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TKI drug-free interval strategy not detrimental to conventional continuation strategy in RCC

Presented By
Prof. Janet Brown, University of Sheffield, UK
ESMO 2021
Phase 2, STAR
First results from the phase 2/3 STAR trial showed that a drug-free interval strategy in tyrosine kinase inhibitor (TKI)-therapy in patients with advanced/metastatic renal cell carcinoma (RCC) is not detrimental to overall survival (OS) and quality of life compared with conventional continuation strategy, and has a significant cost saving effect.

TKI therapy is an important backbone in the management of locally advanced or metastatic RCC, with significant survival advantage. However, TKI therapy is associated with significant toxicities which often lead to dose reduction and/or discontinuation of treatment. In addition, TKI therapy comes with high costs. The multicentre, randomised, phase 2/3 STAR trial (EudraCT 2011-001098-16) was designed to determine if a TKI drug-free interval strategy (DFIS) was non-inferior to a conventional continuation strategy (CCS) in the first-line treatment of advanced RCC. Outcomes were overall survival (OS) and Quality Adjusted Life Years (QALYs). Both co-primary endpoints (OS and QALYs) had to demonstrate pre-defined non-inferiority (≤7.5% for OS; ≤10% for QALYs) in intention-to-treat and per-protocol analyses for non-inferiority to be concluded. Prof. Janet Brown (University of Sheffield, UK) presented the first results of the STAR trial [1].

A total of 920 patients with newly diagnosed metastatic RCC who started treatment with sunitinib or pazopanib were 1:1 randomised to DFIS or CCS. Overall, 488 (53.0%) patients (CCS, n=240; DFIS, n=248) continued on trial post-week 24. Intention-to-treat and per-protocol analyses included 461 versus 458 patients and 453 versus 418 patients, respectively.

After 24 weeks of treatment, DFIS patients took a treatment break until disease progression, with additional breaks dependent on disease response and patient/clinician choice. Trial strategy continued until intolerance, progression on treatment, or death. At least one treatment break was mandated, with a median treatment break length of 87 days; 27% of patients had 3 or more treatment breaks.

For OS, in the intention-to-treat population, HR was 0.97 (95% CI 0.83–1.12), whereas in the per-protocol population, HR was 0.94 (95% CI 0.80–1.09). With a non-inferiority margin of 95% CI ≥0.812, this meant DFIS in the per-protocol population could not be regarded as non-inferior to CCS. However, consistent non-inferiority in both populations was demonstrated for QALYs. At 2 years, DFIS was associated with cost savings (£6,954 per-participant).

“Although OS just fell short of predefined non-inferiority, probably due to fewer than expected events, non-inferiority of DFIS for QALYs was demonstrated. DFIS also appeared to be highly cost-effective compared to CCS. In addition, DFIS was seen to be acceptable to patients and clinicians,” summarised Prof. Brown.

  1. Brown JE, et al. STAR: A randomised multi-stage phase II/III trial of standard first-line therapy (sunitinib or pazopanib) comparing temporary cessation with allowing continuation, in the treatment of locally advanced and/or metastatic renal Cancer (RCC). Abstract LBA28, ESMO Congress 2021, 16–21 September.


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