Real-world effectiveness of first- and second-line anti-angiogenesis therapy in RCC: analysis of a UK-based population
Creators: name: Waddell, Tom
name: Pillai, Manon
name: Armitage, Kate
name: Graham, Donna M
name: Moran, Michael
name: Dilleen, Maria
name: Holmes, Sinead
name: Śleszyńska-Dopiera, Ewa
name: Hawkins, Robert
Publisher: name: Taylor & Francis
Year: 2024
Subjects: Medicine
Pharmacology
Biotechnology
Cancer
Virology

description: <b>Aim:</b> Renal cell carcinoma (RCC) is the seventh commonest cancer in the UK, where first-line (1L) sunitinib and second-line (2L) axitinib are treatment options. <b>Methods:</b> Retrospective, non-interventional data from the Christie NHS Foundation Trust (Manchester, UK). The primary end point was median progression-free survival (mPFS). <b>Results:</b> For 1L sunitinib (n = 622) and 2L axitinib (n = 121), mPFS (95% CI) was 8.4 (7.6, 9.9) and 6.2 (4.9, 9.3) months, respectively. In 1L, Karnofsky performance status, lactate dehydrogenase (LDH), neutrophils, hemoglobin, time from diagnosis to treatment and age were predictors (<i>p</i> &lt; 0.05) of PFS. In 2L, LDH and platelets were predictors of PFS (<i>p</i> &lt; 0.05). <b>Conclusion:</b> Sunitinib and axitinib were effective treatments for RCC. PFS predictors varied between 1L and 2L; LDH was a predictor for both. <b>Clinical Trial Registration:</b>NCT04033991 (ClinicalTrials.gov). Renal cell carcinoma (RCC) is the seventh most common type of cancer in the UK. In the UK, axitinib plus avelumab, lenvatinib plus pembrolizumab and nivolumab plus ipilimumab are approved for reimbursement within the NHS. Other approved 1L treatment options include axitinib plus pembrolizumab and cabozantinib plus nivolumab. Previous RCC first-line (1L) mainstay, sunitinib may be a treatment option when ICIs are not appropriate, or single-agent therapy is preferred. Axitinib is recommended as a 2L treatment when not administered in 1L. This study aimed to understand the clinical outcomes of patients with advanced RCC treated with 1L sunitinib and second-line (2L) axitinib in a real-world, UK-based setting, utilizing data extracted from a clinical database held by the Christie NHS Foundation Trust (Manchester, UK). For 1L sunitinib (n = 622), median progression-free survival (PFS) and overall survival (OS) (95% CI) were 8.4 (7.6, 9.9) and 18.3 (15.8, 20.4) months, respectively. For 2L axitinib (n = 121), median PFS and OS (95% CI) were for 6.2 (4.9, 9.3) and 15.8 (12.0, 20.4) months, respectively. Karnofsky performance status, lactate dehydrogenase (LDH), neutrophils, hemoglobin, time from diagnosis to treatment initiation and age were significant (<i>p</i> &lt; 0.05) predictors of PFS for 1L sunitinib. For 2L axitinib, LDH and platelets were significant predictors for PFS. 59 patients received both 1L sunitinib and 2L axitinib.○ Of the 13 (22.0%) patients who were of favorable IMDC risk at 1L, four (30.8%) remained of favorable risk, eight (61.5%) progressed to intermediate risk and one (7.7%) progressed to poor risk when receiving 2L.○ Of the 28 (47.5%) patients who were of intermediate risk at 1L, 20 (71.4%) remained of intermediate risk, four (14.3%) progressed to poor risk, but four (14.3%) transitioned to favorable risk during 2L. Of the 13 (22.0%) patients who were of favorable IMDC risk at 1L, four (30.8%) remained of favorable risk, eight (61.5%) progressed to intermediate risk and one (7.7%) progressed to poor risk when receiving 2L. Of the 28 (47.5%) patients who were of intermediate risk at 1L, 20 (71.4%) remained of intermediate risk, four (14.3%) progressed to poor risk, but four (14.3%) transitioned to favorable risk during 2L. In a real-world UK setting, 1L sunitinib and 2L axitinib were effective treatments for RCC. Predictors of PFS varied between the 1L and 2L cohorts, with only LDH as a significant predictor for both lines of treatment. 1L sunitinib and 2L axitinib were effective when given in sequence.