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Stereotactic ablative body radiotherapy in combination with pembrolizumab shows efficacy in first-line for oligometastatic clear cell renal cell carcinoma

Results of the phase I/II RAPPORT trial demonstrate the feasibility of stereotactic ablative body radiotherapy followed by pembrolizumab as a treatment modality for patients with oligometastatic clear cell renal cell carcinoma. The results obtained in this study compare favourably to the results obtained with pembrolizumab alone in this setting and justify further evaluation of this treatment modality in patients with ccRCC.

Introduction

Stereotactic ablative body radiotherapy (SABR) is a treatment option for patients with oligometastatic clear cell renal cell carcinoma (ccRCC), however, patients often experience distant progression. Although it is not the current standard of care (SoC), the PD-1 inhibitor pembrolizumab did demonstrate clinical activity in previously untreated advanced ccRCC patients with an overall response rate (ORR) of 34% and a median progression-free survival (PFS) of 7.1 months (KEYNOTE-427). In the phase I/II RAPPORT trial, the combination of SABR with pembrolizumab is being studied as a treatment modality for ccRCC patients with oligometastatic disease.

This single arm trial enrolled 30 oligometastatic ccRCC patients to receive SABR to all metastatic sites (20Gy single dose, or 30Gy across 10 fractions of conventional radiotherapy [CRT] if SABR was not feasible) followed by pembrolizumab (200 mg every 3 weeks) for 8 cycles. The primary endpoint of this study was safety, but the study also looked into f PFS, overall survival (OS), disease control rate (DCR) and ORR as secondary study objectives.

SABR and pembrolizumab induces an ORR of 63%

The median age of participants in this study was 62 years and 77% of them were being male. More than three quarters (77%) of patients did not receive prior therapy. 30% underwent a metastasectomy and 20 % received prior therapy with a tyrosine kinase inhibitor. A total of 83 oligometastatic sites were irradiated (median 3 per patient), of which 77% received SABR and 33% received CRT. This included 8 adrenal, 11 bone, 43 lung, 12 lymph node and 9 soft tissue metastases. All 8 cycles of pembrolizumab were completed by 80% of patients. Thirteen had to discontinue pembrolizumab due to pneumonitis and a further 7% discontinued due to disease progression. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 13% of patients, with the most common TRAEs being pneumonitis (N=2), dyspnoea (N=1) and elevated ALP/ALT (N=1). No grade 4/5 AEs were reported.

At a median follow-up of 2.3 years, an ORR of 63% was achieved with the therapeutic combination, including 40% complete responders (CR) and 23% of patients obtaining a partial response (PR). The DCR was reported at 83%. The median OS was not reached at time of this analysis, with 1- and 2-year OS estimates of 90% and 74%, respectively. The median PFS was 15.6 months, with 1- and 2-year estimated PFS rates of 60% and 45%, respectively. Median duration of response (DoR) was also not reached, with 6- and 12-month reported at 84% and 72%, respectively.

Conclusion

This single-arm, phase I/II study successfully demonstrated the safety and efficacy of SABR in combination with pembrolizumab in oligometastatic ccRCC patients. The results obtained from RAPPORT demonstrate excellent local control and durable responses, which warrant further investigation in this first-line metastatic setting.

Reference

Siva S et al., Stereotactic radiotherapy and pembrolizumab for oligometastatic renal tumours: The RAPPORT trial. Presented at ASCO GU 2021; Abstract 277.

Speaker Shankar Siva

Shankar Siva

Shankar Siva, PhD, Peter MacCallum Cancer Centre, Victoria, Australia

 

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Speaker Joshua Bauml

Joshua Bauml

Joshua Bauml, MD, University Hospital Pennsylvania, Philadelphia, USA

 

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Speaker Joshua Bauml

Joshua Bauml

Joshua Bauml, MD, University Hospital Pennsylvania, Philadelphia, USA

 

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Ian Chau

Ian Chau, MD,Royal Marsden Hospital, London & Surrey, UK

 

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Speaker Ian Chau

Ian Chau

Ian Chau, MD,Royal Marsden Hospital, London & Surrey, UK

 

