The authors wanted to evaluate the real-life utilization of these drugs and various treatment sequencing to achieve better outcomes, with respect to efficacy and safety of all the newly approved treatments.
In the presented study -PAZOREAL (Pazopanib and Everolimus in a Real-world Setting), the primary objective was to evaluate the effectiveness of pazopanib as a first-line therapy, followed by nivolumab as a second-line therapy and everolimus (also in the approved combination with lenvatinib) as a second-line and third-line therapy of patients with mRCC in the real-life setting. The primary outcome was measurement of the duration of response (time on drug as primary variable).
This was a prospective, multicenter, noninterventional study evaluating the effectiveness, tolerability, safety, and quality of life (QOL) in patients with advanced or metastatic RCC treated with first-line pazopanib followed by nivolumab or everolimus in second-line therapy, or everolimus (also in the approved combination with lenvatinib) in the third-line therapy after nivolumab.
In order to be eligible for the trial, adult patients had to be with advanced/metastatic RCC and have a life expectancy of at least 6 months, and having started treatment with first-line pazopanib or third-line everolimus for a duration maximum of 8 weeks prior to informed consent. All enrolled patients were assigned to either Cohort 1: First-line treatment with pazopanib, or to cohort 2: Third-line treatment with everolimus after second-line nivolumab.
Between 2015 and 2017, 421 patients were accrued for the study, and the authors presented only the results of the second interim analysis for a total of 385 patients treated with 1st line pazopanib (cohort 1). Out of these 385 patients 4 and 75 patients were treated with 2nd line everolimus and nivolumab, respectively. Subsequently, 24 patients entered the follow-up observation and 2 patients received everolimus as the third-line treatment following nivolumab (Figure 1).
End of treatment with 1st line pazopanib was demonstrated in 212 patients (Figure 2 demonstrates the reasons for end of pazopanib treatment).
Figure 2 – Reasons for end of treatment with pazopanibOverall survival data is shown in Figure 3 and 1st line treatment related adverse events are demonstrated in Figure 4.
Figure 3 – Overall survival data
Figure 4 – 1st line treatment related adverse eventsDeath was documented for 63 patients during the first-line pazopanib treatment, with the main causes being progression (n = 34) and serious adverse events (n = 17). In total, 80 patients died in cohort 1.
The most common reasons for dose reduction for pazopanib were physician’s decision
(33.5%), and the most common reason for dose interruption for pazopanib was toxicity (20.3%). Serious adverse events occurred in 15.1% of patients, but no drug relation was suspected. For nivolumab, the most common reasons for end of treatment were serious adverse events (14.7%), and physician’s decision (9.3%). The median score of the Visual Analogue Scale (0-100) was 70.0 at baseline and remained stable during the first 9 months of 1st line pazopanib treatment (Figure 5 demonstrates all quality of life assessments).
Figure 5 – Quality of life assessmentsThe authors concluded that this study demonstrated acceptable effectiveness, safety, and tolerability of pazopanib in the real-world setting. At the time of the second interim analysis, most patients were still under first- line treatment. Thus, patient numbers for the second line and later lines were not large enough to be analyzed. The OS data are not yet mature, and the OS analysis is still ongoing in this important trial.
Presented by: Martin Boegemann, University of Muenster Medical Center, Münster, Germany
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter:@GoldbergHanan at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA