Rare cancers (RCs) are difficult to research and consequently often lack evidence-based treatments. Identifying underlying genomic biomarkers may allow more rational selection of treatments or clinical trials. We report treatment and survival in RC patients (pts) following next-generation sequencing (NGS) in the NOMINATOR study (ACTRN12616001000493).
Pts with rare histology, poor-prognosis solid-tumours, and limited treatment options underwent NGS (PMCC panel; 391 genes) of paired tumour:blood DNA. Virtual molecular tumour board review of clinical history, pathology and genomic results for actionability (OncoKB) provided treatment recommendations. Pt were followed for up to 2 years for impact on treatment and outcomes.
121 pts were prospectively enrolled between July 2017 to Nov 2019 and 100 tumours successfully sequenced. 56 (56%) had potentially actionable results: 27 matched to a clinically validated drug; and 29 a biologically plausible treatment. As of August 2020, of 94 pt with advanced stage disease (and excluding hormonal therapies), 13 started one or more lines of genomically-matched therapy; 57 an unmatched therapy; and 24 received no further treatment. Pts were more likely to access a matched therapy for approved indications (5/5) or with stronger evidence (OncoKB 2, 5/12). Drug access was provided by government (PBS) (4), self-funded (3), pharma (3) or clinical trial (4). Median OS (mOS) from consent for pts receiving matched, unmatched, and no treatment was 20.9 (n=13), 16.5 (57) and 20.1 (24) months, respectively. Corresponding mOS from advanced disease was 27.3, 31.0 and 33.8 months. 8 pts died prior to or within 28 days of NGS result availability.
NGS in RCs was feasible and identified potentially actionable results in half of cases. OS was similar across treatment groups explored, although heterogeneity in RC type and prior treatments limit analysis. Earlier testing and improved drug/trial access, including combination therapies, may improve likelihood of benefit from NGS.