Stereotactic Radiotherapy and Short-course Pembrolizumab for Oligometastatic Renal Cell Carcinoma-The RAPPORT Trial.

Antibodies, Monoclonal, Humanized / adverse effects Carcinoma, Renal Cell / therapy Female Humans Kidney Neoplasms / therapy Male Neoplasm Recurrence, Local Radiosurgery / adverse effects Treatment Outcome
Clear cell Immunotherapy Kidney cancer Metastasis-directed therapy Radiation therapy Stereotactic body radiotherapy

Journal

European urology
ISSN: 1873-7560
Titre abrégé: Eur Urol
Pays: Switzerland
ID NLM: 7512719

Informations de publication

Date de publication:
Apr 2022
Historique:
received: 17 09 2021
revised: 08 11 2021
accepted: 03 12 2021
pubmed: 27 12 2021
medline: 19 4 2022
entrez: 26 12 2021
Statut: ppublish

Résumé

Stereotactic ablative body radiotherapy (SABR) is an option for oligometastatic clear cell renal cell carcinoma (ccRCC) but is limited by a lack of prospective clinical trial data. The RAPPORT trial evaluated the safety and efficacy of total metastatic irradiation followed by short-course anti-programmed death receptor-1 immunotherapy in patients with oligometastatic ccRCC. RAPPORT was a single-arm multi-institutional phase I/II trial (NCT02855203). Patients with two or fewer lines of prior systemic therapy and one to five oligometastases from ccRCC were eligible. A single fraction of 20 Gy SABR (or if not feasible, ten fractions of 3 Gy) was given to all metastatic sites, followed by pembrolizumab 200 mg administered Q3W for eight cycles. The endpoints were adverse events (AEs), disease control rate (DCR) for at least 6 mo, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The Kaplan-Meier method was used for time-to-event endpoints. Freedom from local progression (FFLP) was assessed per lesion adding patient as a cluster effect. Thirty evaluable patients, with a median age of 62 yr, were enrolled. The median follow-up was 28 mo. There were 44% of patients with intermediate-risk and 56% with favorable-risk disease. Eighty-three oligometastases were irradiated (median three per patient): eight adrenal, 11 bone, 43 lung, 12 lymph node, and nine soft tissue. Four patients (13%) had grade 3 treatment-related AEs: pneumonitis (n = 2), dyspnea (n = 1), and elevated alkaline phosphatase/alanine transaminase (n = 1). There were no grade 4 or 5 AEs. FFLP at 2 yr was 92%. ORR was 63% and DCR was 83%. Estimated 1- and 2-yr OS was 90% and 74%, respectively, and PFS was 60% and 45%, respectively. Limitations include a single-arm design and selected patient population. SABR and short-course pembrolizumab in oligometastatic ccRCC is well tolerated, with excellent local control. Durable responses and encouraging PFS were observed, warranting further investigation. The RAPPORT trial investigated the combination of high-dose precision radiotherapy and a short course of immunotherapy in patients with low-volume metastatic kidney cancer. We found that this treatment regimen was well tolerated, with excellent cancer control in sites of known disease. A proportion of patients were free from cancer relapse in the longer term, and these encouraging findings warrant further investigation.

