Patients with metastatic breast cancer who received an oral formulation of paclitaxel had better response and survival and less neuropathy than patients who received intravenous paclitaxel, according to results of a phase III trial presented at by Umanzor et al at the San Antonio Breast Cancer Symposium (Abstract GS6-01). In this trial, researchers evaluated an oral form of paclitaxel, given in combination with encequidar, a p-glycoprotein pump inhibitor that allows the oral paclitaxel to be absorbed into the bloodstream.

“Oral administration of cancer chemotherapy is very important for … patients, especially in areas where patients have difficulty accessing infusion clinics regularly,” said the study’s lead investigator, Gerardo Antonio Umanzor Funez, MD, medical oncologist at Centro Oncologico Integral, who conducted the study with DEMEDICA of San Pedro Sula, Honduras.

Trial Methods

In this trial, researchers enrolled 402 patients with metastatic breast cancer. The patients were randomly assigned 2:1 to receive either 205 mg/m² of oral paclitaxel plus encequidar for 3 days a week, or 175 mg/ m² of paclitaxel intravenously every 3 weeks. Their tumors were evaluated for response and confirmed at two consecutive evaluations by a blinded, independent radiology company.

The primary endpoint was radiologically confirmed tumor response rate at two consecutive timepoints; secondary endpoints were progression-free survival and overall survival.

Findings

Results showed that 35.8% of the oral paclitaxel/encequidar group had a confirmed tumor response, compared with 23.4% in the intravenous paclitaxel group. In evaluating the prespecified modified intention-to-treat population, which excluded patients who did not have target tumors that could be evaluated by the central radiologist per Response Evaluation Criteria in Solid Tumors, version 1.1, or who did not receive sufficient treatments, the response rate was 40.4% for the oral paclitaxel/encequidar group and 25.6% for the intravenous paclitaxel group.

In measuring the durability of response, the researchers found that in 51% of the oral paclitaxel/encequidar group who had a confirmed response, the response lasted more than 150 days, compared with 38% of the intravenous paclitaxel group who had a response. Furthermore, a higher percentage of patients treated with oral paclitaxel/encequidar are continuing to receive the treatment.

Ongoing analysis of progression-free survival showed a median of 9.3 months for the oral paclitaxel/encequidar group, compared with 8.3 months for the intravenous paclitaxel group. Overall survival was 27.9 months for the oral paclitaxel/encequidar group compared with 16.9 months for the intravenous paclitaxel group.

The researchers said the oral paclitaxel/encequidar group reported higher rates of neutropenia, infection, and gastrointestinal side effects. They reported lower incidence and severity of neuropathy—17% vs 57% in the intravenous paclitaxel group. Grade 3 neuropathic symptoms were experienced by 1% of the patients in the oral paclitaxel/encequidar group vs 8% in the intravenous paclitaxel group.

“This oral form of paclitaxel provides a new therapeutic option for patients, in particular, for those who cannot easily travel,” explained Dr. Umanzor. “While blood counts still need to be monitored, oral administration allows patients to remain home during therapy and avoid spending significant time in the chemotherapy unit.

“We were pleasantly surprised that responses were durable, conferring an early survival advantage with minimal neuropathy,” he continued.

Dr. Umanzor said the next step will be testing the tolerability of oral paclitaxel in patients at high risk of developing peripheral neuropathy. The oral formulation may also be studied in other cancers, either as a monotherapy or in combination with other agents.

Dr. Umanzor also pointed out that while the study’s primary endpoint of confirmed tumor response was evaluated blindly, the study could not be blinded at the clinical site. This may have created bias in the reporting of adverse events, he explained. Also, the study was statistically powered only for confirmed response rate and not for the secondary endpoints.

Disclosure: The study was funded by Athenex. For full disclosures of the study authors, visit abstractsonline.com.