Oral paclitaxel with encequidar improves overall survival and progression-free survival in breast cancer
USA: Compared to intravenous paclitaxel (IVpac), oral paclitaxel plus Encequidar (oPac + E) improved the confirmed tumor response while showing trends in overall survival (OS) and progression-free survival (PFS), says an article published in the Journal of Clinical Oncology.
Neuropathy makes intravenous paclitaxel more difficult to administer; therefore, premedication is necessary to avoid hypersensitivity-like symptoms. The new P-glycoprotein pump inhibitor encequidar (E), which is used to treat paclitaxel, improves oral absorption. In order to compare the effectiveness and safety of oPac + E once daily for three consecutive days per week with IVpac at the authorized dose and schedule, 175 mg/m2 once every three weeks in patients with mBC, Hope S. Rugo and colleagues conducted a phase III study.
With balanced demographics and past treatments, 400 Latin American patients (265 oPac + E, 137 IVpac) were included. The primary endpoint was determined by blinded independent central review and was confirmed by radiographic response using RECIST 1.1. Progression-free survival and overall survival were secondary endpoints.
The key findings of this study were as follows:
1. In comparison to 23% for IVpac, the confirmed response (intent-to-treat) for oPac + E was 36%.
2. The OS was 22.7 months as opposed to 16.5 months, and the PFS was 8.4 months as opposed to 7.4 months. 55% of oPac + E and 53% of IVpac adverse events were grade 3-4.
3. In comparison to IVpac, oPac + E had higher rates of nausea, vomiting, diarrhea, and neutropenic complications, especially in patients with elevated liver enzymes.
4. However, it had lower incidence and severity of neuropathy (2% v 15% > grade 2) and alopecia (49% v 62% all grades).
5. Treatment was a factor in 3% of on-study fatalities and 0% of on-study deaths (8% oPac + E vs. 9% IVpac).
In conclusion, oPac + E group increased the confirmed tumor response better than IVpac. The Authors also found that in oPac + E group, neuropathy was less common while neutropenic infections were more common in patients with increased liver enzyme levels at baseline.
Reference:
Rugo, H. S., Umanzor, G. A., Barrios, F. J., Vasallo, R. H., Chivalan, M. A., Bejarano, S., Ramírez, J. R., Fein, L., Kowalyszyn, R. D., Kramer, E. D., Wang, H., Kwan, M.-F. R., & Cutler, D. L. (2022). Open-Label, Randomized, Multicenter, Phase III Study Comparing Oral Paclitaxel Plus Encequidar Versus Intravenous Paclitaxel in Patients With Metastatic Breast Cancer. In Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.21.02953