Sections du résumé

BACKGROUND BACKGROUND
Stereotactic ablative body radiotherapy (SABR) is an option for oligometastatic clear cell renal cell carcinoma (ccRCC) but is limited by a lack of prospective clinical trial data.
OBJECTIVE OBJECTIVE
The RAPPORT trial evaluated the safety and efficacy of total metastatic irradiation followed by short-course anti-programmed death receptor-1 immunotherapy in patients with oligometastatic ccRCC.
DESIGN SETTING, AND PARTICIPANTS METHODS
RAPPORT was a single-arm multi-institutional phase I/II trial (NCT02855203). Patients with two or fewer lines of prior systemic therapy and one to five oligometastases from ccRCC were eligible.
INTERVENTION METHODS
A single fraction of 20 Gy SABR (or if not feasible, ten fractions of 3 Gy) was given to all metastatic sites, followed by pembrolizumab 200 mg administered Q3W for eight cycles.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS METHODS
The endpoints were adverse events (AEs), disease control rate (DCR) for at least 6 mo, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The Kaplan-Meier method was used for time-to-event endpoints. Freedom from local progression (FFLP) was assessed per lesion adding patient as a cluster effect.
RESULTS AND LIMITATIONS CONCLUSIONS
Thirty evaluable patients, with a median age of 62 yr, were enrolled. The median follow-up was 28 mo. There were 44% of patients with intermediate-risk and 56% with favorable-risk disease. Eighty-three oligometastases were irradiated (median three per patient): eight adrenal, 11 bone, 43 lung, 12 lymph node, and nine soft tissue. Four patients (13%) had grade 3 treatment-related AEs: pneumonitis (n = 2), dyspnea (n = 1), and elevated alkaline phosphatase/alanine transaminase (n = 1). There were no grade 4 or 5 AEs. FFLP at 2 yr was 92%. ORR was 63% and DCR was 83%. Estimated 1- and 2-yr OS was 90% and 74%, respectively, and PFS was 60% and 45%, respectively. Limitations include a single-arm design and selected patient population.
CONCLUSIONS CONCLUSIONS
SABR and short-course pembrolizumab in oligometastatic ccRCC is well tolerated, with excellent local control. Durable responses and encouraging PFS were observed, warranting further investigation.
PATIENT SUMMARY RESULTS
The RAPPORT trial investigated the combination of high-dose precision radiotherapy and a short course of immunotherapy in patients with low-volume metastatic kidney cancer. We found that this treatment regimen was well tolerated, with excellent cancer control in sites of known disease. A proportion of patients were free from cancer relapse in the longer term, and these encouraging findings warrant further investigation.

Identifiants

DOI: 10.1016/j.eururo.2021.12.006 PMID: 34953600
pubmed: 34953600
pii: S0302-2838(21)02214-4
doi: 10.1016/j.eururo.2021.12.006
pii:
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
pembrolizumab DPT0O3T46P

Banques de données

ClinicalTrials.gov
['NCT02855203']

Types de publication

Clinical Trial, Phase I Clinical Trial, Phase II Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

364-372

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2021 European Association of Urology. All rights reserved.

Auteurs

Shankar Siva (S)

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. Electronic address: Shankar.Siva@petermac.org.

Mathias Bressel (M)

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Simon T Wood (ST)

Princess Alexandra Hospital, Brisbane, QLD, Australia; University of Queensland, Brisbane, QLD, Australia.

Mark G Shaw (MG)

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Sherene Loi (S)

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

Shahneen K Sandhu (SK)

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

Ben Tran (B)

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

Arun A Azad (A)

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

Jeremy H Lewin (JH)

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Katharine E Cuff (KE)

Princess Alexandra Hospital, Brisbane, QLD, Australia; University of Queensland, Brisbane, QLD, Australia.

Howard Y Liu (HY)

Princess Alexandra Hospital, Brisbane, QLD, Australia; University of Queensland, Brisbane, QLD, Australia.

Daniel Moon (D)

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Department of Surgery, University of Melbourne, Melbourne, VIC, Australia.

Jeremy Goad (J)

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Lih-Ming Wong (LM)

Department of Surgery, University of Melbourne, Melbourne, VIC, Australia.

Michael LimJoon (M)

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Jennifer Mooi (J)

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Sarat Chander (S)

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Declan G Murphy (DG)

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

Nathan Lawrentschuk (N)

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Department of Surgery, University of Melbourne, Melbourne, VIC, Australia.

David Pryor (D)

Princess Alexandra Hospital, Brisbane, QLD, Australia; Queensland University of Technology, Brisbane, QLD, Australia.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Stereotactic Radiotherapy and Short-course...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Tumeurs urologiques › Tumeurs du rein › Néphrocarcinome › Stereotactic Radiotherapy and Short-course...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Stereotactic Radiotherapy and Short-course...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Tumeurs urologiques › Tumeurs du rein › Stereotactic Radiotherapy and Short-course...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Récidive tumorale locale › Stereotactic Radiotherapy and Short-course...
questionsmedicales.fr › Techniques d'investigation › Techniques stéréotaxiques › Radiochirurgie › Stereotactic Radiotherapy and Short-course...
questionsmedicales.fr › Qualité, accès, évaluation des soins de santé › Qualité des soins de santé › Mécanismes d'évaluation des soins de santé › Évaluation des résultats et des processus en soins de santé › Évaluation de résultat (soins) › Résultat thérapeutique › Stereotactic Radiotherapy and Short-course...