PMID- 34875200
OWN - NLM
STAT- MEDLINE
DCOM- 20220211
LR  - 20220430
IS  - 1744-7658 (Electronic)
IS  - 1354-3784 (Linking)
VI  - 30
IP  - 12
DP  - 2021 Dec
TI  - Combination therapies in clinical trials for renal cell carcinoma: how could they 
      impact future treatments?
PG  - 1221-1229
LID - 10.1080/13543784.2021.2014814 [doi]
AB  - INTRODUCTION: Pharmacological combinations using immune checkpoint inhibition 
      (ICI), tyrosine kinase inhibition (TKIs), and mammalian target of rapamycin 
      inhibitors (mTOR) have improved survival in metastatic clear cell renal cell 
      cancer (mccRCC). Despite improvements in survival, complete durable responses are 
      rare. AREAS COVERED: Molecular pathways involved in mccRCC and drugs targets are 
      highlighted. The background and rationale for combination therapy are covered. 
      Results from combination trials are reviewed and potential approaches with 
      biomarker-stratified treatment and novel experimental agents are examined. PubMed 
      Central and ClinicalTrials.gov were searched. Search terms used to identify 
      clinical trials were '(metastatic renal cell cancer OR renal cell carcinoma OR 
      mccRCC OR mRCC OR RCC OR kidney cancer) AND (combination OR combined).' EXPERT 
      OPINION: First-line standard of care has moved to combination therapy with 
      ICI-ICI and TKI-ICI combinations; VEGF-mTORi is available in subsequent lines. 
      Combining targeted treatments without validated biomarkers is imprecise, and 
      combinations may lead to overtreatment of a subset of patients, exposing them to 
      unnecessary toxicity. The aim of combinations must be clear: improvement in 
      overall survival (OS) and complete response (CR). Recent data suggest a role for 
      novel biomarker stratification rather traditional risk groups. Further 
      combination approaches with triplets and quadruplets should be biomarker 
      directed.
FAU - Ince, Will
AU  - Ince W
AUID- ORCID: 0000-0002-2122-7760
AD  - Department of Oncology, Addenbrookes's Hospital, Cambridge, UK.
FAU - Eisen, Tim
AU  - Eisen T
AD  - Department of Oncology, Addenbrookes's Hospital, Cambridge, UK.
LA  - eng
PT  - Journal Article
DEP - 20220104
PL  - England
TA  - Expert Opin Investig Drugs
JT  - Expert opinion on investigational drugs
JID - 9434197
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - *Carcinoma, Renal Cell/drug therapy
MH  - Combined Modality Therapy
MH  - Humans
MH  - *Kidney Neoplasms/drug therapy
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Protein-Tyrosine Kinases
OTO - NOTNLM
OT  - Combination trials
OT  - VEGF-IO combination
OT  - immunotherapy
OT  - mRCC
OT  - mccRCC
OT  - metastatic renal cell cancer
EDAT- 2021/12/08 06:00
MHDA- 2022/02/12 06:00
CRDT- 2021/12/07 20:10
PHST- 2021/12/08 06:00 [pubmed]
PHST- 2022/02/12 06:00 [medline]
PHST- 2021/12/07 20:10 [entrez]
AID - 10.1080/13543784.2021.2014814 [doi]
PST - ppublish
SO  - Expert Opin Investig Drugs. 2021 Dec;30(12):1221-1229. doi: 
      10.1080/13543784.2021.2014814. Epub 2022 Jan 4.