. 2025 Sep 1;30(9):oyaf240.

doi: 10.1093/oncolo/oyaf240.

Real-world assessment of clinical outcomes of first-line treatment in metastatic papillary renal cell carcinoma

Manon De Vries-Brilland^{1

2}, Zineb Hamilou², Sunita Ghosh³, Daniel Y C Heng⁴, Lori A Wood⁵, Naveen S Basappa⁶, Christian K Kollmannsberger⁷, Jeffrey Graham⁸, Bimal Bhindi⁹, Antonio Finelli¹⁰, Georg A Bjarnason¹¹, Dominick Bosse¹², Frederic Pouliot¹³, Vincent Castonguay¹⁴, Rodney H Breau¹⁵, Ramy R Saleh¹⁶, Eric Winquist¹⁷, Aly-Khan A Lalani¹⁸, Denis Soulières²

Affiliations

¹ Department of Medical Oncology, Integrated Centers of Oncology (ICO) Paul Papin, Angers 49055, France.
² Centre Hospitalier de l'Université de Montréal, Montreal, QC H3C 3J7, Canada.
³ Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada.
⁴ Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 2T9, Canada.
⁵ Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS B3H 2Y9, Canada.
⁶ Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada.
⁷ British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC V5Z 4E6, Canada.
⁸ CancerCare Manitoba, University of Manitoba, Winnipeg, MB R3E 0V9, Canada.
⁹ Southern Alberta Institute of Urology, University of Calgary, Calgary, AB T2V 1P9, Canada.
¹⁰ Division of Urology, Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada.
¹¹ Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
¹² Division of Medical Oncology, Department of Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada.
¹³ CHU de Quebec, Université Laval, Quebec City, QC G1R 2J6, Canada.
¹⁴ Hotel Dieu de Quebec, Quebec, QC G1R 2J6, Canada.
¹⁵ Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada.
¹⁶ Department of Medical Oncology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
¹⁷ Division of Medical Oncology, London Health Sciences Centre & Western University, London, ON N6A 5W9, Canada.
¹⁸ Department of Medical Oncology, McMaster University, Hamilton, ON L8S 4L8Canada.

PMID: 40757924
PMCID: PMC12445671
DOI: 10.1093/oncolo/oyaf240

Real-world assessment of clinical outcomes of first-line treatment in metastatic papillary renal cell carcinoma

Manon De Vries-Brilland et al. Oncologist. 2025.

. 2025 Sep 1;30(9):oyaf240.

doi: 10.1093/oncolo/oyaf240.

Authors

Affiliations

¹ Department of Medical Oncology, Integrated Centers of Oncology (ICO) Paul Papin, Angers 49055, France.
² Centre Hospitalier de l'Université de Montréal, Montreal, QC H3C 3J7, Canada.
³ Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada.
⁴ Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 2T9, Canada.
⁵ Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS B3H 2Y9, Canada.
⁶ Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada.
⁷ British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC V5Z 4E6, Canada.
⁸ CancerCare Manitoba, University of Manitoba, Winnipeg, MB R3E 0V9, Canada.
⁹ Southern Alberta Institute of Urology, University of Calgary, Calgary, AB T2V 1P9, Canada.
¹⁰ Division of Urology, Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada.
¹¹ Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
¹² Division of Medical Oncology, Department of Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada.
¹³ CHU de Quebec, Université Laval, Quebec City, QC G1R 2J6, Canada.
¹⁴ Hotel Dieu de Quebec, Quebec, QC G1R 2J6, Canada.
¹⁵ Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada.
¹⁶ Department of Medical Oncology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
¹⁷ Division of Medical Oncology, London Health Sciences Centre & Western University, London, ON N6A 5W9, Canada.
¹⁸ Department of Medical Oncology, McMaster University, Hamilton, ON L8S 4L8Canada.

