Oral Paclitaxel and Encequidar Improves PFS, OS in Metastatic Breast Cancer

A regimen of oral paclitaxel (Oraxol) and encequidar (oPac+E) led to improved progression-free survival (PFS) and overall survival (OS) than intravenous paclitaxel (IVPac) in metastatic breast cancer patients, suggest study updates presented at the 2020 San Antonio Breast Cancer Symposium (SABCS).¹

Taken alone, oPac is limited by poor bioavailability. But in combination with encequidar, the drug can be absorbed by the body and has demonstrated promising efficacy and clinical relevance.

According to the presentation, “oPac+E has the convenience of oral administration, has no risk of infusion reactions and has no need for infusion centers, which is especially important during the [coronavirus disease 2019] pandemic,” said lead author Gerardo Umanzor, MD. Notably, oPac+E carries less risk of neuropathy and alopecia, but higher risk of gastrointestinal adverse events and grade 4 neutropenia.

The spotlight poster presentation provides PFS and OS updates on results from the randomized, multinational KX-ORAX-001 trial (NCT02594371) presented at SABCS 2019 that showed oPac+E to have a 35.8% overall response rate (ORR) versus 23.4% ORR in IVPac patients. The update includes 14 additional months of data on the intent to treat (ITT) population comprising 402 patients randomized 2:1 to receive oPac+E (205 mg/m2 per day 3 times weekly) or a regimen of IVPac (175 mg/m2 every 3 weeks). A modified intent to treat population (mITT) included patients with RECIST measurable disease who received at least 7 days of oPac+E or 1 dose of IVPac (235 oPac+E; 125 IVPac).

In the oPac+E mITT group, median PFS was 8.4 months, compared with median 7.4 months in the IVPac mITT (HR, .739; P = 0.023). Median PFS in the ITT population given oPac+E was 8.4 months, and median PFS was 7.4 months in the IVPac ITT group (HR, .768; P = 0.046). Median OS was 23.3 months in the mITT oPac+E group vs 16.3 months in the mITT IVPac group (HR, .735; P = 0.026). In the ITT group, median OS in the oPac+E group and IVPac groups was 22.7 months and 16.5 months, respectively.

Overall, the combination met the primary efficacy end point, which was superiority in radiologic response when compared with IVPac at the dose and schedule approved for metastastic breast cancer. Another poster presented at SABCS 2020 demonstrated significantly lower rates of neuropathy in oPac compared with IVPac, which might allow patients to undergo therapy longer on the oral regimen while maintaining dose intensity and improving quality of life for patients.² Fewer patients required dose reductions, and none discontinued treatment in the oral regimen group vs 8% in the IVPac group.

In a spotlight poster discussion titled “Novel Therapeutics,” Cristina Saura Manich, MD, head of the Breast Cancer Unit of the Service of Medical Oncology at Vall d'Hebron University Hospital in Barcelona, discussed the updated findings regarding PFS and OS. She highlighted that 10% of patients in the trial were HER2-positive and that HER2 status was unknown in an additional 12% of the population, and that it has previously been established that weekly IVPac is more effective and less toxic than the tri-weekly schedule used in the study.

“I envision the main future challenges for this combination to be comparison with the standard weekly dose of IV paclitaxel in a pure HER2-negative population,” Manich said, “And report quality-of-life data, because oral regimens may be preferred from the patient’s perspective.”

Oral paclitaxel was the first oral taxane, a novel alternative to the standard IV chemotherapy, to elicit a higher overall response rate (ORR) than IVPac. The FDA granted oPac+E priority review in September 2020 with a prescription drug user fee act (PDUFA) date of February 28, 2021.³

References

1. Umanzor G, Rugo HS, Barrios FJ, et al. Oral Paclitaxel and Encequidar (oPac+E) versus IV paclitaxel (IVPac) in the Treatment of Metastatic Breast Cancer (mBC) Patients (Study KX-ORAX-001): Progression Free Survival (PFS) and Overall Survival (OS) Updates. Presented at: San Antonio Breast Cancer Symposium; December 8-11, 2020. Abstract PD1-08.

2. Rugo HS, Umanzor G, Barrios FJ, et al. Lower rates of neuropathy with Oral Paclitaxel and Encequidar (oPac+E) compared to IV Paclitaxel (IVPac) in treatment of metastatic breast cancer (mBC): Study KX-ORAX-001. Presented at: San Antonio Breast Cancer Symposium; December 8-11, 2020. Abstract PS13-06.

3. Slater H. FDA Grants Priority Review to Oral Paclitaxel, Encequidar Combo for Metastatic Breast Cancer. Cancer Network. September 1, 2020. Accessed December 10, 2020. https://www.cancernetwork.com/view/fda-grants-priority-review-to-oral-paclitaxel-encequidar-combo-for-metastatic-breast-cancer