Metastatic renal cell carcinoma: An ODYSSEY in the real world of patient care

By PRI Healthcare Solutions

The treatment of metastatic renal cell carcinoma (mRCC) is moving along in the fast lane of change. The therapeutic landscape “has changed dramatically over the past 7 years with the approvals of tyrosine kinase inhibitors (TKI) and immuno-oncology (IO) agents, alone or in combination,” researchers noted during the ASCO Genitourinary Cancers Symposium in San Francisco in mid-February. “However, multiple knowledge gaps remain. While active surveillance remains an option for selected patients, prospective evidence on selection of treatment and outcomes for patients is limited … there are also no routinely used predictive biomarkers in mRCC patient management.”1

The researchers, presenting at a Trials in Progress poster session at the ASCO Genitourinary Cancers Symposium, are taking part in an ambitious effort to gauge the impact of new drug approvals and other scientific advances in kidney cancer treatment “in routine real-world clinical practice in the United States.”1,2 The program has an ambitious name as well: ODYSSEY RCC, Outcomes Database to prospectivelY aSSEss the Changing therapY Landscape in Renal Cell Carcinoma.

ODYSSEY RCC, launched in April 2022 and expected to run through July 2026, is a prospective, observational cohort phase IV study of 800 patients (age 19 and older) with mRCC. The primary objective is to determine “distinct patterns of change in the quality of life and symptom burden” of patients undergoing treatment in community or academic settings. Primary outcome measures also include changes in patient-reported medication adherence.

“Addressing the evidence gap for how real-world patients symptomatically change with treatment combinations and sequences over time is a pressing unmet need,” the investigators noted in their poster presentation.1 Such longitudinal changes, they noted, are “poorly understood” outside the setting of an interventional clinical trial, and patient-reported outcomes “are rarely captured in a systematic manner.” The study will compare outcomes of different combination regimens, IO/IO and IO/TKI, as the comparator in most clinical trials is sunitinib.

Secondary outcomes include first-line and subsequent treatment selection, dosing, duration of treatment, time to next treatment, early discontinuation of one agent of a combination, concomitant use of glucocorticoids, work productivity and activity impairment, health care resource utilization, and overall survival.2

Data on patient-reported outcomes will be collected at baseline (prior to treatment), every 3 months for 2 years, and then every 6 months until the end of follow-up, with a minimum follow-up of 18 months and a maximum of 36 months. To minimize the burden of data collection on individual treatment sites, ODYSSEY will make use of the National Patient-Centered Clinical Research Network, “a network of networks” that curates information from multiple health systems. Study centers currently recruiting include the State University of Iowa, University of Kansas, Johns Hopkins University, Medical College of Wisconsin, University of Pittsburgh, University of Michigan, University of Texas Southwestern Medical Center, University of Utah, and Duke University.

The principal investigator for ODYSSEY is Daniel J. George, MD, a medical oncologist and co-leader of Duke Cancer Institute’s Center for Prostate and Urologic Cancers. Duke is sponsoring ODYSSEY in collaboration with Bristol-Myers Squibb, Exelixis, Merck Sharp & Dohme LLC, and Pfizer.

A first: ASCO Guidelines on mRCCIn the meantime, and for the first time, ASCO in June of 2022 published a set of comprehensive, evidence-based clinical practice guidelines for the management of metastatic clear-cell RCC. “In just over a decade,” the guideline Expert Panel noted, “this malignancy has gone from orphan disease status to mainstream, with multiple treatment options available, and the need for guidelines.”3

The guideline panel conducted a systematic analysis of 56 studies and reviews published in the literature between 2007 and March 2022, including 46 randomized trials. The guidelines address “six overarching clinical questions”:

The panel responded to these six questions with a total of 20 recommendations. The document also emphasizes that “continued work is needed to define predictive and prognostic biomarkers to further tailor treatments to tumors to increase efficacies while decreasing toxicities (physiologic, psychologic and financial).”3

The guidelines also recognize the need to fine-tune personalized treatment and set clear patient criteria for each recommended intervention. “Identifying those who have the most efficacious outcomes for each treatment can potentially improve survival, reduce patient cost, and increase medical institution effectiveness,” the guidelines state. Those, in fact, are some of the questions the ODYSSEY study is seeking to answer.

Apart from the clinical issues explored, the guidelines stress the importance of patient-clinician communication to keep abreast of changes as the treatment landscape morphs at a rapid clip. The two patient advocate representatives on the panel shared a few key suggestions:

In addition to the ASCO guidelines, a number of recent review articles have offered perspectives on navigating the shifting terrain of metastatic kidney cancer.4,5 Also on the horizon: efforts to provide guidance in the management of non-clear cell metastatic RCC,6 which is not covered in the 2022 ASCO guidelines.

A growing body of real-world evidenceMeanwhile, the edifice of real-world evidence in the management of mRCC continues to build, brick by brick and study by study. A paper presented at the International Kidney Cancer Symposium, North America last November reported a notable shift in first-line treatment for mRCC.7

The study included 1,538 patients (median age 67.1 years) who received first-line treatment for mRCC between January 1, 2018 and September 30, 2020. Data came from the US Oncology Network and clinics outside the network that use the iKnowMed electronic health record system.

First-line therapies helped guide second-line treatment. Most patients received a TKI second-line if they received IO-based treatment first-line, and vice versa.

The authors published a full report on their findings, including clinical outcomes, earlier this year in European Urology Open Science.8 They noted that “IO + IO and IO + TKI combination therapies have revolutionized management of mRCC.” The “substantial uptake” of IO-based therapies for first-line treatment suggests “rapid implementation of these new treatments by oncologists working in the community setting, which is reassuring for patients with this disease.”8

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