The median overall survival in renal cell carcinoma patients was similar, regardless of whether or not patients received a break from treatment.
Patients receiving tyrosine kinase inhibitor (TKI) treatment for renal cell carcinoma can likely take a treatment break without increasing their risk of mortality, according to data from the phase 2/3 STAR trial published in the Lancet Oncology.1
The findings showed that although non-inferiority could not be determined following planned treatment cessation vs conventional continuation with a first-line TKI, patients with advanced clear cell renal cell carcinoma did not experience a clinically meaningful decrease in survival outcomes.
The median overall survival (OS) was 28 months (95% CI, 24-32) in the conventional strategy group vs 27 months (95% CI, 23-31) for the drug-free interval group in the per protocol population. For the intent-to-treat (ITT) population, the median OS was 28 months (95% CI, 24-32) in the conventional continuation group vs 27 months (95% CI, 23-33) in the drug-free interval group.
Investigators also noted that there was noninferiority with regard to quality-adjusted life years (QALYs) in the ITT group (marginal effect difference 0.06; 95% CI, –0.11 to 0.23) and the per-protocol population (marginal effect difference 0.04; 95% CI, –0.14 to 0.21).
A total of 920 patients were randomly assigned to either the conventional continuation group (n = 461) or the drug-free interval group (n = 459). The median follow-up for both groups was 58 months. Patients received 50 mg of oral sunitinib (Sutent) a day or 800 mg of oral pazopanib (Votrient) a day.
The ITT population included 919 patients and the per-protocol group included 871. Overall, 73% of patients were male and 96% were White.
Treatment discontinuation was necessary in 47% of patients before beginning randomization at week 24. Reasons for discontinuation included radiological disease progression (58% vs 54%), and toxicity (31% vs 32%) in the continuation and drug-free groups, respectively.
Patients received a median of 4 treatment cycles; before week 24, the median number of treatment cycles was identical between the 2 groups. A dose reduction was necessary in 45% of patients in the conventional group vs 46% in the drug-free interval group.
A total of 54% of patients in the drug-free interval group continued the trial past 24 weeks, of whom 85% started their first treatment break via protocol at week 24. Among the remaining patients (n = 38), 15 did not take a break and continued treatment at week 24 due to error, then withdrew from treatment or had radiological progression.
Additionally, 12 patients took their first break at week 36, 6 patients at week 48, 2 patients at week 60, and 3 at other time points. In the conventional continuation group, 52% continued treatment after week 24.
The median number of breaks was 1 and the maximum number of breaks was 9. The median length of all treatment breaks was 87 days. Three percent of patients in the drug-free interval group withdrew to receive continuous treatment.
A total of 74% of patients in the per-protocol group died.
Investigators also reported a hazard ratio of 0.75 (95% CI, 0.66-0.86; P <.0001) for time to strategy failure, 0.77 (95% CI, 0.67-0.89; P = .00037) for summative progression-free interval, 0.75 (95% CI, 0.65-0.86; P <.0001) for time to treatment failure, and 1.37 (95% CI, 1.19-1.57; P <.0001) for progression-free survival.
The most common grade 3 or higher adverse effects (AEs) included hypertension (26% vs 29%), hepatotoxicity (11% vs 11%), and fatigue (8% vs 15%) in the conventional continuation strategy group vs the drug-free interval group.
The most common serious AEs included gastrointestinal disorders (34% vs 16%); infections and infestations (8% vs 13%); and respiratory, thoracic, and mediastinal disorders (8% vs 9%) in the conventional continuation group vs the drug-free interval group, respectively.
Death due to serious AEs occurred in 12 patients and included 3 patients from the conventional continuation group and 9 from the drug-free group. Causes of death included vascular (n = 3), cardiac (n = 3), hepatobiliary (n = 3), gastrointestinal (n = 1), or nervous system (n = 1) disorders, and from infections and infestations (n = 1).
A post-hoc analysis looked at a clinical response in patients who had not progressed at 24 weeks; investigators noted that the depth of response was similar between the conventional continuation and drug-free interval groups.
Initial treatment response was observed in 245 patients in the conventional continuation group with less than 1% having a complete response (CR), 26% having a partial response (PR), and 74% having stable disease. Among 250 patients in the drug-free interval group who responded to initial treatment, the CR rate was 1%, PR rate was 23%, and stable disease rate was 76%.
Reference
1. Brown JE, Royle KL, Gregory W, et al. Temporary treatment cessation versus continuation of first-line tyrosine kinase inhibitor in patients with advanced clear cell renal cell carcinoma (STAR): an open-label, non-inferiority, randomised, controlled, phase 2/3 trial. Lancet Oncol. 2023;24(3):123-227. doi:10.1016/S1470-2045(22)00793-8
Dosing commences in phase 1/2 trial of AB-2100 in ccRCC
May 15th 2024The dose escalation/dose expansion study is evaluating the safety and efficacy of AB-2100 in patients with ccRCC who either came back or did not improve following prior treatment with a checkpoint inhibitor and a VEGF inhibitor.
Grant awarded to aid development of allogeneic CAR T treatment for RCC
April 29th 2024“This clinical study has the potential to demonstrate the value of Chimeric Antigen Receptor (CAR) T cell therapy in solid cancers such as kidney cancer with a high unmet medical need,” said Abla Creasey, PhD.
Updated data show survival benefit with adjuvant pembrolizumab in ccRCC
April 19th 2024“This is the first study to show a statistically significant and clinically meaningful survival improvement with any adjuvant therapy in kidney cancer, and this further supports adjuvant pembrolizumab as a standard of care after surgery in this disease setting,” says Toni K. Choueiri, MD.
Toripalimab plus axitinib approved in China for renal cell carcinoma
April 11th 2024The approval is based on findings from the phase 3 RENOTORCH trial, which showed that toripalimab plus axitinib prolonged progression-free survival and improved the objective response rate in patients with advanced RCC compared with sunitinib.