A randomised, phase II study of nintedanib or sunitinib in previously untreated patients with advanced renal cell cancer: 3-year results

Abstract

Background: This exploratory study evaluated the safety/efficacy of nintedanib or sunitinib as first-line therapy in patients with advanced renal cell carcinoma (RCC).

Methods: Ninety-six patients were randomised (2:1) to either nintedanib (200 mg twice daily) or sunitinib (50 mg kg(-1) once daily (4 weeks on treatment; 2 weeks off)). Primary endpoint was progression-free survival (PFS) at 9 months. P-values reported are descriptive only; the study was not powered for such comparisons.

Results: Progression-free survival at 9 months was comparable between nintedanib and sunitinib (43.1% vs 45.2%, respectively; P=0.85). Median PFS was 8.4 months in each group (hazard ratio (HR), 1.12; 95% confidence interval (CI): 0.70-1.80; P=0.64). Median overall survival was 20.4 and 21.2 months for nintedanib and sunitinib, respectively (HR, 0.92; 95% CI: 0.54-1.56; P=0.76). Overall incidence of any grade adverse events (AEs) was comparable (90.6% vs 93.8%); AEs grade ⩾ 3 were lower with nintedanib than sunitinib (48.4% vs 59.4%). Nintedanib was associated with lower incidences of some AEs typical of antiangiogenic tyrosine kinase inhibitors (TKIs): hypertension, hypothyroidism, hand-foot syndrome, cardiac disorders and haematological abnormalities.

Conclusions: In patients with advanced RCC, nintedanib has promising efficacy and similar tolerability to sunitinib, and a manageable safety profile with fewer TKI-associated AEs.

Figure 1

Patient enrolment and study flow (CONSORT diagram). ^aOne patient was randomised in error and had no measurable disease; one patient withdrew consent prior to receiving their first dose of study treatment; and one patient who was admitted with pleural effusion was not considered well enough to continue, and was withdrawn before receiving their first dose of study treatment. ^bOne patient discontinued treatment with a left ventricular fraction level below threshold, one patient discontinued with signs of clinical progression that were not confirmed, and a further one patient discontinued with evidence of increasing bone destruction of the right maxilla but no other sites of progression.

Figure 2

Kaplan–Meier plot for progression-free survival by investigator assessment. Patients without documented progression were censored at the date of their last tumour assessment. Crosses denote censoring events. At the cut-off date for 3-year analysis, 53 patients (82.8%) in the nintedanib group and 27 (84.4%) in the sunitinib group had progressed or died. Hazard ratio and confidence intervals for the overall treatment groups were obtained from Cox proportional hazards models stratified by Motzer risk score and previous surgery. Abbreviations: CI=confidence interval; HR=hazard ratio.

Figure 3

Kaplan–Meier plot for overall survival. Patients without documented death at the time of analysis were censored on the date that they were last known to have been alive. Crosses denote censoring events. At the cut-off date for 3-year analysis, 42 patients (65.6%) in the nintedanib group and 21 (65.6%) in the sunitinib group had died. Hazard ratio and confidence intervals for the overall treatment groups were obtained from Cox proportional hazards models stratified by Motzer risk score and previous surgery. Abbreviations: CI=confidence interval; HR=hazard ratio; NE=not evaluable.