Athenex Presents Updated Phase 3 Data on Survival and Tolerability Associated with Oral Paclitaxel and Encequidar in Patients with Metastatic Breast Cancer

Rhea-AI Summary

Athenex announced updated Phase 3 data at the 2020 San Antonio Breast Cancer Symposium (SABCS) showing the efficacy of oral paclitaxel versus IV paclitaxel in metastatic breast cancer patients. The median progression-free survival (PFS) for oral paclitaxel was 8.4 months compared to 7.4 months for IV (HR=0.739, p=0.023). Overall survival (OS) also favored oral treatment, with medians of 23.3 months versus 16.3 months (HR=0.735, p=0.026). Oral paclitaxel demonstrated a better safety profile with lower neuropathy rates. The FDA has granted Priority Review for this treatment, with a PDUFA date of February 28, 2021.

Positive

• Efficacy demonstrated: Oral paclitaxel shows median PFS of 8.4 months vs. 7.4 months for IV paclitaxel (HR=0.739, p=0.023).
• Overall survival improved: 23.3 months for oral paclitaxel vs. 16.3 months for IV paclitaxel (HR=0.735, p=0.026).
• Lower incidence of neuropathy: 22% for oral paclitaxel vs. 64% for IV.
• FDA Priority Review granted for oral paclitaxel with a PDUFA date of February 28, 2021.

Negative

• Overall survival data has a trend favoring oral paclitaxel but is not statistically significant (p=0.082).
• Incidence of gastrointestinal adverse events in the oral paclitaxel arm was initially higher before protocol amendments were made.

• Data presented at SABCS indicates benefits of oral paclitaxel and encequidar (oral paclitaxel) versus IV paclitaxel (IVP) on Progression-Free Survival (PFS) and on Overall Survival (OS), which supports superiority on the primary endpoint Overall Response Rate (ORR).
• In the intent-to-treat (ITT) population, oral paclitaxel showed a benefit on PFS versus IVP, and showed a trend favoring oral paclitaxel on OS versus IVP. Oral paclitaxel demonstrated a median PFS of 8.4 months vs. 7.4 months, hazard ratio (HR) 0.768 (95% CI: 0.584, 1.01), p=0.046. Oral paclitaxel demonstrated a median OS of 22.7 months vs. 16.5 months, HR 0.794 (95% CI: 0.607, 1.037), p=0.082.
• In the prespecified modified intent-to-treat (mITT) population, oral paclitaxel showed a benefit on both PFS and OS versus IVP. Oral paclitaxel demonstrated a median PFS of 8.4 months vs. 7.4 months, HR 0.739 (95% CI: 0.561, 0.974), p=0.023, and a median OS of 23.3 months vs. 16.3 months, HR 0.735 (95% CI: 0.556, 0.972), p=0.026.
• Additional data presented highlight a favorable tolerability profile, as measured by continued low incidence of neuropathy as well as manageable gastrointestinal side effects.

BUFFALO, N.Y., Dec. 09, 2020 (GLOBE NEWSWIRE) -- Athenex, Inc., (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer and related conditions, announced today the presentation of updated Phase 3 PFS and OS data demonstrating clinical benefits in efficacy and tolerability of oral paclitaxel versus IVP in patients with metastatic breast cancer (MBC). The findings further support the superiority of increased ORR observed with oral paclitaxel. These data were presented today during a spotlight poster presentation at the 2020 San Antonio Breast Cancer Symposium (SABCS).

“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 Dr. Johnson Lau, Chairman and Chief Executive Officer of Athenex. “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.”

The spotlight poster presentation at SABCS featured an update on PFS and OS data from the Phase 3 trial. In the prespecified modified intent-to-treat (mITT) population (n = 360), the median PFS data showed a benefit for oral paclitaxel versus IVP (8.4 vs. 7.4 months, respectively; hazard ratio [HR] = 0.739; 95% confidence interval [CI]: 0.561, 0.974; p = 0.023). Median OS data also showed a benefit for oral paclitaxel versus IVP (23.3 months vs. 16.3 months, respectively; HR = 0.735; 95% CI: 0.556, 0.972; p = 0.026).

In the intent-to-treat (ITT) population, which included all 402 randomized patients, the median PFS showed a benefit for oral paclitaxel versus IVP (8.4 months vs. 7.4 months, respectively; HR = 0.768; 95% CI: 0.584, 1.01; p = 0.046). The median OS data demonstrated a trend favoring oral paclitaxel versus IVP (22.7 months vs. 16.5 months, respectively; HR = 0.794; 95% CI: 0.607, 1.037; p = 0.082).

Updated safety analyses of up to 112 weeks continue to demonstrate the reduction in incidence and severity of neuropathy favoring oral paclitaxel versus IVP: all grades of neuropathy were 22% vs. 64%, and grade 3 neuropathy was 2% vs. 15%.

Also presented were data on the effect of prophylactic treatments on the incidence and severity of gastrointestinal-related adverse events. After approximately 30% of patients were enrolled, the Phase 3 trial protocol was amended to allow patients randomized to the oral paclitaxel arm to receive prophylactic pre-medications for gastrointestinal side effects. Overall gastrointestinal (GI)-related adverse events (AEs) were less frequent in the IV paclitaxel arm. GI-related AEs improved in the oral paclitaxel arm following the amendment, as measured by lower incidences of grade 2 vomiting before and after amendment (24% vs. 7%) and grade 2 diarrhea before and after amendment (27% vs. 16%).

“The oral paclitaxel regimen appears to overcome some of the limitations of IV therapy, particularly in terms of reducing the risk of neuropathy,” commented lead investigator Gerardo Antonio Umanzor Fúnez, M.D., a medical oncologist at Centro Oncologico Integral, working with DEMEDICA of San Pedro Sula, Honduras. “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.”  

Oral paclitaxel has been granted Priority Review by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic breast cancer with a PDUFA date of February 28, 2021.

About the Phase 3 Oral Paclitaxel and Encequidar Clinical Trial
The Phase 3 trial randomized 402 patients with any metastatic breast cancer subtypes in a 2:1 ratio to receive either the oral paclitaxel regimen (205 mg/m² of oral paclitaxel plus 15 mg of encequidar) for three days a week or the approved IV paclitaxel regimen (175 mg/m²) as a three-hour infusion every three weeks. The primary efficacy endpoint was overall response rate (ORR) confirmed at two consecutive timepoints by a blinded, independent radiology review that used RECIST v1.1 criteria to evaluate patients’ tumors for response. The trial was designed to demonstrate superiority of oral paclitaxel over IVP on the primary end point of ORR. Secondary endpoints included progres

FAQ

What are the key findings from Athenex's Phase 3 trial presented at SABCS regarding oral paclitaxel (ATNX)?

The Phase 3 trial showed that oral paclitaxel improved median progression-free survival (PFS) to 8.4 months and overall survival (OS) to 23.3 months compared to IV paclitaxel.

What is the significance of the FDA Priority Review for Athenex's oral paclitaxel?

The FDA Priority Review indicates a fast-tracked evaluation process for oral paclitaxel, with a decision expected by February 28, 2021, which could significantly impact its market availability.

How does the tolerability of oral paclitaxel compare to IV paclitaxel based on recent data?

Oral paclitaxel has shown a lower incidence of neuropathy (22% vs. 64%) and manageable gastrointestinal side effects, indicating better tolerability.

What are the implications of the trial results for patients with metastatic breast cancer?

The trial results suggest that oral paclitaxel could offer a more effective and tolerable treatment option compared to IV paclitaxel, potentially transforming treatment paradigms.