One step forward, two steps back: The story of everolimus in advanced breast cancer
Saroj Niraula1, Alberto Ocana2, Eitan Amir3
1Department of Medical Oncology and Hematology, CancerCare Manitoba and University of Manitoba, Winnipeg, MB, R3E 0V9, Canada.
Abstract:
There has been a substantial surge of 'targeted agents' in contemporary anticancer drug armamentarium and some of these agents have revolutionized the outcome of cancer patients. However, on contrary to the nomenclature, not all new targeted agents are selected based on presence of target molecules on the cancer cells. Drugs are typically approved based on demonstration of benefit in randomized controlled trials with regards to efficacy outcomes although both the 'benefits' and 'outcomes' are defined inconsistently. Surrogates that are not validated properly are often used as endpoints. Furthermore, new anticancer drugs are frequently associated with increased inconvenience to the patients and/or to the society due to added toxicity and cost. In this perspective article, emphasis is given to the above problems focusing on room for improvement in anticancer drug development. An illustration of a recently approved drug to treat advanced breast cancer, everolimus and a previously revoked drug bevacizumab is given.
Insights
New targeted anticancer drugs show promise but face challenges in development. Improved validation of benefits and outcomes is crucial to enhance patient care and reduce costs associated with novel cancer therapies.
Area of Science:
- Oncology
- Pharmacology
- Drug Development
Background:
- The field of oncology has seen a significant increase in targeted anticancer agents.
- While some targeted agents have improved patient outcomes, their selection and approval processes present challenges.
- Inconsistent definitions of benefits and outcomes, along with the use of unvalidated surrogate endpoints, complicate drug evaluation.
Purpose of the Study:
- To highlight critical issues in the development of targeted anticancer drugs.
- To emphasize the need for improved validation of efficacy endpoints and patient-reported outcomes.
- To discuss the societal and patient-related burdens of new anticancer therapies, including toxicity and cost.
Main Methods:
- This perspective article critically analyzes current practices in anticancer drug development.
- It examines the challenges associated with the approval and utilization of targeted agents.
- Case examples of everolimus (approved) and bevacizumab (revoked) are used to illustrate key points.
Main Results:
- Targeted agents are not always selected based on the presence of specific molecular targets.
- Drug approval often relies on randomized controlled trials with inconsistently defined efficacy outcomes.
- New anticancer drugs frequently introduce additional toxicity and financial costs for patients and society.
Conclusions:
- There is a significant need for improvement in the anticancer drug development pipeline.
- More rigorous validation of surrogate endpoints and consistent definitions of clinical benefits are required.
- Addressing toxicity and cost is essential for sustainable advancement in cancer treatment.
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