Breakthrough for Breast Cancer Treatment
AstraZeneca, together with Astex Pharmaceuticals, has made significant strides in cancer treatment with the UK approval of Capivasertib. Known commercially as Truquap, it's the first of its kind—an AKT inhibitor—making it a groundbreaking advancement in the fight against hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer. This approval from the Medicines and Healthcare products Regulatory Agency (MHRA) follows closely on the heels of a nod from the U.S. FDA in November 2023.
What makes Capivasertib stand out is its precision approach in targeting the PI3K/AKT/mTOR pathway—a path often compromised in many cancer types. It affects all three AKT isoforms (AKT1, AKT2, AKT3) and is used in combination with fulvestrant for patients with genomic anomalies in the PIK3CA, AKT1, or PTEN genes. The drug's approval stems from the impressive results of the CAPItello-291 Phase III trial, which showcased a 40% decrease in disease progression risk when Capivasertib was paired with fulvestrant, compared to using fulvestrant alone. It's worth noting that 40% of trial participants had alterations in the PIK3CA/AKT1/PTEN pathway, highlighting Capivasertib's tailored mechanism for specific populations.
Revitalizing AKT Inhibition in Cancer Therapy
For years, AKT inhibitors faced hurdles, with some like Roche discontinuing their candidates. However, Capivasertib's entry could reignite interest in these inhibitors. Other companies, such as Taiho Pharmaceuticals with TAS-117 and Laekna with afuresertib, are also in the race, albeit in earlier stages of testing. For instance, afuresertib—acquired from GSK and Novartis—showed promising results in Phase II trials with a 30% objective response rate (ORR) and an 80% disease control rate, though its outcomes varied compared to Capivasertib.
AstraZeneca and Astex's partnership marks a strategic shift in enhancing existing cancer therapies, specifically aiming to bolster the efficacy of endocrine therapies and tackle resistance challenges. Capivasertib's dosing regimen—four days on, three days off—combined with its tolerable toxicity profile, positions it as a leading choice for clinicians.
This UK approval could pave the way for broader use of AKT inhibitors in cancers characterized by PI3K/AKT pathway interruptions, potentially providing lifelines where options are scarce. By stepping into this domain, Capivasertib opens doors for innovative treatments that could vastly improve the quality of life for countless patients.