What is precision medicine in lung cancer?
Precision medicine matches treatments to a patient’s specific genetic mutations — such as ALK or EGFR in NSCLC — to improve outcomes and reduce side effects.
The Birth of Targeted Therapy in Lung Cancer
ALK: From Laboratory Curiosity to Lifesaving Treatment
The ALK gene was first discovered in the 1990s in another type of cancer. Its role in lung cancer wasn’t understood until 2007, when researchers found a gene fusion that acted as an “on switch” for cancer growth in a small subset of patients with non-small cell lung cancer (NSCLC).
This breakthrough led to crizotinib, the first ALK-targeted therapy, which delivered dramatic improvements for patients with ALK-positive lung cancer in an international Phase III clinical trial led by TOGA’s Professor Ben Solomon.
"When we first saw responses to crizotinib in ALK-positive lung cancer, it was a watershed moment— it became very clear that what was needed was a tailored approach to treatment rather than a one-size-fits-all approach. Precision medicine has completely redefined and expanded the horizons of what’s possible for patients. Today, we can match therapies to the biology of each individual’s tumour and offer access to cutting-edge clinical trials that weren’t imaginable 15 years ago. It’s been a privilege to witness—and possibly also contribute - to this transformation.”
EGFR: A Reverse Discovery That Changed Everything
The story of EGFR mutation lung cancer unfolded differently. Before scientists knew EGFR mutations existed, tyrosine kinase inhibitors (TKIs) like gefitinib were already in trials.
In the landmark IPASS trial, gefitinib delivered exceptional results — particularly among non-smoking Asian women with a type of lung cancer called adenocarcinoma. Only later did researchers discover these patients carried EGFR mutations that made their cancers uniquely sensitive to the drug.
This became the first success in targeted therapy lung cancer driven by a genetic biomarker — and it changed the treatment landscape forever.
Precision Medicine Becomes Standard Care
Today, testing for ALK, EGFR, and other oncogenes on biopsy tissue is routine in NSCLC through an MBS-reimbursed small gene next generation sequencing (NGS) panel allowing doctors to match patients with the most effective treatments. In 2025, TOGA and RCPA launched the Best Practice Recommendations for Molecular testing in Lung Cancer.
There are a variety of targeted therapies for NSCLC harbouring particular mutations available on the PBS (see Figure below), with other agents in clinical trials.
These advances were possible thanks to collaboration between researchers, pharmaceutical companies, clinical trial networks, and patients — the foundation for the current era of precision medicine lung cancer.
TOGA’s Role in the Next Era of Precision Medicine
The Thoracic Oncology Group of Australasia (TOGA) drives innovation by:
- Expanding lung cancer genomic testing across Australia for both tissue and liquid biopsy
- Leading multicentre clinical trials for targeted therapy lung cancer
- Investigating drug resistance in oncogene-driven cancers
- Delivering high-quality education on emerging changes in practice
- Developing and communicating clinical practice recommendations
TOGA Clinical Trials Shaping the Future
ASPiRATION: Comprehensive Genomic Profiling for All Australians with NSCLC
- Provided a single test to detect all known oncogenes in metastatic lung cancer and successfully changed tissue biopsy practice to ensure sufficient tissue was collected for this testing.
- Linked patients with clinical trials when targeted therapy was not yet PBS-reimbursed.
- Researched co-mutations contributing to resistance in EGFR mutation lung cancer and other oncogene-driven cancers.
ALKTERNATE: Understanding Resistance in ALK-Positive NSCLC
- Tested alternating cycles between 2nd and 3rd generation TKIs in a pre-treated population to delay resistance in ALK-positive lung cancer.
- Found no progression-free survival benefit, but revealed that with 3rd generation TKIs, resistance is rarely due to a single mutation.
- Data contributes to a global understanding of precision medicine in lung cancer.
OSCILLATE: Alternating TKI Therapy in Pre-Treated EGFR+ NSCLC
- Alternated 2nd- and 3rd-generation TKIs in pre-treated EGFR+ NSCLC patients.
- Median PFS was 9.4 months, similar to continuous osimertinib (10.1 months).
- Distinct clonal dynamics observed in ctDNA: both EGFRm and T790M clones were suppressed, and C797S-mediated resistance was delayed in some patients.
- Resistance was heterogeneous, underscoring the need for repeat tumour or liquid biopsies to guide future treatment strategies.
ASPiRATION2L (Opening 2026): Real-Time Resistance Tracking
- Will study rational therapy combinations after resistance to first-line TKIs emerges.
- Uses serial liquid biopsy for real-time genomic profiling.
- Aims to offer immediate new options after primary resistance develops in targeted therapy lung cancer.
SHERLOCK (in follow up)
- Examined whether a KRAS G12C inhibitor in combination with chemotherapy and bevacizumab as first line treatment for KRAS G12C+ metastatic NSCLC improves the response to treatment
OCEANIC (currently recruiting)
- Building on emerging evidence that ctDNA clearance predicts better response to treatment, OCEANIC allocates patients with Stage IIA-IIIA with ctDNA remaining post-surgery and high-risk co-mutation positive to chemotherapy plus osimertinib.