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Zhong-Yu Yuan

Zhong-Yu Yuan, MD, Sun Yat-Sen University Cancer Centre, Guangzhou, China

 

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Speaker Zhong-Yu Yuan

Zhong-Yu Yuan

Zhong-Yu Yuan, MD, Sun Yat-Sen University Cancer Centre, Guangzhou, China

 

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Rui-Hua Xu

Rui-Hua Xu, MD, PhD, Sun Yat-Sen University Cancer Centre, China

 

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Rui-Hua Xu

Rui-Hua Xu, MD, PhD, Sun Yat-Sen University Cancer Centre, China

 

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Reinhard Dummer

Reinhard Dummer, MD, University Hospital Zürich, Zürich, Switzerland

 

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Speaker Reinhard Dummer

Reinhard Dummer

Reinhard Dummer, MD, University Hospital Zürich, Zürich, Switzerland

 

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Heather A. Wakelee

Heather A. Wakelee, MD, Stanford University Medical Centre, California, USA

 

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Heather A. Wakelee

Heather A. Wakelee, MD, Stanford University Medical Centre, California, USA

 

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Linda Mileshkin

Linda Mileshkin, MD, PhD, Peter MacCallum Cancer Centre, Victoria, Australia

 

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Speaker Linda Mileshkin

Linda Mileshkin

Linda Mileshkin, MD, PhD, Peter MacCallum Cancer Centre, Victoria, Australia

 

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Michael J. Morris

Michael J. Morris, MD, Memorial Sloan Kettering Cancer Center, New York, USA

 

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Michael J. Morris

Michael J. Morris, MD, Memorial Sloan Kettering Cancer Center, New York, USA

 

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Sébastien Perreault

Sébastien Perreault, MD, FRCPC, CHU Sainte Justine, Montreal, Canada

 

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Sébastien Perreault

Sébastien Perreault, MD, FRCPC, CHU Sainte Justine, Montreal, Canada

 

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Andrew Tutt

Andrew Tutt, MB ChB, PhD, FmedSci, Institute of Cancer Research, Kings College London

 

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Speaker Andrew Tutt

Andrew Tutt

Andrew Tutt, MB ChB, PhD, FmedSci, Institute of Cancer Research, Kings College London

 

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Dominik Paul Modest

Dominik Paul Modest, MD, Charité – Universitätsmedizin Berlin, Berlin, Germany

 

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Dominik Paul Modest

Dominik Paul Modest, MD, Charité – Universitätsmedizin Berlin, Berlin, Germany

 

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Toni Choueiri

Toni K. Choueiri, MD, Dana-Farber Cancer Institute, Boston, MA, USA

 

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Toni Choueiri

Toni K. Choueiri, MD, Dana-Farber Cancer Institute, Boston, MA, USA

 

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Marcia S. Brose

Marcia S. Brose, MD, PhD, FASCO, Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA

 

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Marcia S. Brose

Marcia S. Brose, MD, PhD, FASCO, Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA

 

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Patrick Roth

Patrick Roth, MD, University Hospital Zürich, Zürich, Switzerland

 

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Patrick Roth

Patrick Roth, MD, University Hospital Zürich, Zürich, Switzerland

 

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Takayuki Yoshino

Takayuki Yoshino, MD, National Cancer Center Hospital East, Kashiwa, Japan

 

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Takayuki Yoshino

Takayuki Yoshino, MD, National Cancer Center Hospital East, Kashiwa, Japan

 

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Evan J. Lipson

Evan J. Lipson, MD, PhD, Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA

 

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Evan J. Lipson

Evan J. Lipson, MD, PhD, Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA

 

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Patrick Roth

Patrick Roth, MD, University Hospital Zürich, Zürich, Switzerland

 

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Patrick Roth

Patrick Roth, MD, University Hospital Zürich, Zürich, Switzerland

 

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Takayuki Yoshino

Takayuki Yoshino, MD, National Cancer Center Hospital East, Kashiwa, Japan

 

