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A systematic review and meta-analysis of selected toxicity endpoints of alpelisib
Misty Shields1, Qianxing Mo2, Melissa Armitage3
1H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Purpose:
Alpelisib is a first-in-class α-specific phosphatidylinositol 3-kinase inhibitor approved for the treatment of patients with estrogen receptor-positive metastatic breast cancer. High absolute risk (AR) of relevant toxicities has been observed with this treatment. This meta-analysis aimed to improve the precision of the estimated AR of selected adverse events (AEs) associated with this new agent.
Materials And Methods:
A literature search was conducted in August 2019 to identify trials analyzing the anti-tumor efficacy and toxicity profile of alpelisib. Heterogeneity was assessed by using I 2 statistics. Data were analyzed using random effect meta-analyses for AR. Eleven trials and 511 patients were included.
Results:
There was no evidence of heterogeneity between studies regarding the AR of most AEs except for all-grade weight loss and grade 3-4 stomatitis. The number of serious AEs was clearly reported in only one study, of which the most common was hyperglycemia; the most common all-grade AEs were hyperglycemia (59%), diarrhea (56%), nausea (44%), and rash (38%). Grade 3/4 hyperglycemia and rash occurred in 28% and 10% of patients, respectively. No treatment-associated deaths were observed, and 18% of patients had to stop treatment due to toxicities.
Conclusions:
Alpelisib is associated with clinically relevant AEs that can lead to treatment discontinuation. The most common AE was hyperglycemia. No treatment-related deaths were observed.
Insights
Alpelisib treatment for metastatic breast cancer can cause significant adverse events (AEs), most commonly hyperglycemia. While no deaths occurred, 18% of patients discontinued treatment due to toxicities.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Alpelisib targets PI3Kα, approved for ER-positive metastatic breast cancer.
- Significant absolute risk (AR) of toxicities is associated with alpelisib treatment.
- Need for precise estimation of adverse event (AE) risks with alpelisib.
Purpose of the Study:
- To precisely estimate the absolute risk (AR) of specific adverse events (AEs) with alpelisib.
- To analyze the toxicity profile of alpelisib in patients with ER-positive metastatic breast cancer.
Main Methods:
- Systematic literature search conducted in August 2019.
- Meta-analysis of random effects for AR calculation.
- Inclusion of 11 trials with 511 patients.
Main Results:
- Hyperglycemia was the most frequent AE (59% all-grade, 28% grade 3/4).
- Other common AEs included diarrhea (56%), nausea (44%), and rash (38%).
- 18% of patients discontinued treatment due to toxicities; no treatment-related deaths observed.
Conclusions:
- Alpelisib is linked to clinically relevant AEs, frequently leading to treatment discontinuation.
- Hyperglycemia is the most common AE associated with alpelisib.
- Alpelisib treatment did not result in observed treatment-related deaths.
