PMID- 34953600
OWN - NLM
STAT- MEDLINE
DCOM- 20220418
LR  - 20220811
IS  - 1873-7560 (Electronic)
IS  - 0302-2838 (Linking)
VI  - 81
IP  - 4
DP  - 2022 Apr
TI  - Stereotactic Radiotherapy and Short-course Pembrolizumab for Oligometastatic 
      Renal Cell Carcinoma-The RAPPORT Trial.
PG  - 364-372
LID - S0302-2838(21)02214-4 [pii]
LID - 10.1016/j.eururo.2021.12.006 [doi]
AB  - 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: 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: 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: 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: 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: 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: 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: 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.
CI  - Copyright (c) 2021 European Association of Urology. All rights reserved.
FAU - Siva, Shankar
AU  - Siva S
AD  - 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.
FAU - Bressel, Mathias
AU  - Bressel M
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
FAU - Wood, Simon T
AU  - Wood ST
AD  - Princess Alexandra Hospital, Brisbane, QLD, Australia; University of Queensland, 
      Brisbane, QLD, Australia.
FAU - Shaw, Mark G
AU  - Shaw MG
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
FAU - Loi, Sherene
AU  - Loi S
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; The Sir Peter MacCallum 
      Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
FAU - Sandhu, Shahneen K
AU  - Sandhu SK
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; The Sir Peter MacCallum 
      Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
FAU - Tran, Ben
AU  - Tran B
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; The Sir Peter MacCallum 
      Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
FAU - A Azad, Arun
AU  - A Azad A
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; The Sir Peter MacCallum 
      Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
FAU - Lewin, Jeremy H
AU  - Lewin JH
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
FAU - Cuff, Katharine E
AU  - Cuff KE
AD  - Princess Alexandra Hospital, Brisbane, QLD, Australia; University of Queensland, 
      Brisbane, QLD, Australia.
FAU - Liu, Howard Y
AU  - Liu HY
AD  - Princess Alexandra Hospital, Brisbane, QLD, Australia; University of Queensland, 
      Brisbane, QLD, Australia.
FAU - Moon, Daniel
AU  - Moon D
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Department of Surgery, 
      University of Melbourne, Melbourne, VIC, Australia.
FAU - Goad, Jeremy
AU  - Goad J
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
FAU - Wong, Lih-Ming
AU  - Wong LM
AD  - Department of Surgery, University of Melbourne, Melbourne, VIC, Australia.
FAU - LimJoon, Michael
AU  - LimJoon M
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
FAU - Mooi, Jennifer
AU  - Mooi J
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
FAU - Chander, Sarat
AU  - Chander S
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
FAU - Murphy, Declan G
AU  - Murphy DG
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; The Sir Peter MacCallum 
      Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
FAU - Lawrentschuk, Nathan
AU  - Lawrentschuk N
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Department of Surgery, 
      University of Melbourne, Melbourne, VIC, Australia.
FAU - Pryor, David
AU  - Pryor D
AD  - Princess Alexandra Hospital, Brisbane, QLD, Australia; Queensland University of 
      Technology, Brisbane, QLD, Australia.
LA  - eng
SI  - ClinicalTrials.gov/NCT02855203
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20211223
PL  - Switzerland
TA  - Eur Urol
JT  - European urology
JID - 7512719
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
CIN - Eur Urol. 2022 Apr;81(4):373-374. PMID: 35063309
CIN - J Urol. 2022 Sep;208(3):732-734. PMID: 35757922
MH  - Antibodies, Monoclonal, Humanized/adverse effects
MH  - *Carcinoma, Renal Cell/therapy
MH  - Female
MH  - Humans
MH  - *Kidney Neoplasms/therapy
MH  - Male
MH  - Neoplasm Recurrence, Local
MH  - *Radiosurgery/adverse effects/methods
MH  - Treatment Outcome
OTO - NOTNLM
OT  - *Clear cell
OT  - *Immunotherapy
OT  - *Kidney cancer
OT  - *Metastasis-directed therapy
OT  - *Radiation therapy
OT  - *Stereotactic body radiotherapy
EDAT- 2021/12/27 06:00
MHDA- 2022/04/19 06:00
CRDT- 2021/12/26 20:25
PHST- 2021/09/17 00:00 [received]
PHST- 2021/11/08 00:00 [revised]
PHST- 2021/12/03 00:00 [accepted]
PHST- 2021/12/27 06:00 [pubmed]
PHST- 2022/04/19 06:00 [medline]
PHST- 2021/12/26 20:25 [entrez]
AID - S0302-2838(21)02214-4 [pii]
AID - 10.1016/j.eururo.2021.12.006 [doi]
PST - ppublish
SO  - Eur Urol. 2022 Apr;81(4):364-372. doi: 10.1016/j.eururo.2021.12.006. Epub 2021 
      Dec 23.