TY - JOUR
T1 - NOMINATOR: Feasibility of genomic testing of rare cancers to match cancer to treatment.
AU - Kee, Damien
AU - Kondrashova, Olga
AU - Ananda, Sumitra
AU - Brown, Michael Paul
AU - Cohen, Paul Andrew
AU - Dean, Andrew
AU - Desai, Jayesh
AU - Fellowes, Andrew
AU - Fox, Stephen B.
AU - Hadley, Alison
AU - Lindsay, Dianne
AU - Mileshkin, Linda R.
AU - O'Byrne, Kenneth John
AU - Prall, Owen W.J.
AU - Scott, Hamish
AU - Thomas, David Morgan
AU - Vines, Richard
AU - Waddell, Nic
AU - Papenfuss, Anthony
AU - Scott, Clare L.
PY - 2020/5
Y1 - 2020/5
N2 - 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
AB - 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
U2 - 10.1200/JCO.2020.38.15_suppl.103
DO - 10.1200/JCO.2020.38.15_suppl.103
M3 - Abstract/Meeting Abstract
SN - 0732-183X
VL - 38
SP - 103
JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
IS - 15_suppl
ER -
