ASCO GU 2021: Real-World Treatment Patterns and Sequencing for mRCC: Results from the Flatiron Database

(UroToday.com) Renal cell carcinoma (RCC) accounts for ~80%‒90% of all kidney cancers worldwide, with metastatic RCC (mRCC) portending a poor prognosis with a historical 5-year relative survival of 13%. The mRCC treatment landscape is rapidly changing with the approval of new therapies, which has recently been broadened by the FDA approvals of immunotherapy monotherapy in November 2015, dual immunotherapy in April 2018, and more recently immunotherapy-TKI combinations in April 2019. Despite the expanding number of available immunotherapy-based mRCC treatment options, data on the impact of immunotherapy approval on real-world treatment patterns and sequencing are limited. At the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Dr. Saby George and colleagues presented results of their study investigating the characteristics, treatment patterns, and sequencing for mRCC patients in the real-world setting (December 2015‒May 2020) and in a subgroup analysis of post-dual immunotherapy approval in the United States (April 2018‒May 2020).


For this retrospective study, adults diagnosed with mRCC between December 2015 and May 2020 were selected from the Flatiron electronic medical record database. The Flatiron Health Database is a longitudinal database comprising deidentified patient-level structured and unstructured data curated via technology-enabled abstraction. The majority of the patients in the database originate from US community oncology settings and relative US community/academic proportions may vary depending on the study cohort. This study cohort was required to have ≥ 1 month of medical data from the initial mRCC diagnosis date (index date), and the start of first-line therapy was the first episode of an eligible therapy given after or up to 14 days before the diagnosis and after the patient’s start of structured activity. When a gap of >120 days occurred during drug episodes, the line of therapy number was advanced.  Descriptive statistics were used to analyze baseline patient demographic and clinical characteristics, treatment patterns, and treatment sequencing in the overall cohort and in a subgroup of patients initiating first-line therapy during or after April 2018 (the month after FDA approval of combination immunotherapy) through to May 31, 2020.

There were 3,524 patients with mRCC (overall cohort, December 2015–May 2020), most who were male (68.5%), White (66.5%), and had clear cell histology (68.2%). The median age at metastatic diagnosis was 68 years (range, 23–85) and the median follow-up from index date was 10.8 months (range: 0.3-54.6). Based on IMDC risk score, 75.8% of patients were categorized as intermediate/poor risk and 23.2% as favorable risk. Systemic therapy for RCC was initiated in 79.1% (n = 2,788) of patients, and the most common treatments for first-line therapy were TKI monotherapy (56.4%), combination immunotherapy (19.1%), combination immunotherapy-TKI (9.5%), immunotherapy monotherapy (6.9%), and others (8.1%). Among patients who initiated first-line treatment post-April 2018 (n = 1,395), the most common treatments for first-line therapy were combination immunotherapy (36.9%) and TKI monotherapy (32.7%):

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Second-line therapy was received by 1,303 patients. The most common sequences were pazopanib to nivolumab (60.8% of TKI monotherapy to immunotherapy monotherapy), pazopanib to cabozantinib (34.3% of TKI monotherapy to TKI monotherapy), and nivolumab plus ipilimumab to cabozantinib (73.2% of combination immunotherapy to TKI monotherapy). Among patients who received immunotherapy-based therapy in the first-line (n = 990), 11% were retreated with immunotherapy on any subsequent line. When stratified by clear cell and non-clear cell histology, similar treatment patterns and sequences were observed. Among patients who received second-line treatment after initiating first-line post-April 2018 (n = 4,86), TKI monotherapy followed by immunotherapy monotherapy, and combination immunotherapy followed by TKI monotherapy were the most prescribed sequences. The most common sequences were pazopanib to nivolumab (46.8% of TKI monotherapy to immunotherapy monotherapy), nivolumab plus ipilimumab to cabozantinib (74.5% of combination immunotherapy to TKI monotherapy), pazopanib to cabozantinib (35.3% of TKI monotherapy to TKI monotherapy), and cabozantinib to nivolumab plus ipilimumab (50.0% of TKI monotherapy to combination immunotherapy):

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Dr. George concluded this presentation of real-world utilization practices for the treatment of mRCC with the following take-home messages:
  • Following approval of immunotherapy-based therapies for first-line treatment, real-world treatment patterns for mRCC are evolving
  • Consistent with past treatment approvals and prescribing patterns, TKI monotherapy was broadly used as first-line therapy between December 2015 and June 2020 in this US community-based dataset
  • A new treatment pattern is emerging among patients initiating treatment for mRCC following approval of dual immunotherapy, as combination immunotherapy has become the most prescribed first-line therapy, while TKI monotherapy is beginning to show evidence of decline

Presented by: Saby George, MD, FACP, Medical Oncologist, Roswell Park Cancer Institute, Buffalo, NY

Co-Authors: Jillian Faccone, Stephen Huo, Ying Zhang, Brian Stwalley, Melissa Hamilton, Trong Kim Le, Flavia Ejzykowicz; Roswell Park Cancer Institute, Buffalo, NY; Bristol Myers Squibb, Princeton, NJ


Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021
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