PMID: 40757924
PMCID: PMC12445671
DOI: 10.1093/oncolo/oyaf240

Abstract

Background: Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC), representing up to 15% of RCC cases. Phase 2 trials have evaluated first-line (1L) immunotherapy (IO)-based treatment in nccRCC, but with heterogeneous cohorts and limited comparative data. The specific value of IO for metastatic pRCC (mpRCC) remains unquantified.

Methods: We analyzed prospectively collected data from the Canadian Kidney Cancer Information System to assess the efficacy of 1L systemic therapy in mpRCC with IO-based regimens vs tyrosine kinase inhibitors (TKI). The primary endpoint was time-to-treatment failure (TTF). Secondary endpoints included overall survival (OS), objective response rate (ORR), and treatment-related adverse events (TRAEs). Analyses were adjusted (adj) for IMDC risk groups.

Results: From 2011 to 2024, 197 mpRCC patients received 1L therapy: 70 with IO (alone or in combination) and 127 with TKI. Median follow-up was 21.6 months. Median TTF was 9.9 months with IO vs 5.9 months with TKI (adjHR: 0.62 [0.43-0.91], P = .01). Median OS was 36.9 months with IO vs 23.2 months with TKI (adjHR: 0.54 [0.3-0.9], P = .018). Objective response rate was 37% with IO vs 23% with TKI (adjOR: 2.2 [0.95-5.2], P = .07). The TKI-IO subgroup showed the longest TTF (16.9 months, adjHR: 0.47 [0.26-0.85], P = .01) and OS (not reached, adjHR: 0.26 [0.08-0.83], P = .02), compared to TKI. Grade 3-5 TRAEs occurred in 31% (IO) vs 27% (TKI).

Conclusions: This real-world study highlights the benefit of IO-based treatment in mpRCC, particularly in the TKI-IO subgroup. Our findings may inform further trials evaluating 1L IO in mpRCC.

Keywords: CKCis; TKI; first-line systemic treatment; immunotherapy; metastatic papillary renal-cell cancer.

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Conflict of interest statement

M.D.V.-B.: consulting: AstraZeneca, BMS/travel: AstraZeneca.

Z.H.: None.

S.G.: None.

D.Y.C.H.: Consulting: Pfizer, Novartis, BMS, Janssen, Astellas pharma, Ipsen, Eisai, Merck/Research funding for his institution: Pfizer, Exelixis, Novartis, BMS, Ipsen.

L.A.W.: Research funding for her institution: BMS, Pfizer, Roche Canada, Merck, AstraZeneca.

N.S.B.: Consulting: Pfizer, BMS, Janssen, Astellas pharma, Ipsen, AstraZeneca, Eisai, Merck, Bayer, EMD Serono, Seagen/Travel: Eisai, Ipsen, Janssen, Pfizer/Honoraria: Pfizer, Janssen, Astellas pharma, Ipsen, AstraZeneca, Eisai, Merck, Bayer, Seagen, Takeda/Research funding for his institution: Ipsen/Stock ownership: illumiSonics.

C.K.K.: Consulting: Pfizer, BMS, Janssen, Astellas pharma, Eisai, Merck, Bayer, Seagen, AAA-Novartis, Gilead sciences, Ipsen/Travel: Ipsen, AAA Canada, Pfizer, Janssen/Honoraria: Pfizer, BMS, Janssen, Ipsen, Merck, Astellas pharma, Eisai, Seagen, Bayer.

J.G.: Consulting: Janssen, Ipsen, AstraZeneca, Merck, EMD Serono/Honoraria: Ipsen, Pfizer, Merck, Janssen.

B.B.: Consulting: Janssen, Bayer, Ferring, Verity Pharmaceuticals/Honoraria: Merck, Bayer.

A.F.: Consulting: Amgen, Astellas Pharma, Janssen, Bayer, AbbVie, TerSera/Honoraria: Amgen, Astellas Pharma, Janssen, Bayer, AbbVie, TerSera, Merck/Stock ownership: AbbVie, Medtronic.

