1School of Medicine, UT Southwestern Medical Center, Dallas, Texas.
2Now with Department of Radiology, University of Washington, Seattle, Washington.
J Natl Compr Canc Netw. 2022 Jul;20(7):792-799.e4. doi: 10.6004/jnccn.2022.7017.
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.
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.
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.
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.
许多癌症患者曾患有癌症，因此可能被排除在临床试验之外。最近 NCI 的指导建议将这些患者纳入其中，尤其是当先前恶性肿瘤的风险对安全性或疗效终点几乎没有影响时。以乳腺癌为例，我们确定了这一政策变化对临床试验入组的潜在影响。
我们回顾了 1991 年至 2016 年期间 NCI 资助的乳腺癌临床试验方案。我们量化了与先前癌症相关排除标准的发生率，并使用 Fisher 精确检验评估了与试验特征的相关性。利用 SEER 数据，我们估计了乳腺癌患者中先前原发性（非乳腺癌）癌症诊断的发生率和时间。
在 87 项临床试验（总目标入组人数为 137253 人）中，77%的试验排除了有既往癌症的患者，最常见的是（79%）在过去 5 年内。在有影像学反应或毒性终点的试验中，69%的试验排除了既往癌症。在 SEER 数据中，先前（非乳腺癌）癌症诊断的发生率取决于乳腺癌分期，范围为 5.7%至 7.7%，其中 39%发生在乳腺癌发病后的 5 年内。对于排除既往癌症的试验，因这一原因而被排除的患者估计比例为 1.3%至 5.8%，被排除的患者估计人数为 1 至 288 人。
NCI 资助的乳腺癌临床试验中，超过四分之三的试验排除了有既往癌症的患者，包括近 70%的有反应或毒性终点的试验。鉴于超过 5%的乳腺癌患者有既往癌症史，在大型 III 期试验中，这种做法可能会排除数百名患者。根据最近 NCI 的入组标准，将有既往癌症史的患者纳入乳腺癌试验可能会对入组产生重大影响。
