Treatment with a combination of oral paclitaxel and encequidar resulted in higher confirmed tumor response rates in patients with metastatic breast cancer compared to intravenously administered paclitaxel, according to the results of a recent study. published.
The data — which was printed in the Journal of Clinical Oncology — also demonstrated that neuropathy, a side effect associated with weakness and pain in the hands and feet, was less common and less severe in patients who received the oral paclitaxel plus encequidar combination.
According to the study authors, taxane-based treatment regimens, such as paclitaxel, are among the most effective systemic therapies for early and advanced breast cancer.
However, they noted, these treatments must be given through a tube or needle inserted into a vein (intravenously). The problem with this method of administration, the researchers wrote, is that the risk of developing neuropathy is high.
Neuropathy, the study authors explain, is a major dose-limiting side effect associated with this method of treatment and can significantly affect a patient’s quality of life and limit their treatment options.
For these reasons, the study authors set out to assess the potential effects of treating patients with an orally administered chemotherapy regimen.
“Potential advantages make oral administration of paclitaxel attractive, including home administration, no need for (intravenous) access, and… no hypersensitivity reactions or need for corticosteroid and antihistamine prophylaxis,” they wrote.
Paclitaxel has low bioavailability when administered orally into a patient’s body, which means that a very small percentage of the initial drug reaches its target. But when oral paclitaxel is combined with encequidar, the drug may be better absorbed by the body – which is why the researchers decided to test this combination of two drugs.
The phase 3 study included 402 postmenopausal patients who were at least 18 years old. Participants were randomly assigned to receive either oral paclitaxel plus encequidar or intravenous paclitaxel.
The main objective of the study was to determine the confirmed tumor response rate (the percentage of patients whose disease decreases or disappears after treatment) in each group. The researchers also aimed to assess the duration of response (the time between treatment randomization and disease progression or death in patients whose disease initially responded to treatment) among the two treatment groups, as well as the overall survival (the time between treatment and death from any cause) and progression-free survival (the time between treatment and disease progression).
The results showed that there was a significant difference in terms of confirmed tumor response between the group that received the oral paclitaxel regimen (36%) and the intravenous paclitaxel group (23%).
In September 2020, seven patients remained on treatment with the combination versus one patient on intravenous paclitaxel monotherapy.
Combination therapy was also associated with a better median progression-free survival (8.4 months) than intravenously administered paclitaxel (7.4 months).
The median overall survival results were 22.7 months in the oral paclitaxel/encequidar group, versus 16.5 months in the intravenous paclitaxel group. However, the difference here was not statistically significant, meaning the researchers could not be sure if it was the treatment regimen that caused the improvement in overall survival time.
More patients in the combination group had to discontinue treatment within the first 10 weeks of starting the trial (26% versus 17%, respectively). The incidence of neuropathy, however, was significantly higher in the group that received intravenous paclitaxel. In fact, moderate or even worse neuropathy occurred in 31% of those who received only paclitaxel and 8% of those who received the combination.
In 2021, the Food and Drug Administration rejected the application for approval of oral paclitaxel plus encequidar, citing concern about a potential increased risk of developing neutropenia as a result of treatment or disease. It should be noted that neutropenia occurs when a person has an abnormally low number of white blood cells. When this happens, patients may be at higher risk of infection.
Investigators noted that this study was performed to support filing for registration for agency approval for the combination of oral paclitaxel and encequidar. They cautioned, however, that future studies should confirm these findings.
“Patients with elevated liver enzymes, serum bilirubin, or low serum albumin at study entry were at increased risk for early high-grade neutropenia and infectious complications, which in some cases were fatal,” writes the report. “Careful patient selection, use of growth factors and dose reductions as well as close monitoring of patients at increased risk are warranted. Further studies to optimize dosage in patients with hepatic dysfunction are warranted.
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