AstraZeneca's Truqap Gets FDA Approval for Combined Breast Cancer Treatment

The FDA approved AstraZeneca's Truqap (capivasertib) combined with Faslodex for advanced HR-positive, HER2-negative breast cancer in patients with specific biomarkers. This approval, based on the CAPItello-291 trial, demonstrated a 50% reduction in disease progression or death compared to Faslodex alone.

FDA Approval Marks a Milestone

In a landmark decision, the U.S. Food and Drug Administration (FDA) has approved novel AKT inhibitor, Truqap (capivasertib), in combination with the endocrine therapy Faslodex (fulvestrant), for the treatment of certain advanced breast cancer cases. This approval, however, comes with specific biomarker-based restrictions, signaling a more targeted approach in cancer therapy.

Truqap is the first of its kind, an AKT inhibitor targeting tumors with alterations in the PIK3CA, AKT1, or PTEN genes. These genetic markers are notably prevalent in advanced HR-positive breast cancer, affecting up to 50% of patients. 

The Breakthrough of Truqap

The drug's effectiveness was underscored in the CAPItello-291 Phase III trial, where it demonstrated a 50% reduction in the risk of disease progression or death compared to Faslodex alone in the biomarker-altered population.

The CAPItello-291 was a randomized, double-blind, placebo-controlled, multicenter trial involving 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer. Of these patients, 289 had tumors with PIK3CA/AKT1/PTEN alterations. All patients were required to have experienced progression on aromatase inhibitor-based treatment.

However, the FDA’s restriction to this biomarker-altered population has sparked some disappointment. The CAPItello-291 trial had demonstrated significant benefits of the Truqap-Faslodex combination in a broader patient pool, irrespective of mutation status. In the broader trial population, the combination still improved progression-free survival by 21%, raising questions about the FDA's restrictive approach based on overall survival metrics.

The trial's major efficacy outcome was progression-free survival (PFS), and the results were compelling. Patients treated with Truqap and Faslodex showed a median PFS of 7.3 months, significantly higher than the 3.1 months observed in the placebo group.

Komal Jhaveri, MD, Medical Oncologist, Memorial Sloan Kettering Cancer Center, said: 

“Patients with advanced HR-positive breast cancer typically experience tumour progression or resistance with widely used first-line endocrine therapies and there is an urgent need to extend the effectiveness of these approaches. The combination of capivasertib and fulvestrant, a first-of-its-kind combination, provides a much-needed new treatment option for up to half of patients in this setting with these specific biomarkers, offering the potential to delay disease progression and provide more time with their disease under control.”

A Comprehensive Treatment Landscape

AstraZeneca's commitment to combating breast cancer is further exemplified by its diverse portfolio, including the recently approved Enhertu for HER2-positive breast cancer and ongoing trials like CAPItello-290 for triple-negative breast cancer. Truqap's addition to this arsenal represents a significant advancement in personalized cancer therapy.

The global implications of Truqap’s approval are vast, with regulatory agencies in countries like Brazil, Canada, Israel, Australia, the U.K., Singapore, and Switzerland currently reviewing the combination. The European Union, China, and Japan are also considering regulatory applications.

As AstraZeneca and the global medical community await further overall survival data from the CAPItello-291 trial, there remains potential for expanding Truqap's label. This progression signifies a critical juncture in the evolving narrative of precision medicine and targeted cancer treatments, paving the way for more personalized and effective therapies.

David Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, remains optimistic, noting that AKT alterations are present in about half of HR-positive breast cancer cases. 

 “As a first-in-class medicine, this approval provides a critical new option for patients in the US with this specific type of disease and we look forward to bringing Truqap to the many breast cancer patients who can benefit across the globe.”

In conclusion, Truqap’s approval marks a significant milestone in the fight against breast cancer, offering new hope for patients with specific genetic profiles. As the medical community continues to delve into the intricacies of cancer genomics, treatments like Truqap are expected to play a pivotal role in shaping future cancer therapy paradigms.