Efficacy of targeted therapies after PD-1/PD-L1 blockade in metastatic renal cell carcinoma.
BACKGROUND
Monoclonal antibodies that target the programmed death-1 (PD-1)/programmed death-ligand 1(PD-L1) pathway have shown antitumour activity in metastatic renal cell carcinoma (mRCC) and are currently being developed in first-line (in combination) and in previously treated patients. The efficacy targeted therapy (TT) after PD-1/PD-L1 blockade is still unknown.


METHODS
Medical records of mRCC patients treated with investigational PD-1 or PD-L1 inhibitors at 4 academic institutions were reviewed. Patients who received subsequent treatment with TT were selected to collect outcome measures of subsequent TT.


RESULTS
Of 99 patients who received PD-1/PD-L1 blockade as part of clinical trials, 56 patients have received subsequent therapy: 44 patients received vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) inhibitors and 12 received mammalian target of rapamycin (mTOR) inhibitors as first subsequent TT. Median follow up, from the start of subsequent TT was 16.1 months (range: 0.2, 30.6 months). TT post PD-1/PD-L1 blockade was administered as second-line, third-line or beyond third-line in 9 (16%), 24 (43%) and 23 patients (41%) respectively. Median time to treatment failure on subsequent TT was 6.6 months (range: 0.2+, 23.0). 1-year and 2 year overall survival from the initiation of subsequent TT was 58% (95% confidence interval (CI): 41-72%) and 36% (95% CI: 18-54%), respectively.


CONCLUSIONS
Both VEGF/VEGFR and mTOR inhibitors demonstrate antitumour activity following PD-1/PD-L1 blockade.
Kidney Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, United States; Gustave Roussy Cancer Campus, University of Paris Sud, Department of Cancer Medicine, Villejuif, France.
Laurence
L
Albiges
Kidney Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, United States.
André P
AP
Fay
Kidney Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, United States.
Wanling
W
Xie
Kidney Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, United States.
Katherine
K
Krajewski
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States; Kidney Cancer Program, Dana-Farber Harvard Cancer Center, Boston, United States.
David F
DF
McDermott
Tom Baker Cancer Center and University of Calgary, Calgary, Canada.
Daniel Y C
DY
Heng
Gustave Roussy Cancer Campus, University of Paris Sud, Department of Cancer Medicine, Villejuif, France.
Charles
C
Dariane
Kidney Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, United States.
Guillermo
G
DeVelasco
Kidney Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, United States.
Renee
R
Lester
Gustave Roussy Cancer Campus, University of Paris Sud, Department of Cancer Medicine, Villejuif, France.
Bernard
B
Escudier
Kidney Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, United States; Kidney Cancer Program, Dana-Farber Harvard Cancer Center, Boston, United States. Electronic address: Toni_Choueiri@dfci.harvard.edu.
Toni K
TK
Choueiri
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D009362:Neoplasm Metastasis; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism; D055815:Young Adult
D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases
PD-1; PD-L1; Renal cell carcinoma; Targeted therapy; VEGFR; mTOR