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The Role of Neoadjuvant Trials in Drug Development for Solid Tumors
Samuel A Funt1, Paul B Chapman2
1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Abstract:
The relatively low success rate of phase II oncology trials in predicting success of novel drugs in phase III trials and in gaining regulatory approval may be due to reliance on the endpoint of response rate defined by the RECIST. The neoadjuvant treatment paradigm allows the antitumor activity of a novel therapy to be determined on a pathologic basis at the time of surgery instead of by RECIST, which was not developed to guide clinical decision making or correlate with long-term outcomes. Indeed, the FDA endorsed pathologic complete response (pCR) as a surrogate for overall survival (OS) in early-stage breast cancer and granted accelerated approval to pertuzumab based on this endpoint. We propose that pCR is a biologically rational method of determining treatment effect that may be more likely to predict OS. We discuss some advantages of the neoadjuvant trial design, review the use of neoadjuvant therapy as standards of care, and consider the neoadjuvant platform as a method for drug development. Clin Cancer Res; 22(10); 2323-8. ©2016 AACR.
Insights
Pathologic complete response (pCR) in neoadjuvant oncology trials may better predict long-term outcomes than RECIST. This approach offers a more biologically rational assessment of treatment efficacy for novel drug development.
Area of Science:
- Oncology
- Clinical Trials
- Drug Development
Background:
- Phase II oncology trials often have low success rates in predicting Phase III outcomes and regulatory approval.
- Reliance on RECIST (Response Evaluation Criteria in Solid Tumors) for assessing treatment efficacy may be a contributing factor.
- RECIST was not designed for clinical decision-making or correlating with long-term patient survival.
Purpose of the Study:
- To propose pathologic complete response (pCR) as a more reliable endpoint in neoadjuvant oncology trials.
- To highlight the advantages of the neoadjuvant treatment paradigm for evaluating novel therapies.
- To advocate for the neoadjuvant platform as a superior method for drug development and assessing treatment effect.
Main Methods:
- Evaluating antitumor activity based on pathologic assessment at surgery, rather than RECIST.
- Reviewing the FDA's endorsement of pCR as a surrogate for overall survival (OS) in early-stage breast cancer.
- Analyzing the benefits of the neoadjuvant trial design for drug development.
Main Results:
- Pathologic complete response (pCR) is a biologically rational method for determining treatment effect.
- pCR may be a more accurate predictor of overall survival (OS) compared to RECIST.
- The neoadjuvant approach allows for direct assessment of treatment impact on tumor tissue.
Conclusions:
- The neoadjuvant treatment paradigm, using pCR, offers a more robust method for evaluating novel oncology drugs.
- pCR serves as a valuable surrogate endpoint, potentially improving the success rate of drug development.
- The neoadjuvant platform facilitates better clinical decision-making and prediction of long-term outcomes in cancer therapy.
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