What is ASPiRATION?
The ASPiRATION program was a pioneering partnership between government, industry and academia. The study was led by TOGA, in collaboration with Omico (Australian Genomic Cancer Medicine Centre) and the University of Sydney NHMRC Clinical Trials Centre (CTC). The program was supported by funding from the federal government’s Medical Research Future Fund (MRFF) and Roche.
The ASPiRATION program was the first of its kind in Australia to generate high-quality, real-world data about the impact and value of comprehensive genomic profiling (CGP; a type of next generation sequencing (NGS)) in delivering precision medicine and personalised healthcare. As well as generating important clinical data, ASPiRATION enabled access to testing for hundreds of genetic variants in a single test for 1000 newly diagnosed metastatic NSCLC patients. If an actionable genetic variant was identified, the patient was offered options to access targeted treatments, such as a clinical trial.
What is comprehensive genomic profiling and why was it important for people diagnosed with NSCLC?
At the time the ASPiRATION study was conducted, standard of care testing for people with newly diagnosed metastatic NSCLC was sequential testing for the EGFR, ALK and ROS1 fusion genes. These three genes are known as oncogenes that drive tumour growth. They can be effectively targeted with tyrosine kinase inhibitors (TKIs) enabling many people to live with metastatic NSCLC for many years, with minimal treatment side effects.
Other NSCLC oncogenes have been identified, and during 2020- 2023 many additional TKIs that targeted these other oncogenes were likely to be made available. However sequential testing, while available, took too much time and tissue, with tissue likely to be used up before the full panel of oncogenes could be tested.
CGP is an advanced type of next generation sequencing that enabled all possible oncogenes to be identified in a single test, as well as additional information about other tumour genes and mutations. Through additional clinical trials and access programs, targeted therapies for oncogenes HER2, NTRK fusion, MetEx14 skipping mutation, BRAFV600, ERBB2, RET fusion, NRG1 fusion and KRAS G12C (TOGA’s SHERLOCK trial) were made available.
Prof Nick Pavlakis describing the ASPiRATION study at the 2021 TOGA Annual Scientific Meeting 6 months after the study opened to recruitment.
What was the outcome of ASPiRATION?
ASPiRATION recruitment completed in June 2023, enrolling 1000 patients. The MoST substudies remained open for people diagnosed with particular oncogene-driven NSCLC, but in 2025 have also closed to recruitment.
ASPiRATION showed that it was possible to offer precision medicine determined from the genetic makeup of the tumour to metastatic NSCLC patients Australia-wide through remote referral, provision of preserved lung tissue from diagnostic biopsies and a central Molecular Tumour Board that determined available treatment options. ASPiRATION ensured equitable access to tests capable of identifying life-saving treatments for patients with rare forms of NSCLC. Several participants were able to access targeted therapies through clinical trials.
As well as a major advancement in research, the ASPiRATION study contributed to the feasibility of the MSAC item number for NGS in non-squamous NSCLC. Lung cancer is the first cancer to have genomic testing reimbursed by Medicare.
What’s next?
The resulting ASPiRATION study dataset will continue to be analysed to assess the prognostic and predictive impact of co-mutations and co-variants, potentially leading to new biomarkers and standards of care in NSCLC. The analysis for a survival benefit is underway with results submitted for a presentation at WCLC 2025.
Therapeutic options now exist for NSCLC expressing mutations in ALK, EGFR (incl EGFR Exon20ins), ROS1, RET, HER2, KRASG12C, or NTRK 1,2,3 genes, with the number that are reimbursed via PBS steadily growing. However, resistance to treatment is inevitable, and second-line treatments largely consist of chemotherapy and time of progression on TKIs in TOGA’s OSCILLATE and ALKTERNATE studies, as well as a growing body of evidence from other international studies has suggested that resistance to current generation TKIs is not exclusively due to escape variants of the primary oncogene, and that remaining on the TKI with adjunct therapies may be a reasonable option in some patients. In a research setting, CGP can now be offered on ‘liquid biopsy’ (blood samples) that are taken at various time points during treatment with the aim of monitoring continued response to the TKI.
How can mNSCLC patients access NGS and CGP now?
NGS for non-squamous NSCLC patients is now MBS-reimbursed. There are a minimum number of mutations that must be tested for reimbursement, but most panels will test many more. Medicare reimbursement does not include review by a molecular tumour board.
CaSP offers CGP centrally through Omico via referral for remote consent. With CaSP the expected turnaround time is 8-10 weeks. The results will be reviewed by a Molecular Tumour Board.
The CaSP referral form can be accessed via the following link: CaSP Referral Form
Further information about CaSP is available here via the Omico website, or contact casp@omico.org.au.
