Seven point three months against 3.1. That gap, measured in how long women with advanced breast cancer lived before their disease worsened, is what carried capivasertib over the line at the US Food and Drug Administration.
The agency cleared the pill, sold by AstraZeneca as Truqap, on November 16, 2023. It is cleared in combination with fulvestrant for adults whose breast cancer is hormone receptor-positive and HER2-negative, locally advanced or metastatic, and whose tumor carries at least one alteration in the PIK3CA, AKT1 or PTEN genes. An FDA-approved test has to find that alteration. Eligible patients are those whose disease advanced on hormone-based therapy given for metastatic cancer, or whose cancer came back within a year after adjuvant treatment ended.
The trial behind it
The evidence comes from CAPItello-291, a randomized, double-blind, placebo-controlled study of 708 patients. Of those, 289 had tumors with one of the targeted alterations. Every participant had relapsed or progressed on an aromatase inhibitor, and up to one round of chemotherapy for advanced disease was allowed.
Patients received either 400 mg of capivasertib or a placebo twice a day for four days, followed by three days off. Both groups also got fulvestrant by injection, given on the first and fifteenth days of cycle 1 and every 28 days after that. Treatment ran until the cancer progressed or side effects became unacceptable.
In the 289-patient altered group, 155 people on capivasertib reached a median progression-free survival of 7.3 months. The 134 on placebo plus fulvestrant managed 3.1 months. The hazard ratio was 0.50. Across all 708 patients, the median was 7.2 months for the 355 in the capivasertib arm and 3.6 months for the 353 in the placebo arm, with a hazard ratio of 0.60.
One result tempers the headline. In an exploratory look at 313 patients without the alterations, the combination produced a numerical gain that did not reach statistical significance (hazard ratio 0.79). OncLive noted that the benefit in the full population was therefore driven mostly by the altered tumors. That is why the label is tied to genetic testing, and why the FDA also authorized FoundationOne CDx as the companion test.
Side effects
The list of common adverse reactions, reported by one patient in five or more, is long: diarrhea, skin reactions, higher random and fasting glucose, lower lymphocytes, hemoglobin, leukocytes and neutrophils, raised triglycerides and creatinine, nausea, fatigue, vomiting and stomatitis.
Tolerability was a real cost. Side effects forced dose interruptions in 34.9% of capivasertib patients versus 10.3% on placebo, and dose reductions in 19.7% versus 1.7%. Treatment was stopped for adverse events in 13.0% of the capivasertib group and 2.3% of the placebo group.
The recommended dose is 400 mg by mouth twice daily, roughly 12 hours apart, food optional. Four straight days on, three off, and the cycle repeats until the disease progresses or toxicity becomes unacceptable.
Sources
- Capivasertib with fulvestrant is approved by the USFDA for breast cancer treatment
- FDA Approves Capivasertib Plus Fulvestrant in Advanced HR+/HER2- Breast Cancer With PIK3CA, AKT1, or PTEN Alterations | OncLive
