Clinical Trial Accrual at Initial Course of Therapy for Cancer and Its Impact on Survival

Abstract

Background: This retrospective cohort study sought to characterize the accrual of patients with cancer into clinical trials at the time of diagnosis and analyze the impact of accrual on survival. Methods: The National Cancer Database (NCDB) was queried for patients enrolled in clinical trials at their initial course of treatment for 46 cancers from 2004 through 2015. Descriptive statistics were used to characterize the accrual of patients with cancer in clinical trials at diagnosis, and Kaplan-Meier graphical displays, log-rank tests, odds ratios, and stratified Cox proportional hazards models were used to analyze the impact of accrual on overall survival (OS). Strata were defined using 10 variables. Model-based adjusted survival curves of 2 groups were reverse-generated based on a Weibull distribution. Results: Of 12,097,681 patients in the NCDB, 11,576 (0.1%) were enrolled in trials. Patients in clinical trials typically had metastatic disease (30.9% vs 16.4%; P<.0001), were white (88.0% vs 84.8%; P<.0001), had private/managed care insurance (56.4% vs 41.8%; P<.0001), had fewer comorbidities (Charlson-Deyo score 0: 81.9% vs 75.7%; P<.0001, and Charlson-Deyo scores 1–3: 18.1% vs 24.3%; P<.0001) compared with those not in trials. At a median follow-up of 64 months, enrollment in a clinical trial was associated with improved OS in univariate and stratified analyses, with a median survival of 60.0 versus 52.5 months (hazard ratio, 0.876; 95% CI, 0.845–0.907; P<.0001). Stratified analysis with matched baseline characteristics between patients enrolled and not enrolled in a clinical trial showed superior OS at 5 years (95.0% vs 90.2%; P<.0001). Conclusions: Enrollment in clinical trials at first line of therapy in the United States is exceedingly low and favors young, healthy, white patients with metastatic disease and private insurance who are treated at academic medical centers. Patients with cancer treated in clinical trials live longer than those not treated in trials.

Impact of radiation therapy facility volume on survival in patients with cancer

“…It has been shown that adhering to radiation therapy protocol guidelines impacts patient outcomes, 29,30 and clinicians treating a larger number of patients may be more likely to comply with guidelines. Second, facility volume may be a surrogate for services provided by the entire facility, such as supportive care services or clincial trial accrual 31,32 . For instance, higher volume centers may be better equipped to manage side effects from treatment, resulting in improved patient outcomes, and better oncological services, in general, would result in more favorable outcomes for patients.…”

Clinical trial risk in leukemia: Biomarkers and trial design

“…Correspondingly, physicians must also support enrollment in trials exploring new lines of therapy. Zaorsky et al found that enrollment in clinical trials at first‐line therapy in the US is exceedingly low at 0.1% of cancer patients, despite data showing patients with cancer treated in clinical trials live longer than those not treated in trials 22 . These results indicate that physicians and drug development must balance both probability and value of success when selecting line of therapy, albeit potential increased cost, difficulty, and/or risk.…”

Authors’ Reply: To the Letter to the Editor by Kessel et al

“…Several studies have shown that surgeon volume, rather than hospital volume, is an important factor. 4 Another study supported the evidence that lower-volume hospitals with excellent resources have similar results as high-volume centers. 5 Furthermore, in a large study evaluating the impact of volume on pancreatic cancer results, despite its conclusion, found differences only when comparing hospitals with as little as 5 versus 50 cases annually.…”

“…Figure 1 in our article shows limited numbers for many practices performing surgeries on the brain, pancreas, and esophagus. Overall facility surgical volume may be a better composite quality metric that is a surrogate for other quality metrics, such as availability of clinical trials 4 or presence of cardio-oncology clinics, 5,6 which may also improve survival.…”