Weighted Toxicity Score Evaluates Toxicity-to-Benefit Ratio of Cancer Therapies

A new tool, the weighted toxicity score (WTS), evaluates toxicity and enables interpretation of expected benefits vs costs of various cancer therapies, according to study results published in The Oncologist.

The WTS represents the total toxicity burden observed in a single arm of a randomized controlled trial. It can be graphed as a data pair with a metric of clinical outcome, such as progression-free survival (PFS) or response rate, in order to determine toxicity and efficacy, or cost vs benefit, of a given treatment. In this study, researchers aimed to confirm the utility of the WTS in various clinical trial contexts.

The WTS was first tested with aggregated data from 22 trials involving immune checkpoint inhibitors in lung cancer. In trials that compared immunotherapy alone to chemotherapy alone, for example, chemotherapy was found by WTS to be an average of 3.46 times as toxic as immunotherapy. Median PFS was superior for chemotherapy, whereas overall survival (OS) was superior with immunotherapy, consistent with data from the individual clinical trials.

The researchers then tested the WTS in individual trials. For instance, in the Keynote-042 trial (ClinicalTrials.gov Identifier: NCT02220894), which compared chemotherapy with pembrolizumab in non-small cell lung cancer, pembrolizumab was found be less toxic than chemotherapy (WTS of 2.03 vs 5.34, respectively). Pembrolizumab also had longer median PFS (10.3 vs 6.0 months) and OS (20.0 vs 12.2 months) than chemotherapy. Again, these results were consistent with the original study.

Finally, the researchers employed WTS with data from dose-finding trials. In the PROSELICA trial (ClinicalTrials.gov Identifier: NCT01308580), for example, researchers were able to determine by WTS that a 20 mg/m² dose of cabazitaxel has similar benefit and less toxicity than the approved dose of 25 mg/m².

“An important potential use of the WTS is to apply it prospectively while a trial is underway, to help investigators to identify excessive cumulative toxicity while the study is ongoing, and thus trigger dose reductions for individuals or groups of patients,” the researchers concluded. “The data could also be used by data safety monitoring boards to help make decisions about toxicity of a specific treatment in a clinical trial.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Jordan J, Maki RG. The weighted toxicity score: Confirmation of a simple metric to communicate toxicity in randomized trials of systemic cancer therapy. Oncologist. 2023;oyad192. doi:10.1093/oncolo/oyad192