Potential Impact of Revised NCI Eligibility Criteria Guidance: Prior Malignancy Exclusion in Breast Cancer Clinical Trials

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  • 1 School of Medicine, UT Southwestern Medical Center, Dallas, Texas;
  • | 2 Now with Department of Radiology, University of Washington, Seattle, Washington;
  • | 3 School of Public Health, University of Texas Health Science Center at Houston, Dallas, Texas; and
  • | 4 Department of Population and Data Sciences,
  • | 5 Harold C. Simmons Comprehensive Cancer Center,
  • | 6 Department of Internal Medicine, and
  • | 7 Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, Texas.

Background: Many individuals with cancer have survived a prior cancer and for this reason may have been excluded from clinical trials. Recent NCI guidance recommends including these individuals, especially when the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low. Using breast cancer as an example, we determined the potential effect this policy change may have on clinical trial accrual. Patients and Methods: We reviewed protocols of NCI-sponsored breast cancer clinical trials activated in 1991 through 2016. We quantified prevalence of prior cancer-related exclusion criteria and assessed the association with trial characteristics using Fisher’s exact tests. Using SEER data, we estimated the prevalence and timing of prior primary (nonbreast) cancer diagnoses among patients with breast cancer. Results: Among 87 clinical trials (total target enrollment, 137,253 patients), 77% excluded individuals with prior cancer, most commonly (79%) within the preceding 5 years. Among trials with radiographic response or toxicity endpoints, 69% excluded prior cancer. In SEER data, the prevalence of a prior (nonbreast) cancer diagnosis ranged from 5.7% to 7.7%, depending on breast cancer stage, of which 39% occurred within 5 years of the incident breast cancer. For trials excluding prior cancer, the estimated proportion of patients excluded for this reason ranged from 1.3% to 5.8%, with the estimated number of excluded patients ranging from 1 to 288. Conclusions: More than three-fourths of NCI-sponsored breast cancer clinical trials exclude patients with prior cancer, including almost 70% of trials with response or toxicity endpoints. Given that >5% of patients with breast cancer have a history of prior cancer, in large phase III trials this practice may exclude hundreds of patients. Following recent NCI eligibility guidance, the inclusion of patients with prior cancer on breast cancer trials may have a meaningful impact on accrual.

Submitted March 1, 2022; final revision received March 31, 2022; accepted for publication March 31, 2022.

Author contributions: Study concept and design: Pruitt, Gerber. Data collection: Perez. Statistical analysis: Murphy, Pruitt. Data interpretation: Murphy, Pruitt, Rashdan, Rahimi, Gerber. Manuscript preparation: Perez, Murphy, Pruitt, Gerber.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: This work was supported by NCI Midcareer Investigator Award in Patient-Oriented Research (K24 CA201543-01; D.E. Gerber) and R01CA229834-02 (S.L. Pruitt).

Correspondence: David E. Gerber, MD, Division of Hematology-Oncology, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Mail Code 8852, Dallas, TX 75230-8852. Email: david.gerber@utsouthwestern.edu

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