What Australia’s Largest ALK+ Study Tells Us About Survival

September 9, 2026

Treatment Patterns, Prognostic Factors and Survival for ALK-Positive Advanced NSCLC in Australia: Results From the Australasian Thoracic Cancers Longitudinal Cohort Study and Biobank (AURORA)

Grace Chazan, Marliese Alexander, Fanny Franchini, Maarten IJzerman, Roma Shah, Ani John, Tim Spelman, Malinda Itchins, Nick Pavlakis, Adnan Nagrial, Lydia Warburton, Samantha Bowyer, Steven Kao, Sagun Parakh, Benjamin J Solomon

Abstract

Introduction: Advanced lung cancer has historically been associated with poor survival. However, with the advent of targeted therapies, outcomes are improving. Among patients with ALK-rearranged advanced NSCLC (ALK+ aNSCLC), real-world data on treatment patterns, prognostic factors, and survival in the era of contemporary therapy remain limited.

Methods: Researchers conducted a retrospective observational cohort study using deidentified patient, disease, and outcomes data from the AUstralasian thoRacic cancers lOngitudinal cohoRt study and biobAnk (AURORA; ACTRN12625000038493). Eligible patients were diagnosed with ALK+ aNSCLC between 2006 and 2025.

Results: Of the 4,776 patients with thoracic malignancies enrolled across eight sites (as of April 2025), 218 met the inclusion criteria — the largest reported Australian cohort of ALK+ aNSCLC. All patients were treated in academic centres. The median age was 55 years; 54% were female, 66% were never-smokers, and 41% had participated in a clinical trial. The median overall survival was 90.8 months (95% CI: 69.8–not reached). Nearly all patients (99%) received an ALK inhibitor; 83% in the first-line setting. Treatment sequences evolved over time. Most (68%) received at least two lines of therapy; 21% received four or more lines. Smoking status, age, and Eastern Cooperative Oncology Group Performance Status were prognostically associated with survival.

Conclusion: This study highlights the remarkable survival achievable in the real-world setting for some patients with ALK+ aNSCLC, compared with historical cohorts. Several clinical factors associated with survival were identified. Larger studies are needed to investigate how treatment sequences may be optimized to further improve survival outcomes.

Interpretation of Results by Duncan Preece

The seminal study for ALK patients was the ALEX trial, carried out between 2014 and 2017 in the clinical setting, though adjusted statistically until 2025. This showed a median overall PFS (Progression-Free Survival) of 35 months, and median OS (Overall Survival) of 81 months on Alectinib. This was compared to Crizotinib, a first-generation TKI. (The median means the same number of patients before and after a data point. This is not the same as average, which pools all the patients together and divides by the number of patients.) The median is the standard reference in medicine.

The AURORA study brought in a different viewpoint: it took in 218 ALK patients, the largest ALK study ever done in Australia. However, these patients were treated over a 20-year period and took in patients right from the start of the discovery of the ALK fusion in 2007 until 2026. Furthermore, the first patients were treated by chemotherapy and radiation, the subsequent ones with Crizotinib, then some on Ceritinib, though the majority on Alectinib and then Lorlatinib, with a sprinkling of patients on Brigatinib. All patients were treated in academic centres, a well-known, though undefinable, clinical advantage.

AURORA shows a median OS of 90 months, about one year more than the ALEX study. However, this mixes in all these treatments and gives one overall result. As always, details count. A breakdown of these patients, it is fair to assume, would show huge differences between those treated 20 years ago on primitive treatments, and would not give the same result as if we took patients only diagnosed, say, from January 2020 onwards. While we wait for a finer breakdown of these patients, we can safely say that cumulative lines of treatment will show a remarkable outcome for those with access to several lines of treatment. Other studies that are ongoing would place this bar well over 10 years, and, in all likelihood, quite a bit more again.

There are also those patients who do not do well, and either burn through their TKIs very rapidly, or don’t even respond at all. We know part of the reason, though not all, which is why the first two years post-diagnosis, in particular, are so important.

As many of you are well aware, access to Lorlatinib in the second line of therapy is hugely problematic in Canada, and other new TKIs may well be subject to the same accessibility and equity of access issues in the months and years to come. If you’re interested in participating in our campaign for access to Lorlatinib for all who need it, please get in touch with us.

And one last thing. We can only survive, and thrive, through working together. We are all volunteers, so if you’re interested in joining us and improving your own life, even for a few hours a week, please contact us.