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Overcoming barriers to clinical trial enrollment in patients with bone and soft tissue sarcoma: a paradigm for an increasingly heterogeneous cancer population

The Sarcoma Journal. 2019 December;3(4):8-20
December 13, 2019|The Sarcoma Journal
Ari Rosenberg, MD;Sheetal Kircher, MD;Elizabeth A. Hahn, MA;Karl Bilimoria, MD, MS;Jeffrey D. Wayne, MD;Alfred Rademaker, PhD;Al Benson III, MD;John Hayes, MD;Terrance Peabody, MD;Samer Attar, MD;Mark Agulnik, MD
Author and Disclosure Information

Ari Rosenberg, MD,a Sheetal Kircher, MD,a,b Elizabeth A. Hahn, MA,b,c,d Karl Bilimoria, MD, MS,b,d,e Jeffrey D. Wayne, MD,b,e,f Alfred Rademaker, PhD,b,c Al Benson III, MD,a,b John Hayes, MD,b,g Terrance Peabody, MD,b,h Samer Attar, MD,b,h Mark Agulnik, MDa,b                                                                                                                                      aDivision of Hematology and Oncology, Department of Medicine, Feinberg School of Medicine of Northwestern University; bRobert H. Lurie Comprehensive Cancer Center, Northwestern University; cDepartment of Preventive Medicine, Feinberg School of Medicine of Northwestern University; dNorthwestern Institute for Comparative Effectiveness Research in Oncology (NICER-Onc), Lurie Comprehensive Cancer Center, Northwestern Medicine, Northwestern University; eDepartment of Surgery, Northwestern University; fDepartment of Dermatology, Northwestern University; gDepartment of Radiation Oncology, Northwestern University; and hDepartment of Orthopedic Surgery, Northwestern University, Chicago, IL 60611

DISCLOSURES: The authors report no conflicts of interest concerning this paper.

ACKNOWLEDGMENT: This work was supported by the Northwestern University Cancer Biostatistics Core and a Cancer Center Support Grant (NCI CA060553), the Jeff Hugo Foundation for Osteosarcoma Research, and the Brett Armin Sarcoma Foundation.

CORRESPONDING AUTHOR:  Mark A Agulnik, MD, mark.agulnik@nm.org

Abstract

Background: Clinical trials remain a cornerstone in the development of new cancer therapies. Patients diagnosed with bone and soft tissue sarcoma typically have comparatively low rates of trial participation, which may contribute to lack of progress. This cross-sectional survey study was designed to characterize patient attitudes, knowledge, perceived ability (ie, self-efficacy), receptivity, and willingness to participate in trials. As well, we explored perceptions related to tumor molecular profiling (TMP).

Methods: Patients with sarcoma who were evaluated at Northwestern Medicine (NM) between 2012 and 2017 were identified through the Enterprise Data Warehouse (NMEDW). A link to an online self-administered survey was emailed to patients. Data were analyzed using Spearman correlations and the Mann-Whitney test.

Results: Surveys were e-mailed to 750 patients, of which 20 emails bounced back and 309 were opened; 283 patients completed at least a portion of the survey and this population was used in this analysis (37.7% of total and 91.6% of opened). Of the responding patients, median age was 56 years, 59.4% were female, and 26.8% reported metastatic disease. Greater knowledge of trials correlated with increased positive attitudes toward trial participation (r=0.5; P<0.001) and positive attitudes correlated with greater trial perceived ability (r=0.4; P<0.02). Patients with metastatic disease had more positive attitudes compared with patients with non-metastatic disease (P=0.03). Trial enrollment was associated with greater knowledge (P=0.002) and positive attitudes (P=0.001). Among patients who reported knowledge of TMP (n=46), 65% credit TMP with a >50% chance of isolating a targetable result. Of patients who had TMP performed (n=18), important considerations included wanting to live as long as possible and helping future cancer patients, but not wanting to be part of research.

Conclusions: Increasing awareness, knowledge, and attitudes towards trials among patients with sarcoma may lead to increased trial enrollment and greater progress in cancer treatment. Patient-focused interventions and research-site optimization are critical to maximizing accrual rates and biomarker-driven therapeutics. Lessons from a sarcoma patient population can be used to optimize trial enrollment in an era of increasingly heterogeneous cancer populations.

Knowledge, attitudes, and perceived ability

A statistically significant correlation was observed between greater knowledge of trials and more positive attitudes towards trials (P<0.001; r=0.5, FIGURE 2A). In relating patient attitudes with perceived ability, again a significant correlation was seen (P<0.001; r=0.4, FIGURE 2B). In contrast, knowledge had a weak correlation with perceived ability (P=0.024; r=0.2, FIGURE 2C). There was no difference regarding patient knowledge, attitudes, or perceived ability by age, gender, race, or income.