G.A.B.: Consulting: Pfizer, BMS, Eisai, Ipsen/Honoraria: Pfizer, BMS, Eisai, Ipsen, Merck/Research funding for his institution: Pfizer, Merck.

D.B.: Consulting: BMS, AbbVie, Pfizer, Bayer, Ipsen, AstraZeneca, Merck, Astellas pharma, Knight Therapeutics/Travel: Knight Therapeutics, Ipsen, Janssen, EMD Serono/Honoraria: Amgen, Ipsen, Janssen, AstraZeneca, BMS, Pfizer, Eisai, Bayer, Merck, EMD Serono/Research funding: Ipsen.

F.P.: Consulting: Astellas pharma, Bayer, Janssen, Tolmar, TerSera, Merck, AstraZeneca/Speakers’ Bureau: Bayer, Astellas pharma, Janssen, Novartis/Patents, Royalties, Other Intellectual Property/Stock ownership: Allogene Therapeutics/Honoraria: Astellas pharma, Janssen, Bayer, AstraZeneca, Tolmar, Novartis, TerSera/Research funding for his institution: Astellas pharma, TerSera, Janssen, Merck, Novartis.

V.C.: Consulting: AstraZeneca, BMS, Ipsen, Janssen, Eisai, Pfizer, Astellas pharma, Merck, Bayer, GlaxoSmithKline Canada/Research funding for his institution: Merck, Pfizer, AstraZeneca, Bayer, BMS.

R.H.B.: None.

R.R.S.: None.

E.W.: Consulting: Merck, Bayer, Roche, Eisai, Ipsen, EMD Serono/Research funding for his institution: Merck, Novartis, Lilly.

A.-K.A.L.: Consulting: Eisai, Merck, Ipsen, Pfizer, BMS, AbbVie, Janssen, Bayer, Astellas pharma, Novartis/Honoraria: Pfizer, Roche, Merck, Novartis, Astellas pharma, Bayer, BMS, Eisai, Ipsen/Research funding for his institution: BMS, Novartis, Roche, Ipsen, EMD Serono, BioCanRx.

D.S.: Consulting: Merck, Pfizer, Ipsen, Adlai Nortye, Eisai/Honoraria: Merck, Novartis, Pfizer, AstraZeneca, BMS, Ipsen, Eisai, Adlai Nortye, Bicara Therapeutics/Research funding for his institution: Novartis, Pfizer, Merck, Roche, BMS, Lilly, Adlai Nortye, GlaxoSmithKline.

Figures

**Figure 1.**
Kaplan-Meier curves for time-to-treatment failure for patients with metastatic papillary renal cell carcinoma receiving first-line immuno-oncology (IO)-based combinations or tyrosine kinase inhibitors (TKIs).

**Figure 2.**
Kaplan-Meier curves for overall survival for patients with metastatic papillary renal cell carcinoma receiving first-line immuno-oncology (IO)-based combinations or tyrosine kinase inhibitors (TKIs).

**Figure 3.**
Kaplan-Meier curves for time-to-treatment failure for patients with metastatic papillary renal cell carcinoma receiving first-line IO-IO combination or tyrosine kinase inhibitors (TKIs) (A) and receiving first-line IO-TKI combination or TKI (B). IO, immuno-oncology.

**Figure 4.**
Kaplan-Meier curves for overall survival for patients with metastatic papillary renal cell carcinoma receiving first-line IO-IO combination or tyrosine kinase inhibitors (TKI) (A) and receiving first-line IO-TKI combination or TKI (B). IO, immuno-oncology.

See this image and copyright information in PMC

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Real-world assessment of clinical outcomes of first-line treatment in metastatic papillary renal cell carcinoma

Affiliations

Real-world assessment of clinical outcomes of first-line treatment in metastatic papillary renal cell carcinoma

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical