Rare patients in routine care: Treatment and outcome in advanced papillary renal cell carcinoma in the prospective German clinical RCC-Registry

Abstract

Non-clear cell renal cell carcinoma is a very rare malignancy that includes several histological subtypes. Each subtype may need to be addressed separately regarding prognosis and treatment; however, no Phase III clinical trial data exist. Thus, treatment recommendations for patients with non-clear cell metastatic RCC (mRCC) remain unclear. We present first prospective data on choice of first- and second-line treatment in routine practice and outcome of patients with papillary mRCC. From the prospective German clinical cohort study (RCC-Registry), 99 patients with papillary mRCC treated with systemic first-line therapy between December 2007 and May 2017 were included. Prospectively enrolled patients who had started first-line treatment until May 15, 2016, were included into the outcome analyses (n = 82). Treatment was similar to therapies used for clear cell mRCC and consisted of tyrosine kinase inhibitors, mechanistic target of rapamycin inhibitors and recently checkpoint inhibitors. Median progression-free survival from start of first-line treatment was 5.4 months (95% confidence interval [CI], 4.1-9.2) and median overall survival was 12.0 months (95% CI, 8.1-20.0). At data cutoff, 73% of the patients died, 6% were still observed, 12% were lost to follow-up, and 9% were alive at the end of the individual 3-year observation period. Despite the lack of prospective Phase III evidence in patients with papillary mRCC, our real-world data reveal effectiveness of systemic clear cell mRCC therapy in papillary mRCC. The prognosis seems to be inferior for papillary compared to clear cell mRCC. Further studies are needed to identify drivers of effectiveness of systemic therapy for papillary mRCC.

Keywords: cohort studies; disease management; kidney neoplasms; outcome assessment; outpatients.

Figure 1

Cohort definition. Number of patients enrolled in the RCC‐Registry from December 2007 until May 2017, split up according to the histological subtypes of mRCC. Most of the patients presented with clear cell mRCC, while 7% presented with papillary mRCC comprising our total cohort (n = 99). Thereof, all patients who had started their first‐line treatment until May 15, 2016, and had provided written informed consent <12 weeks after the start of first‐line treatment were included into the outcome analyses (n = 82, outcome cohort).

Figure 2

Choice of systemic treatment over time in patients with papillary mRCC. (a) First‐line treatments from 2007 to 2017 sorted by relative frequency (n = 99). (b) Second‐line treatments from 2007 to 2017 sorted by relative frequency (n = 59). Other: Treatments not further specified, e.g., treatments within a randomised blind study.

Figure 3

Sequential treatment strategies over time in papillary mRCC. Sequential treatment pattern is presented for all patients whose first‐ and second‐line treatments were documented (n = 59). The observation period was split into two subperiods reflecting the approval and introduction of the different targeted second‐line treatment strategies (TKI, mTOR, CPI): (a) Start of second‐line treatment between 2007 and 2010 (n = 26). (b) Start of second‐line treatment between 2011 and 2017 (n = 33). Bevacizumab + interferon was included in “Other” strategies. Percentages may not add up to 100% due to rounding.

Figure 4

PFS of patients with papillary mRCC since the start of first‐line treatment. All prospectively enrolled patients who had started first‐line treatment until May 15, 2016, were included (n = 82).

Figure 5

OS of patients with papillary mRCC since the start of first‐line treatment. All prospectively enrolled patients who had started first‐line treatment until May 15, 2016, were included (n = 82).