At its November 2025 meeting, the Pharmaceutical Benefits Advisory Committee (PBAC) considered a report on a ‘Monitoring system for updated overall survival results for cancer trials’. This report was prepared as part of a project on the Post-market Review Workplan.
Background
In July 2023, the PBAC considered a report reviewing the use of surrogate outcomes to inform PBAC recommendations for cancer medicines (the Cancer Surrogates Report). The Cancer Surrogates Report found that for submissions and resubmissions that presented interim or immature overall survival (OS) trial data between January 2012 to May 2022, around 60% had not subsequently published final trial results (60/101 trials). The Economic Sub-Committee (ESC) of the PBAC noted that OS results, where published, were generally consistent with interim results but expressed concern over potential publication bias in trials reporting final results.
In September 2023, the PBAC recommended a further project to develop a system to monitor final trial OS results for cancer medicines recommended by the PBAC and PBS listed. The Department contracted Monash University in June 2024 to undertake this work with the aim of highlighting if final trial OS results were consistent, better, or worse than the interim/immature results considered by the PBAC at the time of recommendation for PBS listing, and any issues with publication bias or reasons for results not being available.
Report
The ‘Monitoring system for final trial OS results for cancer medicines’ report is available below. Sections have been redacted to protect commercial-in-confidence material.
Summary
Pilot Study
A pilot study was conducted using data from PBAC submissions (n=24) from January 2012 to May 2022, reviewed during the Cancer Surrogates Report, where immature/interim OS data were used to support PBS listing and the pivotal trials (n=25) had not yet reported their final OS data at that time. Published literature were searched, and a broader search for other potential information sources, for final OS data on the included pilot trials between 3 June and 1 July 2024. Publications presenting updated OS data were identified for 21/25 (84%) trials, of which 13 publications were described as final reports. The high proportion of trials reporting updated and final OS data after being recommended by the PBAC indicated that implementing a system to prospectively monitor trials for additional OS data would be feasible.
Methods
Public Summary Documents (PSDs) and/or PBAC Minutes for cancer medicines recommended by the PBAC between June 2022 and March 2024 (inclusive) were reviewed. Trials for cancer medicines were included in the OS monitoring system if:
- the clinical claim relied upon surrogate outcome(s); and
- OS data were immature at the time of consideration; and
- the submission received a positive PBAC recommendation.
The relevant trial data were extracted and updated OS data were sought first from published literature. Clinical trial protocols and statistical analysis plans were checked for scheduled OS reporting timepoints for interim and final analyses and the trial definition of final OS. Any reported planned contamination points, such as crossover timepoints, in the trials were also identified. The searches included phase II/III trial results and any extended observational follow-ups from the included trials reporting OS outcomes. For trials that appeared to be completed but no final OS data were found, the Department requested this information from sponsors. Single-arm studies that were pivotal to the submissions’ clinical claims were also included; however, additional computation to assess comparative OS at later timepoints was beyond the scope of the report.
The final or updated OS results were then compared to the interim/immature OS data considered by the PBAC at the time of recommendation to confirm whether they align. A traffic light alert system was developed that included criteria related to whether the final OS Hazard Ratio (HR) was consistent, better or worse than the immature/interim HR; data maturity; and PBAC expectations for the final/updated OS HR. The alert system indicates when:
- further investigation of the evidence is recommended (red alert)
- continued monitoring of the trial is recommended (amber alert)
- the trial can exit monitoring (green alert).
Case reports were generated for each trial with a green or red alert for the PBAC to determine the next course of action.
Key Findings
Between June 2022 and March 2024 (inclusive), 18 submissions recommended by the PBAC relying on 21 trials (including 5 single-arm studies) reporting immature/interim OS data were included for further monitoring of OS data. The literature search identified updated OS data for 9/16 (56%) trials and 4/5 (80%) single-arm studies.
Three trials were identified for further investigation (red alert):
- ELEVATE-TN for acalabrutinib and PRIMA for niraparib - showed worse OS HR (difference of >0.1 towards the null) at subsequent data analysis which was considered likely to impact the primary clinical and cost-effectiveness or cost-minimisation analysis relied on in the respective PBAC submissions.
- COSMIC-311 for cabozantinib - no updated OS results were identified, and a 2024 publication claimed that further analyses on OS would not be conducted due to extensive crossover, hence, any future OS data are unlikely to be informative for decision-making purposes.
One trial was allocated to exit monitoring (green alert): SWOG 1500 trial for cabozantinib in renal cancer. The final OS analysis was mature (73%), and the OS HR was consistent with the interim result considered by the PBAC.
Of the five single-arm studies included in the monitoring system, 4 were allocated for continued monitoring (amber alert). One single-arm study (Study 101 for mobocertinib) was allocated for further investigation (red alert) but could exit the monitoring system as it was not PBS listed due to being withdrawn from the market.
ESC and PBAC Consideration
The Report was considered by the ESC in October 2025, and the PBAC in November 2025. The outcome for this item was published on 19 December 2025, as part of the November 2025 PBAC Outcomes.
The PBAC Minutes for this item are available below. Commercial-in-confidence material has been redacted.
The PBAC considered that following up on trial results to ensure that they aligned with the Committee’s expectations at the time of a positive recommendation was an important aspect of stewardship of the PBS and ensuring that PBS listings remain cost-effective. The PBAC considered that it would be worthwhile to continue the monitoring system for a further period before evaluating the merits of the system but noted that the relative priority of this project could be considered by the PBAC when reviewing the Post-market Review Workplan at a future meeting.
For trials allocated a red (further investigation) alert status, the PBAC considered that the relevant sponsors could be requested to provide further justification to support the current PBS listings. This could form part of any future work to continue the monitoring system undertaken as part of the Post‑market Review workplan. The PBAC considered that if the monitoring system were continued for an additional period, or any cost-effectiveness reviews were requested to be undertaken, sponsors would be informed through an update to the published PMR Workplan and would continue to be consulted on the project following standard PBAC processes and timelines.
The current Post-market Review Workplan is available on the Post-market Review website.