Can clinical trials in renal cell carcinoma (RCC) be more inclusive of patient populations? Do we know what matters most to kidney cancer patients in treatment selection and follow-up? Are oncologists primarily responsible for patient education in community-based care of RCC—or is it someone else? How does the patient experience differ from one country to another? Investigators and advocacy groups are in hot pursuit of answers to these questions.
Exclusion criteria: Too exclusive?
“A significant proportion of renal cell carcinoma studies utilize overly restrictive eligibility criteria,” researchers reported during the ASCO Genitourinary Cancers Symposium in February and the International Kidney Cancer Symposium North America last November.1,2 The investigators reviewed exclusion criteria from 112 RCC trials of advanced or metastatic RCC treatment with start dates from June 30, 2012 to June 30, 2022. The exclusion criteria used most frequently were a history of HIV infection or AIDS (excluded in 74.1% of trials), known acute chronic hepatitis B or C infection (excluded in 53.6% of trials), symptomatic brain metastasis or a history of it (excluded in 33% of trials), and concurrent malignancies (excluded in 8% of trials).
“Appropriate broadening of criteria to incorporate patient populations mirroring a real-world setting will provide more useful data going forward,” the authors concluded. ASCO and the Friends of Cancer Research have made it a joint priority to eliminate overly restrictive exclusion criteria in clinical trials. The goals are to strengthen patient accrual in the studies, expand access to investigational treatments, and improve the generalizability of trial results.3
Case in point: the outcomes of patients with brain metastases of RCC are not well known because these patients are typically excluded from clinical trials. To address this gap, investigators from the United States, Canada, Europe, Japan, and Australia analyzed data from the International metastatic RCC Database Consortium (IMDC) for 775 patients who had brain metastases of RCC at the time they began first-line therapy.4
The cohort included patients receiving immuno-oncology-based combination therapy (IO/IO or IO/VEGF) or anti-VEGF monotherapy (sunitinib or pazopanib). Patients receiving IO-based combination therapy “may have longer overall survival than those receiving anti-VEGF monotherapy,” the researchers concluded. Also associated with longer overall survival were brain-directed local therapies, including neurosurgery and stereotactic radiosurgery. The group presented its findings during the general session of the ASCO Genitourinary Cancers Symposium.
The quest for more complete representation of patient populations in clinical trials will continue. A recent review of exclusion rates in randomized controlled trials of treatments for physical conditions cautioned that “exclusion of older people and people with co-morbidity and co-prescribing is increasingly untenable given population aging and increasing multimorbidity.”5
What matters most to patients
Another recent study suggests that treatment discussions with patients should focus not only on safety and efficacy but on other attributes as well, such as the convenience of treatment and its impact on quality of life. A survey of 299 patients with advanced or metastatic RCC found that seven attributes were statistically significant for influencing the choice of treatment: overall survival, progression-free survival, objective response rate, duration of response, risk of adverse events, quality of life changes, and treatment administration.6
Increasing survival time was the most important among the efficacy attributes, followed by objective response rate, progression-free survival, and duration of response. The next priority was reducing the risk of serious adverse events. The researchers also found that “patients with advanced RCC highly value less burdensome treatment regimens and improved quality of life, in addition to improvement in survival. This highlights the need for a broader context beyond safety and efficacy when discussing treatment options.” The study, presented at ASCO Genitourinary Cancers Symposium 2023, was supported by Bristol Myers Squibb.
A survey developed by the Kidney Cancer Research Alliance sheds light on patients’ perceptions of the benefits and risks of adjuvant therapy for high-risk, localized RCC.7 Of 113 patients offered adjuvant therapy, nearly half (49%) believed it would reduce their risk of recurrence by more than 30%, and 25% believed it would reduce their risk by more than 50%. Patients with stage 3 disease assessed their own risk of recurrence at 47% even though their doctors, on average, estimated the recurrence risk at 37%.
“The findings highlight the importance of effective communication between patients and providers regarding the risks and benefits of adjuvant therapy to promote an informed and shared decision,” the authors concluded.
Patient education in RCC: Whose responsibility?
