NOMINATOR: Feasibility of genomic testing of rare cancers to match cancer to treatment.

Kee, Damien; Kondrashova, Olga; Ananda, Sumitra; Brown, Michael P.; Cohen, Paul A.; Dean, Andrew; Desai, Jayesh; Fellowes, Andrew; Fox, Stephen B.; Hadley, Alison; Lindsay, Dianne; Mileshkin, Linda; O’Byrne, Kenneth J.; Prall, Owen W.J.; Scott, Hamish S.; Thomas, David M.; Vines, Richard; Waddell, Nic; Papenfuss, Anthony T.; Scott, Clare L.

doi:10.1200/jco.2020.38.15_suppl.103

Cited by 4 publications

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“…The NOMINATOR study assessed the feasibility of genomic testing in rare cancers [70], also assessing actionability as per the OncoKB annotation [62]. This work optimistically reports 56% of rare tumours with at least one actionable finding.…”

Section: Genomic Alteration In Cupsmentioning

confidence: 99%

Redefining cancer of unknown primary: Is precision medicine really shifting the paradigm?

Thibault

Fernández

Labidi-Galy

et al. 2021

Cancer Treatment Reviews

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The concept of Cancer of Unknown Primary (CUP) has evolved with the advent of medical oncology. CUP can be difficult to diagnose and represents 2 to 5% of new cancers, therefore not exceptionally rare. Within CUPs can be identified a subset of favourable prognosis tumours, however the vast majority of CUP patients belongs to a poor prognosis group.CUP features significant oncological challenges, such as unravelling biological and transversal issues, and most importantly, improving patient's outcomes. In that regard, CUP patients' outcomes regrettably showed minimal improvement for decades and CUP remains a cancer group of very poor prognosis.The biology of CUP has two main hypotheses. One is that CUP is a subgroup of a given primary cancer, where the primary is present but cannot be seen due to its small size. The other, the "true" CUP hypothesis, states that CUP share features that make them a specific entity, whatever their tissue of origin. A true biological signature has not yet been described, but chromosomal instability is a hallmark of poor prognosis CUP group.Precision oncology, despite achieving identifying the putative origin of the CUP, so far failed to globally improve outcomes of patients. Targeting molecular pathways based on molecular analysis in CUP management is under investigation. Immunotherapy has not shown ground-breaking results, to date. Accrual is also a crucial issue in CUP trials.Herein we review CUP history, biological features and remaining questions in CUP biology, the two main approaches of molecular oncology in CUP management, in order to draw perspectives in the enormous challenge of improving CUP patient outcomes.

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Section: Genomic Alteration In Cupsmentioning

confidence: 99%

Redefining cancer of unknown primary: Is precision medicine really shifting the paradigm?

Thibault

Fernández

Labidi-Galy

et al. 2021

Cancer Treatment Reviews

View full text Add to dashboard Cite

show abstract

“…1,2 A recent study on rare and advanced tumors revealed that 51% of the tumors analyzed had ≥1 potentially actionable alteration. 3 Nowadays, multimarker tumor panel tests that examine DNA alterations in 200-300 genes are becoming highly used in clinical settings. 4,5 This is due to the growing conviction among clinicians regarding their clinical utility, the development of guidelines recommending their implementation, and the willingness of healthcare payers to provide coverage for the costs associated with these advanced tests.…”

Section: Introductionmentioning

confidence: 99%

Fusion Challenges in Solid Tumors: Shaping the Landscape of Cancer Care in Precision Medicine

Ahmed,

Torrado,

Chelariu

et al. 2024

JCO Precis Oncol

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Targeting actionable fusions has emerged as a promising approach to cancer treatment. Next-generation sequencing (NGS)–based techniques have unveiled the landscape of actionable fusions in cancer. However, these approaches remain insufficient to provide optimal treatment options for patients with cancer. This article provides a comprehensive overview of the actionability and clinical development of targeted agents aimed at driver fusions. It also highlights the challenges associated with fusion testing, including the evaluation of patients with cancer who could potentially benefit from testing and devising an effective strategy. The implementation of DNA NGS for all tumor types, combined with RNA sequencing, has the potential to maximize detection while considering cost effectiveness. Herein, we also present a fusion testing strategy aimed at improving outcomes in patients with cancer.

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Combination immunotherapy with ipilimumab and nivolumab in patients with advanced adrenocortical carcinoma: a subgroup analysis of CA209-538

et al. 2021

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Background : Adrenocortical carcinoma is a rare malignancy, with poor prognosis and limited treatment options for patients with advanced disease. Chemotherapy is the current standard first-line treatment, providing only a modest survival benefit. There is only limited treatment experience with immunotherapy using single-agent anti-PD-1/PD-L1 therapy. To date no clinical trials have been reported using combination immunotherapy with anti-CTLA-4 and anti-PD-1 blockade in this patient population. Methods : CA209-538 is a prospective multicentre clinical trial in patients with advanced rare cancers. Participants received the anti-PD-1 antibody nivolumab (3 mg/kg IV) and the anti-CTLA-4 antibody ipilimumab (1 mg/kg IV) every three weeks for four doses, followed by nivolumab (3 mg/kg IV) every two weeks and continued for up to 96 weeks, until disease progression or unacceptable toxicity. Response was assessed every 12 weeks by RECIST version 1.1. Primary endpoint was clinical benefit rate (complete response, partial response, stable disease at 12 weeks). Results : Six patients with adrenocortical carcinoma were enrolled and received treatment. Two patients (33%) have an ongoing partial response (10 and 25 months +) and two patients (33%) stable disease leading to a disease control rate of 66%. Both responders had tumors with a microsatellite instable phenotype. One patient rapidly progressed shortly after enrollment into the trial and did not undergo restaging. Immunotherapy-related toxicity was reported in all patients, with four patients (67%) experiencing grade 3/4 hepatitis leading to discontinuation of treatment. Conclusions : This is the first treatment experience using ipilimumab and nivolumab combination immunotherapy in patients with advanced adrenocortical carcinoma. Durable responses have been observed in a subset of patients suggesting that this treatment regimen should be further investigated in this patient population.

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NOMINATOR: Feasibility of genomic testing of rare cancers to match cancer to treatment.

Cited by 4 publications

References 0 publications

Redefining cancer of unknown primary: Is precision medicine really shifting the paradigm?

Redefining cancer of unknown primary: Is precision medicine really shifting the paradigm?

Fusion Challenges in Solid Tumors: Shaping the Landscape of Cancer Care in Precision Medicine

Combination immunotherapy with ipilimumab and nivolumab in patients with advanced adrenocortical carcinoma: a subgroup analysis of CA209-538

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