Historic evidence and future directions in clinical trial therapy of solid tumors

Area of Science:

• Oncology
• Clinical Trial Design
• Drug Approval

Background:

• Improved survival is the gold standard for oncologic therapy benefit.
• The U.S. Food and Drug Administration (FDA) accepts surrogate endpoints for drug approval.
• Tumor response (reduction in tumor size) is a common surrogate endpoint.

Purpose of the Study:

• To evaluate the appropriateness of tumor response as a surrogate endpoint in oncology.
• To examine the correlation between tumor response and improved survival in renal cell carcinoma.
• To assess the suitability of current endpoints for novel targeted therapies.

Main Methods:

• Review of clinical studies evaluating oncologic agents in renal cell carcinoma.
• Analysis of data on targeted therapies with cytostatic mechanisms.
• Discussion of the limitations of Response Evaluation Criteria in Solid Tumors (RECIST).

Main Results:

• Clinical studies have not consistently demonstrated a correlation between tumor response and improved survival in renal cell carcinoma.
• Tumor response may not be appropriate for evaluating targeted therapies acting via cytostatic mechanisms.
• Some patients with solid tumors may benefit from treatments that stabilize disease.

Conclusions:

• Tumor response is a complex surrogate endpoint with inconsistent correlation to survival in certain cancers.
• Current endpoints like RECIST may not be optimal for assessing novel cancer therapies.
• Diverse endpoints and trial designs are necessary for evaluating the benefits and risks of new oncologic treatments.