Abstract
Objective: To analyze all oncological trials using olaparib to create a complete risk/benefit profile of the drug.
Background: Novel chemotherapies in oncology are costly in capital and time investment for drug manufacturers. To maximize earnings, drug manufacturers may repurpose their medications for new indications in clinical trials. To fully understand the risk/benefits in comparison to a drug's efficacy, a pooled analysis must be conducted.
Methods: On May 25th, 2023, a search of Pubmed/MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for olaparib clinical trials used to treat solid cancers was conducted. We included clinical trials published in English that involved adult participants and focused on solid tumors. Screening and duplication occurred in a masked, duplicate fashion. Data extraction included trial and mutation characteristics, median progression-free survival and overall survival, adverse event rates, and objective response rates. Trials meeting their primary endpoint and safety criteria, were classified as positive. If trials failed to meet their endpoint or lacked prespecified primary endpoint, they were classified as negative or indeterminate, respectively.
Results: Olaparib was originally approved by the Food and Drug Administration for ovarian cancer but has since been tested across 41 different cancer indications. Cumulative risk increased with 6,085 grade 3-5 adverse events being reported in 9,848 participants while the objective response rate remained low at 24.6% and a median complete response of 0.4% since approval.
Conclusions: Excessive toxicity and meager progression-free survival in olaparib cancer trials are concerning regarding its ongoing utilization in new indications. Food and Drug Administration-approved treatment of ovarian cancer with olaparib was based on a 2014 study, but this approval has since been withdrawn. Considering the Food and Drug Administration-approval history observed throughout olaparib's lifetime, clinicians should carefully assess olaparib's risk-to-benefit profile when considering it as a therapy option.
Background: Novel chemotherapies in oncology are costly in capital and time investment for drug manufacturers. To maximize earnings, drug manufacturers may repurpose their medications for new indications in clinical trials. To fully understand the risk/benefits in comparison to a drug's efficacy, a pooled analysis must be conducted.
Methods: On May 25th, 2023, a search of Pubmed/MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for olaparib clinical trials used to treat solid cancers was conducted. We included clinical trials published in English that involved adult participants and focused on solid tumors. Screening and duplication occurred in a masked, duplicate fashion. Data extraction included trial and mutation characteristics, median progression-free survival and overall survival, adverse event rates, and objective response rates. Trials meeting their primary endpoint and safety criteria, were classified as positive. If trials failed to meet their endpoint or lacked prespecified primary endpoint, they were classified as negative or indeterminate, respectively.
Results: Olaparib was originally approved by the Food and Drug Administration for ovarian cancer but has since been tested across 41 different cancer indications. Cumulative risk increased with 6,085 grade 3-5 adverse events being reported in 9,848 participants while the objective response rate remained low at 24.6% and a median complete response of 0.4% since approval.
Conclusions: Excessive toxicity and meager progression-free survival in olaparib cancer trials are concerning regarding its ongoing utilization in new indications. Food and Drug Administration-approved treatment of ovarian cancer with olaparib was based on a 2014 study, but this approval has since been withdrawn. Considering the Food and Drug Administration-approval history observed throughout olaparib's lifetime, clinicians should carefully assess olaparib's risk-to-benefit profile when considering it as a therapy option.
| Original language | American English |
|---|---|
| State | Published - 21 Jul 2023 |
| Event | 7th Annual Joint Research Meeting: Biomedical, Biological, Neuroscience, Physiology, Forensics - Tandy Conference Center, Tulsa, United States Duration: 21 Jul 2023 → 21 Jul 2023 |
Conference
| Conference | 7th Annual Joint Research Meeting: Biomedical, Biological, Neuroscience, Physiology, Forensics |
|---|---|
| Abbreviated title | 7th Joint Annual Research Meeting |
| Country/Territory | United States |
| City | Tulsa |
| Period | 21/07/23 → 21/07/23 |