Oral Paclitaxel Improves Response, Reduces Peripheral Neuropathy in Metastatic Breast Cancer

Patients with metastatic breast cancer who received an oral version of the chemotherapy drug paclitaxel with encequidar (Oral Paclitaxel) saw 14.8% improved response rates and 40% lower rates of peripheral neuropathy compared to those who took the drug intravenously (IV), according to the results of a new phase 3 clinical trial presented at the San Antonio Breast Cancer Symposium (SABCS).

“As an oncologist, it’s been very frustrating to have an effective chemotherapy like paclitaxel that a lot of patients cannot tolerate,” said the study’s lead investigator Dr. Gerardo Antonio Umanzor Funez, of the Centro Oncologico Integral in San Pedro Sula, Honduras, during a press conference at SABCS. “The therapy used in this phase 3 study — oral paclitaxel and encequidar – was designed to overcome this issue.”

In the pivotal phase 3, open-label, randomized trial, which was conducted at 45 sites in Central and South America, researchers enrolled 402 patients with metastatic breast cancer to evaluate paclitaxel given in combination with encequidar, a novel inhibitor that allows the oral form of the chemotherapy agent to be absorbed into the bloodstream.

Patients were randomly assigned to receive either 205mg/m² of Oral Paclitaxel for three consecutive days a week (taking roughly 11 tablets per day depending on their body size), or 175mg/m² of IV paclitaxel every three weeks.

Treatment with Oral Paclitaxel resulted in a significantly improved centrally confirmed response rate of 40.4%, compared with 25.6% with IV paclitaxel representing an absolute improvement of 14.8%. These results were further supported by a significant improvement in overall response with Oral Paclitaxel, with an absolute improvement of 12.4%. Additionally, tumor response in all clinically important subgroups was consistent with the overall confirmed response profiles.

Researchers also measured progression-free survival (PFS), the time from treatment to disease progression or worsening. When it came to PFS, they found a nonsignificant association between oral and IV paclitaxel, meaning the difference was not greater between the groups than what could be expected by chance.

Peripheral neuropathy, a condition that causes weakness, numbness and pain that typically occurs in the hands and feet, is a common side effect of treatment with IV paclitaxel, but rates were greatly reduced in patients who took the oral formulation. In the trial, 57% of patients who took IV paclitaxel were treated for peripheral neuropathy, while only 17% of patients in the oral formulation arm needed treatment.

While the two drugs’ toxicity profiles were similar, there were higher rates of neutropenia infection and gastrointestinal side effects in patients who took Oral Paclitaxel, but these were low grade and manageable, according to the authors.

Oral administration of cancer chemotherapy is important to patients and preferable to intravenous drugs, especially in areas where they have difficulty accessing infusion clinics regularly, Umanzor added. But the fact that the drug must be taken orally and that patients must fast while taking it was a shortcoming of the study. With treatment, Umanzor Funez explained, there is a four-hour fasting period prior to taking the first tablet of encequidar. After the patient waits an hour, they then take oral paclitaxel, followed by an additional hour of fasting afterward.

“I think this is going to be a limitation of this medication,” said Dr Virginia Kaklamani, co-director of SABCS and leader of the breast cancer program at the University of Texas Health in San Antonio. “Many of our patients may not be able to tolerate 11 tablets, but keep in mind it’s only for three days per week. That’s something we’ll take into consideration before we prescribe.”