Updated phase 3 progression-free survival and overall survival data demonstrated clinical benefits in efficacy and tolerability of oral paclitaxel and encequidar versus intravenous paclitaxel in patients with metastatic breast cancer.
Updated phase 3 progression-free survival (PFS) and overall survival (OS) data demonstrated clinical benefits in efficacy and tolerability of oral paclitaxel and encequidar (oral paclitaxel) versus intravenous paclitaxel (IVP) in patients with metastatic breast cancer (MBC), according to a poster presentation at the 2020 San Antonio Breast Cancer Symposium (SABCS).
The researchers explained in the presentation that the study results support the superiority of the increased overall response rate found with oral paclitaxel.
“Having previously presented superior efficacy on overall response rate and favorable tolerability versus IV paclitaxel at SABCS 2019, it is gratifying to report that our pivotal phase 3 trial continues to show sustained efficacy and manageable adverse events with oral paclitaxel and encequidar,” said Johnson Lau, MBBS, MD, FRCP, board chairman and chief executive officer of Athenex, in a press release. “The updated phase 3 PFS and OS data further support the clinical rationale for oral paclitaxel as an efficacious and tolerable treatment option for people living with metastatic breast cancer.”
In the data presented at SABCS 2020, the prespecified modified intent-to-treat (mITT) population demonstrated that oral paclitaxel had a median PFS of 8.4, while the IVP PFS was 7.4 months, showing the benefit of oral paclitaxel as treatment. Additionally, the median OS data also supported the benefit of oral paclitaxel, as the median OS for oral paclitaxel was 23.3 months and the median OS for IVP was 16.3 months.
Among the intent-to-treat (ITT) population, the median PFS for oral paclitaxel was observed to be 8.4 months while IVP was 7.4 months. For the median OS data, oral paclitaxel was also preferable to IVP, at 22.7 months versus 16.5 months, respectively.
Additionally, the updated safety analyses conducted over approximately 112 weeks further showed oral paclitaxel had a greater reduction in incidence and severity of neuropathy in comparison with IVP. For oral paclitaxel, all grades of neuropathy were 22% and for IVP were 64%, while grade 3 neuropathy was 2% versus 15%, respectively.
The data from the study also demonstrated the incidence and severity of gastrointestinal-related adverse events (AEs) for oral paclitaxel and IVP. During the study, the researchers amended the trial protocol so that patients would be randomized to the oral paclitaxel arm to receive prophylactic pre-medications for gastrointestinal side effects.
Before the study was randomized, the data demonstrated that overall gastrointestinal (GI)-related AEs occurred less frequently in the IV paclitaxel arm. However, GI-related AEs improved in the oral paclitaxel arm following the randomization, which was observed through the lower incidences of grade 2 vomiting before and after the amendment (24% versus 7%) and grade 2 diarrhea before and the after amendment (27% versus 16%).
“The oral paclitaxel regimen appears to overcome some of the limitations of IV therapy, particularly in terms of reducing the risk of neuropathy,” said lead investigator Gerardo Antonio Umanzor Fúnez, MD, a medical oncologist at Centro Oncologico Integral, in a press release. “The lessened burden of neuropathy, the ability to manage GI side effects with prophylactic treatments, and the convenience of home-based administration, could be transformational in the treatment of metastatic breast cancer, especially in the current environment.”
Following these updated study results, oral paclitaxel was granted priority review by the FDA for the treatment of MBC with a prescription drug user fee act date set for February 28, 2021.
Athenex Presents Updated Phase 3 Data on Survival and Tolerability Associated with Oral Paclitaxel and Encequidar in Patients with Metastatic Breast Cancer. Buffalo, NY: Athenex, Inc; December 9, 2020. globenewswire.com/news-release/2020/12/09/2142247/0/en/Athenex-Presents-Updated-Phase-3-Data-on-Survival-and-Tolerability-Associated-with-Ora%E2%80%A6. Accessed December 18, 2020.