In community-based care of RCC, the primary patient educator could be anyone on the treatment team, according to a survey conducted by the Association of Community Cancer Centers. Of 104 respondents, from local cancer centers or physician offices, 23% said the oncologist was responsible for comprehensive patient education. Other programs relied upon the infusion nurse (22%), clinic nurse (20%), advanced practice provider (18%), or pharmacist (16%).8
Nearly half (45%) of respondents said they schedule regimen-specific patient education as a separate visit, while 37% provide education on the first day of treatment. A sizeable minority (39%) do not frequently use risk scores to guide treatment selection for newly diagnosed patients. The study, supported by Pfizer, is part of an ongoing effort to evaluate real-world practice patterns for patients with RCC, including selection of treatment and monitoring for adverse events.
Real-world (worldwide) perspectives on RCC
Little is known about country-to-country variation in the care of RCC, from best clinical practices to patient experiences. To help fill that gap, the International Kidney Cancer Coalition conducted its third biennial Global Patient Survey on the diagnosis, treatment, and overall disease burden of RCC.9,10 The survey, developed with the input of national and international cancer associations (EAU, ESMO, ASCO, NCCN) gathered information on six key dimensions of care: patient education, experience and awareness, access to care and clinical trials, best practices, quality of life, and unmet psychosocial needs.
The survey results, based on 2,213 responses from 39 countries, point to a need for more genetic testing and counseling of patients at hereditary risk of RCC and greater understanding of the psychosocial effects of disease. The impact of the cancer diagnosis on patients’ emotional wellbeing included persistent anxiety (20%), sadness or depression (11%), and fear of recurrence (28%). More than a third of patients surveyed were offered the opportunity to take part in a clinical trial; 70% accepted and two-thirds (65%) said they were very satisfied or satisfied with the experience. The International Kidney Cancer Coalition will use the results “to ensure that patients’ voices are heard.”9,10
IO=immuno-oncology; VEGF=vascular endothelial growth factor.
- Prajapati SR, Feng MI, Castro DV, et al. Evaluation of eligibility criteria in contemporary renal cell carcinoma based on ASCO-FCR recommendations. Abstract 612 presented at: ASCO Genitourinary Cancers Symposium; February 16-18, 2023; San Francisco, CA.
- Castro DV, Chan EH, Feng MI, et al. Critical assessment of eligibility criteria in contemporary renal cell carcinoma (RCC) trials evaluating systemic therapy. Presented at International Kidney Cancer Symposium North America; November 4-5, 2022.
- Kim ES, Uldrick TS, Schenkel C, et al. Continuing to broaden eligibility criteria to make clinical trials more representative and inclusive: ASCO-Friends of Cancer Research Joint Research Statement. Clin Canc Res. 2021;27(9):2394-2399.
- Takemura K, Lemelin A, Ernst MS, et al. Outcomes of patients with brain metastases from renal cell carcinoma treated with first-line therapies: results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Abstract 600 presented at: ASCO Genitourinary Cancers Symposium; February 16-18, 2023; San Francisco, CA.
- He J, Morales DR, Guthrie B. Exclusion rates in randomized controlled trials of treatments for physical conditions: a systematic review. Trials. 2020;21:228.
- Ornstein MC, Rosenblatt L, Ejzykowicz F, et al. Assessing treatment preferences among patients with advanced/metastatic renal cell carcinoma in the United States: a discrete choice experiment. Abstract 630 presented at: ASCO Genitourinary Cancers Symposium; February 16-18, 2023; San Francisco, CA.
- Battle D, Msaouel P, Pal SM, et al. Patient perceptions of benefits and risks of adjuvant therapy in renal cell carcinoma. Abstract 663 presented at: ASCO Genitourinary Cancers Symposium; February 16-18, 2023; San Francisco, CA.
- Boehmer L, Wood LS, Mohs J, et al. An evaluation of current practice patterns for patients with renal cell carcinoma. Abstract 655 presented at: ASCO Genitourinary Cancers Symposium; February 16-18, 2023; San Francisco, CA.
- Giles RH, Maskens D, Marconi L, et al. 2022 Global patient survey: reported experience of diagnosis, management, and burden of renal cell carcinoma. Abstract 653 presented at: ASCO Genitourinary Cancers Symposium; February 16-18, 2023; San Francisco, CA. https://ikcc.org/wp-content/uploads/2023/02/ASCO-GU23-IKCC-GPS-Poster-final.pdf. Accessed March 26, 2023.
- International Kidney Cancer Coalition. Summary of Kidney Cancer Highlights from ASCO GU 2023. https://ikcc.org/summary-of-kidney-cancer-highlights-from-asco-gu-2023/. Accessed March 26, 2023.