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

Damien Kee, Olga Kondrashova, Sumitra Ananda, Michael Paul Brown, Paul Andrew Cohen, Andrew Dean, Jayesh Desai, Andrew Fellowes, Stephen B. Fox, Alison Hadley, Dianne Lindsay, Linda R. Mileshkin, Kenneth John O'Byrne, Owen W.J. Prall, Hamish Scott, David Morgan Thomas, Richard Vines, Nic Waddell, Anthony Papenfuss, Clare L. Scott

Research output: Contribution to journalAbstract/Meeting Abstract

Abstract

Background: Rare cancers (RCs) often lack proven treatments and consequently have poorer outcomes. Identification of molecular biomarkers can facilitate treatment selection and trials access for RC patients (pts) where histology-based trials are not feasible. We assessed the potential for next-generation sequencing (NGS) to impact RC care. Methods: Pts with a rare histology, poor-prognosis solid-tumor and no standard of care therapy underwent NGS genomic profiling of paired FFPE tumor and blood (PMCC comprehensive cancer panel; 391 genes). A virtual molecular tumour board (MTB) reviewed curated results regarding diagnosis, actionability (OncoKB) and treatment recommendations. Results: Between July 2017 and Nov 2019, 121 pt were prospectively enrolled across 4 Australian sites. 109 (91%) pts had a tumour with an incidence of 10%) were: TP53 (45%), CDKN2A/B, RB1, PTEN and NF1. 51 (51%) had at least one potentially actionable finding, with 27 matched to a clinically validated drug (OncoKB level 3 or better) [Table]. In 6 cases NGS resulted in a revised diagnosis (includes 4 with FDA approved therapy). Actionable germline mutations were detected in 3 individuals of which 2 were previously known. The majority of pts remain in follow-up, however, 8 died prior to or within 28 days of NGS result availability. Drug access remains a limitation with only 12 receiving therapy based on NGS/MTB guidance. Clinical trial information: ACTRN12616001000493. Conclusions: NGS in RCs is feasible with potential impact in half of cases. Earlier testing and improved off-label/trial drug access is necessary to increase the likelihood that RC patients may benefit from molecularly guided therapy. OncoKB Level(Best result per tumour)N(100)Genetic biomarker/DiagnosisNo findings5Currently not actionable44Includes: TP53, RB1, APC, ARID1A, KMT2D, FAT1, NF2, ATM, ATRX, PBRM1, SMAD44 or clinical trial biomarker24CDKN2A/B, EGFR amp, MAPK1, NF1, PTEN, RAF1-fusion, SMARCA4/B1, TMB high, XPO138AKT, FGFR2-fusion, HRAS, PIK3CA, PTCH1212ERBB2 amp, BRAF, gBRCA1/2, IDH2, TSC1/217BRAF, MSH2/6, Melanoma# (4)#Revised diagnosis6RHM > ASTB, DLMGNT > DNT, MEL (4)Germline13ATM, BRCA1/2, CYP2D6, ERCC2, FANCA, FH, MUTYH, NF1, SDHC
Original languageEnglish
Pages (from-to)103
Number of pages1
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume38
Issue number15_suppl
DOIs
Publication statusPublished - May 2020

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