The Therapeutic Goods Administration (TGA) has approved an updated indication for TRUQAP (capivasertib) following evaluation of additional clinical data submitted after the medicine’s initial registration.
In 2024, the TGA approved TRUQAP, in combination with fulvestrant, for the treatment of adult patients with hormone receptor (HR) positive, human epidermal growth receptor 2 (HER2) negative (defined as IHC 0 or 1+, or IHC 2+/ISH-) locally advanced or metastatic breast cancer following recurrence or progression on or after an endocrine based regimen. As a condition of registration, the sponsor was required to submit additional clinical data from the ongoing CAPItello-291 study as these results became available.
The TGA has now completed its assessment of updated efficacy and safety data, including longer-term follow-up and overall survival results. This assessment considered the totality of available evidence, including longer-term follow-up and analyses according to the presence or absence of alterations in the PIK3CA, AKT1 and PTEN genes.
At the time of the original approval, the available evidence supported a broad indication based on progression-free survival outcomes observed in the overall study population. This was supported by the Advisory Committee on Medicines, although their advice was provided before enough data were available to determine the treatment’s impact on overall survival. Since then, longer-term follow-up has provided greater clarity regarding which patients are most likely to benefit from treatment. The updated data indicate that the improvement in progression-free survival in the overall population was largely driven by patients whose tumours contained PIK3CA, AKT1 or PTEN pathway alterations. In patients confirmed not to have these alterations, the final overall survival analysis provided limited evidence of efficacy of capivasertib in combination with fulvestrant and raised concern for a potentially unfavourable survival outcome.
TRUQAP is associated with known treatment-related risks and adverse effects. In light of the updated efficacy data, the TGA concluded that, for patients whose tumours do not have PIK3CA, AKT1 or PTEN alterations, the available evidence no longer demonstrates that the expected benefits of treatment outweigh those risks. The revised indication therefore reflects the suspected lack of efficacy in this subgroup, together with the possibility of overall harm where treatment-related toxicity is not balanced by clear evidence of clinical benefit. Conversely, the benefit-risk balance remains favourable in patients with one or more of these alterations.
As a result, the TGA has approved an amendment to the approved indication to restrict use to patients with one or more PIK3CA, AKT1 or PTEN alterations. This update is based on additional clinical efficacy information and does not reflect any new safety concern with TRUQAP. The updated Product Information – external site includes the updated indication and additional safety data from longer-term follow-up, which remains consistent with the medicine’s established safety profile.
In reaching its decision, the TGA considered all available evidence, including mature overall survival data, expert clinical evaluation, previous Advisory Committee on Medicines advice, and the evolving understanding of the medicine’s effects in biomarker-defined patient populations. The revised indication aligns with the current approach taken by a number of comparable international regulators, which restrict use to patients with demonstrated PIK3CA/AKT1/PTEN pathway alterations.
Patients should speak with their treating healthcare professional if they have questions about what this change may mean for their treatment. Healthcare professionals should refer to the updated Product Information for full prescribing information and guidance regarding biomarker testing.
