Actionability of genomic alterations in the Molecular Screening and Therapeutics (MoST) program in New Zealand (NZ) depending on residence in NZ or Australia.

Abstract

e13763 Background: The Australian-led MoST program (ACTRN12616000908437 ) expands access to comprehensive genomic profiling (CGP) for rare, advanced, and treatment resistant cancers. CGP identifies actionable alterations to provide cancer patients with opportunities to access novel therapies through clinical trials. However, the actionability of alterations may depend on trial availability and local patterns of recruitment. This study compares whether CGP actionability for participants (pts) in the MoST-NZ cohort, would have differed if they lived in Australia. Methods: Pts enrolled in MoST-NZ who underwent successful CGP between 2021 and 2024 were included. Pts were discussed at a weekly joint Molecular Tumor Board (MTB) to define actionable alterations and recommend matched trials and targeted therapies. Data collection for the MoST-NZ cohort included pt demographics, actionable alterations, match for trials available in NZ and Australia, matches to targeted therapies, indication for germline genetic referrals, and barriers to trial access. Two analyses were conducted: a retrospective match of MoST-NZ pts to contemporaneous trial availability in NZ or Australia on the day of MTB presentation, using the MoST genomic-trial-matching database; and an audit of actual outcomes for the MoST-NZ pts. Results: The median age of the 190 MoST-NZ patients were 57.1 years (range 18–104), with majority being gastrointestinal (n = 50), sarcoma (n = 41), and gynaecological (n = 32) cancers. Analysis of c trial matching showed 141 (74.2%) of the MoST-NZ pts had alterations that would be matched to ≥1 trial in Australia, compared to 62 (32.6%) matched to NZ. This was similar to real world matching rate in the MoST-NZ cohort, with 51 (26.8%) pts matched to ≥1 trial. 46 of these 51 pts were matched to immunotherapy (IO) or combination IO trials, primarily based on tumor mutational burden (n = 20) and ARID1A loss (n = 20). Regarding final trial recruitment, 16 of the 51 pts (31.4%) were enrolled in trial that aligned with MTB recommendation; a similar recruitment rate previously reported in the Australian cohort (27.2%). The main barriers to trial recruitment in MoST-NZ were protocol ineligibility (n = 11), trial unavailability when eventually indicated (n = 9), clinical deterioration or pt preference (n = 7). Conclusions: CGP provides NZ pts with trial options beyond standard care, but CGP actionability is lower in NZ than Australia due to less availability of clinical trials. However, when trials are available, the rate of recruitment is similar in NZ. These findings underscore the intertwined value proposition between CGP and oncology trials. Locally, NZ would gain more value from CGP by increasing access to clinical trials.