Truqap targets the treatment gap in second-line breast cancer

Limited treatment options remain after use of CDK4/6 Inhibitors… unmet needs persist for patients with genetic mutations

Secures evidence of 2.5-fold Improvement in PFS … Challenges in domestic access amid global reimbursement expansion

As the treatment gap after CDK4/6 inhibitors persists in HR+/HER2- metastatic breast cancer, precision treatment strategies targeting genetic mutations are emerging as a new alternative.

In particular, the AKT inhibitor Truqap (capivasertib) continues to gain global guideline recommendations and expanded reimbursement based on its clinical efficacy, leading to calls for its improved treatment access in Korea as well.

On the 14th, AstraZeneca Korea held the “Breast Cancer Precision Treatment Strategy Academy” in Seoul to mark the second anniversary of Truqap’s approval, and shared current treatment strategies and unmet needs in HR+/HER2- metastatic breast cancer.

Joohyuk Sohn, Professor of Medical Oncology at Yonsei Cancer Center

Currently, CDK4/6 inhibitors in combination with endocrine therapy have become the standard of care for first-line treatment of HR+/HER2- metastatic breast cancer. However, a significant number of patients experience disease progression due to resistance. The problem is that in the subsequent second-line setting, the actual available options are limited depending on patient characteristics and genetic mutations.

In particular, around half of these patients harbor mutations in PIK3CA, AKT1, or PTEN, which are regarded as major factors affecting disease progression and treatment response. As patients with these mutations have been reported to have a poorer prognosis compared to those without mutations, the need for targeted treatment strategies has been raised constantly.

The domestic environment also acts as a variable. Given the relatively high proportion of premenopausal patients in Korea, endocrine-based treatment options that can be used without ovarian suppression are limited, and there is strong demand for treatment strategies that allow patients to continue therapy while preserving quality of life.

In fact, after CDK4/6 inhibitor treatment, median progression-free survival (PFS) with endocrine monotherapy is only about two months, indicating limitations in treatment durability.

In this setting, Truqap is drawing attention as a treatment option that can target specific gene mutations. According to the Phase III CAPItello-291 study, Truqap plus fulvestrant improved median PFS to 7.3 months, about 2.5 times longer than fulvestrant alone, and reduced the risk of disease progression or death by 50% in patients with PIK3CA/AKT1/PTEN mutations.

This study is significant because it included a large number of patients with prior CDK4/6 inhibitor treatment experience, reflecting real-world clinical settings. Additionally, it demonstrated consistent treatment efficacy trends regardless of menopausal status and is therefore considered highly applicable to Korean patient populations as well.

In terms of safety, the regimen was shown to be manageable. In an analysis including patients with hemoglobin A1c (HbA1c) below 8%, the rate of grade 3 or higher hyperglycemia was 2.3%. Its clinical value stands out in that it enables a treatment strategy that considers quality of life while maintaining endocrine therapy-based treatment.

Currently, Truqap is recommended as a Category 1 option for second-line treatment in mutation-positive patients in the U.S. NCCN guidelines, and has also secured a high level of recommendation from the European Society for Medical Oncology (ESMO). It has already been reimbursed in eight countries, including the United States, the United Kingdom, Canada, and Australia.

By contrast, reimbursement has still not been granted despite nearly two years having passed since approval, and limitations in patient access remain. Although it was designated as a candidate for the Global Innovative products on Fast Track (GIFT) program, in acknowledgement of its therapeutic need and innovation, its actual use in clinical practice remains constrained.

Professor Joohyuk Sohn of the Department of Medical Oncology at Yonsei Cancer Center said, “There remains a gap in second-line treatment for HR+/HER2- metastatic breast cancer with gene mutations. We need to establish an institutional framework to ensure that treatments with proven clinical utility can actually be used in patient care.”