Knowledge, attitudes, perceived ability, and clinical trial enrollment

Thirty patients reported clinical trial experience (either previously or currently enrolled in trials) and 160 patients were never enrolled. Of the 30 patients with trial experience, 7 reported being currently enrolled, while 23 reported previous enrollment. Of these patients, 16 had metastatic disease, while 12 had non-metastatic disease, and 2 were unsure whether or not they had metastatic disease.

Patients with previous clinical trial exposure (currently or previously enrolled in clinical trials) demonstrated significantly greater trial knowledge, with a mean knowledge score of 9.3 (CI 8.5-10.0) compared with 7.7 (CI 7.3-8.1) among patients without trial exposure (P=0.002; FIGURE 3A). Similarly, patients with trial experience also had statistically significant more positive attitudes towards trials as compared with patients with no trial experience, with a mean attitude score of 3.8 (CI 3.6-4.0) and 3.5 (CI 3.4-3.6), respectively (P=0.001; FIGURE 3B). While numerically patients with trial experience have greater perceived ability compared with patients with no trial experience, with a mean score of 4.4 (CI 4.2-4.6) and 4.2 (CI 4.1-4.3), respectively, this difference did not reach statistical significance (FIGURE 3C).

Knowledge, attitudes, perceived ability, and disease stage

An analysis was performed comparing patients with metastatic vs non-metastatic disease. It was observed that patients with metastatic disease had similar knowledge of trials compared with non-metastatic patients, with a mean knowledge score of 8.4 (CI 7.7- 9.1) and 7.9 (CI 7.5-8.4), respectively, (P=0.3; FIGURE 4A). In contrast, patients with metastatic disease had more positive attitudes compared with non-metastatic patients, with a mean score of 3.7 (CI 3.5-3.8) and 3.5 (CI 3.4-3.6), respectively, which was statistically significant (P=0.03; FIGURE 4B). There was no difference in perceived ability in metastatic vs non-metastatic patients (FIGURE 4C).

Thoughts about molecular profiling

Of the total number of patients, 46 patients had heard of molecular profiling and were presented with questions regarding their thoughts (TABLE 3). Approximately two-thirds (65.2%) thought there would be a 50% or greater likelihood of finding a targetable result in their tumor molecular profile. A majority (71.7%) of patients thought that a new experimental therapy chosen based on a patient’s tumor molecular profile would have at least a 50% chance of controlling the cancer. Somewhat less than a third (30.4%) of patients thought that total cure is the maximal benefit a patient could experience as a result of a treatment on a clinical trial using a drug chosen based on molecular tests. About half (52.2%) of patients agreed with the statement, “I am concerned about the cost of the test to molecularly profile my cancer.”

Considerations to undergo molecular profiling

Eighteen patients had undergone molecular profiling of their tumor. These patients were posed the question, “To what extent did you consider the following issues or concerns at the time you decided to get molecular testing of your cancer?” (TABLE 4). A majority (83.3%) of patients stated that wanting to live as long as possible was important, and 72.2% of patients stated that quality of life was important. A majority (83.3%) of patients stated that hope for a cure was an extremely or quite a bit important consideration. Helping future cancer patients was extremely or quite a bit important for 77.8% of patients, while wanting to be a part of research was not at all or of little importance in 50.0% of patients.

Clinical trials at NM

Twenty-four clinical trials were available at NM between the years 2012 and 2017 for patients with bone and soft tissue sarcoma. Of these trials, 3 of 24 were for non-metastatic patients, while the remaining 21 were open only to metastatic patients. The median number of patients screened per trial was 11 (range 0-66) and the median number of patients accrued per trial was 9 (range 0-58). Of the 24 trials, 17 were not subtype specific (13 included soft tissue sarcoma alone while 4 included both bone and soft tissue sarcoma). The remaining 7 trials were sarcoma subtype specific (eg, angiosarcoma, liposarcoma, etc). Trials available at NM during this period are included in TABLE 5. There were 318 patients screened and 262 patients accrued to sarcoma trials over this time period, with a screen failure rate of 17.6% overall.

Discussion

Our study sought to describe perceptions of clinical trial enrollment among patients with bone and soft tissue sarcoma in order to elucidate and overcome barriers to enrollment, which to the best of our knowledge had not been previously described. Using previously validated patient- reported outcomes in the literature,6 our data reveal a correlation between knowledge of trials and more positive attitudes towards trials. This underscores the importance of awareness and educational strategies in this cancer population as a whole. Interventions should focus on patient perceptions that contribute to lack of participation, such as fear of side effects, loss of control (eg, idea of placebo or randomization), logistical challenges (eg, additional time or convenient location), and cost.3,5,7,16,17 For example, patients concerned about randomization should be educated on equipoise and other ethical considerations in trial design.5 Previous research has suggested that a multimedia psychoeducational intervention was effective in improving attitudes toward trials.6 Educating patients on the essential role of trials in oncology care, as demonstrated by the vast number of new drug approvals in recent years, is an essential strategy to improve attitudes, and subsequently leads to higher patient accrual rates. 

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