Assessing Patient Risk, Benefit, and Outcomes in drug development: Over a Decade of Ado-Trastuzumab Clinical Trials

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Abstract

Objective: Our study aims to examine risk/benefit profiles of all published clinical trials assessing efficacy of ado-trastuzumab emtansine (T-DM1).

Background: FDA approval for drug development is time-consuming and costly. Around 90% of trials fail for lack of clinical efficacy, causing undue treatment burden on patients. Therefore, determining a drug's risk/benefit profile can mitigate risks and improve quality of life.

Methods: On May 26th, 2023, investigators conducted a literature search for clinical trials using T-DM1 as monotherapy or combination with other therapies for cancer treatment. Inclusion criteria for study extraction included clinical trials published in English, containing adult subjects, involving solid tumors. Screening and data extraction was performed in masked, duplicate fashion. In each eligible study, we gathered trial characteristics, adverse event data, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Trial outcome was considered positive when meeting primary endpoint and safety, indeterminate (safe but no prespecified primary endpoint), or negative, when not meeting either criteria.

Results: Of 39 clinical trials, T-DM1 was tested in 7 cancer indications, 1 having FDA approval. Clinical testing beyond T-DM1's initial indication revealed a decline in drug efficacy and a rise in cumulative adverse events. In total, 3,403 Grade 3-5 adverse events were reported across 7,661 trial participants. Off-label testing across all indications exhibited variable ORR (5.6-44.4%), median OS (8.2-28.9 months), and median PFS (2.4-7.2 months). Clinical trial outcomes became increasingly negative after approval.

Conclusion: Our results demonstrated a risk/benefit profile of modest quality for breast cancer, however, the risks dramatically increased for all off-label indications, with little benefit. Future physicians using T-DM1 as a therapy should cautiously evaluate the risks and benefits of its effect on patients.
Original languageAmerican English
StatePublished - 21 Jul 2023
Event7th Annual Joint Research Meeting: Biomedical, Biological, Neuroscience, Physiology, Forensics - Tandy Conference Center, Tulsa, United States
Duration: 21 Jul 202321 Jul 2023

Conference

Conference7th Annual Joint Research Meeting: Biomedical, Biological, Neuroscience, Physiology, Forensics
Abbreviated title7th Joint Annual Research Meeting
Country/TerritoryUnited States
CityTulsa
Period21/07/2321/07/23

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