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Takayuki Yoshino

Takayuki Yoshino, MD, National Cancer Center Hospital East, Kashiwa, Japan

 

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Joshua Bauml

Joshua Bauml, MD, University Hospital Pennsylvania, Philadelphia, USA

 

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Speaker Joshua Bauml

Joshua Bauml

Joshua Bauml, MD, University Hospital Pennsylvania, Philadelphia, USA

 

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Andrew Tutt

Andrew Tutt, MB ChB, PhD, FmedSci, Institute of Cancer Research, Kings College London

 

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Andrew Tutt

Andrew Tutt, MB ChB, PhD, FmedSci, Institute of Cancer Research, Kings College London

 

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Margaret Tempero

Margaret Tempero, MD, Department of Medicine, University of California San Francisco, United States

 

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Margaret Tempero

Margaret Tempero, MD, Department of Medicine, University of California San Francisco, United States

 

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Eleni Gkika

Eleni Gkika, MD, University of Freiburg, Freiburg, Germany

 

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Eleni Gkika

Eleni Gkika, MD, University of Freiburg, Freiburg, Germany

 

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Julien Taieb

Julien Taieb, MD, PhD, European Hospital Group Georges-Pompidou, Paris, France

 

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Julien Taieb

Julien Taieb, MD, PhD, European Hospital Group Georges-Pompidou, Paris, France

 

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Thierry André, MD, PhD, Hôpital Saint Antoine, Assistance Publique Hôpitaux de Paris and Sorbonne Université, Paris, France

 

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Thierry André

Thierry André, MD, PhD, Hôpital Saint Antoine, Assistance Publique Hôpitaux de Paris and Sorbonne Université, Paris, France

 

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Ghassan K. Abou-Alfa

Ghassan K. Abou-Alfa, MD, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, United States

 

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Ghassan K. Abou-Alfa

Ghassan K. Abou-Alfa, MD, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, United States

 

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Jonathan Strosberg

Jonathan Strosberg, MD, Moffitt Cancer Center, Tampa FL, United States

 

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Jonathan Strosberg

Jonathan Strosberg, MD, Moffitt Cancer Center, Tampa FL, United States

 

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Manish A. Shah, MD, Weill Cornell Medicine, New York, USA

 

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Manish A. Shah

Manish A. Shah, MD, Weill Cornell Medicine, New York, USA

 

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Yelena Y. Janjigian

Yelena Y. Janjigian, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, United States

 

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Michele Maio, MD, PhD, University Hospital of Siena, Italy

 

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Michele Maio

Michele Maio, MD, PhD, University Hospital of Siena, Italy

 

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Michel Ducreux, MD, PhD, Gustave Roussy, Villejuif, Université Paris Saclay, France

 

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Michel Ducreux, MD, PhD, Gustave Roussy, Villejuif, Université Paris Saclay, France

 

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Jaffer Ajani, MD, University of Texas MD Anderson Cancer Center, Houston, United States

 

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Jaffer Ajani

Jaffer Ajani, MD, University of Texas MD Anderson Cancer Center, Houston, United States

 

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Yu Sunakawa

Yu Sunakawa, MD, PhD, St. Marianna University School of Medicine, Kawasaki, Japan

 

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Yu Sunakawa

Yu Sunakawa, MD, PhD, St. Marianna University School of Medicine, Kawasaki, Japan

 

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Margaret Tempero

Margaret Tempero, MD, Department of Medicine, University of California San Francisco, United States

 

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Speaker Margaret Tempero

Margaret Tempero

Margaret Tempero, MD, Department of Medicine, University of California San Francisco, United States

 

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Manish A. Shah

Manish A. Shah, MD, Weill Cornell Medicine, New York, USA

 

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Manish A. Shah

Manish A. Shah, MD, Weill Cornell Medicine, New York, USA

 

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Michel Ducreux

Michel Ducreux, MD, PhD, Gustave Roussy, Villejuif, Université Paris Saclay, France

 

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Michel Ducreux

Michel Ducreux, MD, PhD, Gustave Roussy, Villejuif, Université Paris Saclay, France

 

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