Patients with metastatic clear cell renal cell carcinoma (mRCC) and Performance Status 2 have historically been excluded from clinical trials, resulting in a lack of evidence on which to base treatment decisions. Pazo2 was a phase II, multicentre, single arm trial that aimed to determine tolerability and efficacy of pazopanib in mRCC patients with ECOG PS2. The Bryant and Day design allows for joint evaluation of two primary outcomes. Tolerability was defined as the proportion of patients at 6 months who were free from drug-related grade 3-4 toxicities resulting in SAE reporting or drug discontinuation > =3 weeks. Efficacy was defined as the proportion of patients progression free (RECIST 1.1) and alive at 6 months. Secondary endpoints included response, drug safety, progression free survival (PFS) and overall survival (OS).
Patients with mRCC and ECOG PS 2 without prior systemic treatment were registered. Undesirable tolerability was set at 40%, with 60% being desirable. Undesirable efficacy was set at 25%, with 44% being desirable (power 85% α 5%). Treatment comprised pazopanib 800mg PO once daily (OD). Dose modifications using 600mg PO, OD and 400mg PO, OD were permitted. Treatment continued until progression or unacceptable toxicity.
A total of 75 patients were registered into the trial from 26 UK sites between 2013-2016. All patients were ECOG PS 2; median age 68 years (IQR 64, 76), 72% were male, HENG poor prognosis 59% and intermediate prognosis 41%. 47 patients met the tolerability criteria (vs 34 required). Further analysis showed that 18 (24%) patients stopped treatment due to toxicity within the same period. 23 patients were required to be progression free and alive at 6 months with 38 being observed. Kaplan Meier 6 month PFS was 66% (95% CI, 54, 76), with a median PFS of 9 months (95% CI 7.6, 13.5). Overall survival data is not yet mature.
Our results suggest that treatment with pazopanib is tolerable and shows similar efficacy in ECOG PS 2 patients as compared to previously reported data with ECOG PS 0/1. This suggests that excluding patients from trials based solely on their performance status may not appropriate.
Clinical trial identification
EudraCT: 2011-001211-31, ISRCTN: 38957238, Cancer Research UK Endorsement: C11225/A12402.
Legal entity responsible for the study
The University of Birmingham.
E. Porfiri: Grants: Novartis, during the conduct of the study; Personal (speaker and advisory board) fees: Novartis, Pfizer, BMS, Ipsen, outside the submitted work. K. Fife: Non-financial support: BMS; Personal fees: BMS, Ipsen, Pfizer, Roche, Esai, Novartis, outside the submitted work. C. McDonald-Smith: Personal fees: Pfizer, BMS, outside the submitted work. N.S. Vasudev: Non-financial support: Ipsen; Grants and non-financial support: Bristol Myers Squibb, outside the submitted work. All other authors have declared no conflicts of interest.