Real-world assessment of clinical outcomes of first-line treatment in metastatic papillary renal cell carcinoma.
Authors: De Vries Manon , Hamilou Zineb , Ghosh Sunita , Heng Daniel Yick Chin , Wood Lori , Basappa Naveen S. , Kollmannsberger Christian K. , Graham Jeffrey , Bhindi Bimal , Finelli Antonio , Bjarnason Georg A. , Bosse Dominick , Pouliot Frederic , Castonguay Vincent , Breau Rodney H , Saleh Ramy R. , Winquist Eric , Lalani Aly-Khan A. , Soulieres Denis 
Published: February 2025

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Background:
Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC) representing up to 15% of RCC. First line (1L) phase II trials have evaluated immunotherapy (IO) in combination with IO or tyrosine kinase inhibitors (TKI) in nccRCC, but these cohorts are heterogeneous, with few comparative results. Therefore, the specific value of IO therapy for pRCC remains unquantified.
Methods:
We conducted an analysis based on prospectively collected data from the Canadian Kidney Cancer information system (CKCis) database. The objective was to evaluate efficacy of 1L systemic therapy of metastatic pRCC with either IO based or VEGFR-TKI. Baseline characteristics, treatment outcome and safety were collected. Primary endpoint was time-to-treatment failure (TTF). Secondary endpoints included overall survival (OS), objective response rate (ORR), adverse events requiring a change in dose/schedule (TRAEs). TTF, OS and ORR were adjusted (adj) for IMDC risk groups.
Results:
Between 01/2011 to 01/2024,206 pRCC pts were treated: 70 on IO single agent or in combination IO-IO/IO-TKI and 136 with TKI monotherapy. The median follow-up was 20.6 months (mo) (range: 1.6-146.1). There were no significant differences in baseline characteristics between 2 groups, described in table. The median TTF with IO was 9.8 mo (95%CI: 4.5, 15.9) versus (vs) 5.7 mo with TKI (95%CI: 4.6, 8.1) (adj HR: 0.61 [0.42-0.89] p=0.01). The median OS was 36.9 mo with IO (95%CI: 26.5, not reached (NR)) vs 21.6 mo with TKI (95%CI: 18, 27.9) (adj HR: 0.51 [0.3-0.85], p=0.009). Among the 170 evaluable pts, ORR was 37% (95% CI: 24.2-49.9) with IO and 21.5% (95% CI: 14.1-29) with TKI (adj OR: 2.4 [1.0-5.6] p=0.04). The TKI-IO subgroup had better TTF and OS compared to TKI therapy, with 16.9 mo (95%CI: 5.5-22.6) (adj HR: 0.46 [0.26-0.82] p=0.009), and NR (95%CI: 18.9-NR) (adj HR: 0.24 [0.08-0.78] p=0.02) respectively. 28% of pts discontinued treatment. TRAEs of grade 3-5 were noted in 27% in IO group and in 73% in TKI group.
Conclusions:
This study presents comparative data on 1L treatment metastatic pRCC. It shows an improved TTF and OS in the IO group, particularly in TKI-IO treated pts. Our findings underline the need for further clinical trials evaluating 1L IO in pts with metastatic pRCC.

Baseline characteristics.

Overall cohortn = 206
IO treatmentn = 70 (34%)
TKI treatmentn = 136 (66%)

Median age (range)
67 (30-89)
69
67

Sex Male
162 (79%)
51 (73%)
111 (82%)

IMDC score Favorable Intermediate Poor Unknown
31 (20%)93 (60%)30 (19.5%)52
15 (29%)30 (58%)7 (13%)18
16 (16%)63 (62%)23 (22%)34

Prior Nephrectomy
164 (80%)
56 (80%)
108 (79%)

Sarcomatoid component
12 (8%)
5 (7%)
7 (5%)

Therapy Nivolumab + ipilimumab Pembrolizumab + axitinib Pembrolizumab + lenvatinib Pembrolizumab Nivolumab Sunitinib Pazopanib Cabozantinib Crizotinib Savolitinib m-Tor inhibitors

27 (13%)23 (11%)7 (3.5%)11 (5%)2 (1%)
88 (43%)20 (10%)8 (4%)3 (1.5%)7 (3.5%)9 (4.5%)