catalogued, 84 (24%) and 65 (19%) therapies in contexts of different cancer types have Tier 1 and 2 designations respectively, while 271 (79%) therapies were supported by preclinical studies, early clinical trials, retrospective studies, or case series (Tiers 3 and 4). A total of 119 of 373 (33%) therapies associated with biomarkers of resistance were also catalogued. A clinical algorithm was also developed to support therapeutic decision-making using predictive biomarkers. This resource is accessible online at https://topograph.info/.CONCLUSIONTOPOGRAPH is intended to support oncologists with context-appropriate clinical decision-making– optimising selection and accessibility of the most appropriate targeted therapy for any given genomic biomarker. Our approach can be readily adapted to build jurisdiction-specific resources to standardise decision-making in precision oncology.

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Cancer Molecular Screening and Therapeutics (MoST): a framework for multiple, parallel signal‐seeking studies of targeted therapies for rare and neglected cancers

Cited by 41 publications

References 17 publications

Advanced cancer patient preferences for receiving molecular profiling results

Advanced cancer patient preferences for receiving molecular profiling results

Patient perspectives on molecular tumor profiling: “Why wouldn’t you?”

Criteria-based curation of a therapy-focused compendium to support treatment recommendations in precision oncology

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