Alisertib in Combination With Weekly Paclitaxel in Patients With Advanced Breast Cancer or Recurrent Ovarian Cancer:...

Area of Science:

• Oncology
• Clinical Pharmacology

Background:

• Recurrent ovarian cancer presents a significant unmet medical need, necessitating novel therapeutic strategies to enhance progression-free survival (PFS) and overall survival.
• Current treatment paradigms for recurrent ovarian cancer require improvement, particularly in extending disease control duration.

Purpose of the Study:

• To evaluate the efficacy and safety of combining alisertib with weekly paclitaxel in patients with recurrent ovarian cancer.
• To assess the impact of this combination therapy on progression-free survival (PFS) compared to paclitaxel alone.

Main Methods:

• A randomized phase 2 clinical trial involving 142 patients with recurrent ovarian cancer.
• Patients were randomized to receive either alisertib plus paclitaxel or paclitaxel alone, stratified by platinum-free interval and prior taxane treatment.
• The primary endpoint was progression-free survival (PFS), with safety analyses conducted on the modified intention-to-treat (mITT) population.

Main Results:

• The combination of alisertib and paclitaxel demonstrated a median PFS of 6.7 months, compared to 4.7 months for paclitaxel alone (HR, 0.75; P=.14).
• Higher rates of grade 3 or higher drug-related adverse events were observed in the alisertib plus paclitaxel arm, including neutropenia and stomatitis.
• Adverse events leading to dose reductions were more frequent in the combination arm (74%) compared to the paclitaxel-alone arm (25%).

Conclusions:

• The combination of alisertib and paclitaxel showed a favorable trend in improving PFS for patients with recurrent ovarian cancer.
• Despite increased toxicity, the observed PFS benefit suggests that this combination warrants further investigation.
• The study highlights the potential of targeting pathways with alisertib in combination with chemotherapy for ovarian cancer treatment.