PMID- 33412465
OWN - NLM
STAT- MEDLINE
DCOM- 20210920
LR  - 20210920
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 145
DP  - 2021 Mar
TI  - Axitinib plus pembrolizumab in patients with advanced renal-cell carcinoma: 
      Long-term efficacy and safety from a phase Ib trial.
PG  - 1-10
LID - S0959-8049(20)31419-2 [pii]
LID - 10.1016/j.ejca.2020.12.009 [doi]
AB  - BACKGROUND: Axitinib plus pembrolizumab showed superior overall survival (OS), 
      progression-free survival (PFS) and objective response rate (ORR) versus 
      sunitinib in a randomised phase III trial in patients with advanced renal-cell 
      carcinoma (RCC). We report long-term efficacy and safety of the 
      axitinib/pembrolizumab from the phase I trial (NCT02133742), after 46-55 months 
      from study initiation (data cut-off date, 23rd July 2019). METHODS: Fifty-two 
      treatment-naive patients with advanced RCC were treated with oral axitinib 5 mg 
      twice daily and intravenous pembrolizumab 2 mg/kg every 3 weeks. PFS, duration of 
      response (DoR) and OS were summarised using the Kaplan-Meier method. RESULTS: At 
      a median follow-up of 42.7 months (95% confidence interval [CI]: 41.1-44.1), 
      median OS was not reached; 38 (73.1%) patients were alive. The probability of 
      being alive at 4 years was 66.8% (95% CI: 49.1-79.5). Median PFS in the overall 
      population was 23.5 months (95% CI: 15.4-30.4). ORR was 73.1%; five patients had 
      complete response. Median DoR was 22.1 months (95% CI: 15.1-34.5). Grade III/IV 
      adverse events (AEs) were reported in 38 (73.1%) patients and 20 (38.5%) 
      discontinued treatment because of AEs: 17 (32.7%) discontinued axitinib, 13 
      (25.0%) discontinued pembrolizumab, and 10 (19.2%) discontinued both drugs. 
      Common AEs included diarrhoea (84.6%), fatigue (80.8%), hypertension (53.8%), 
      cough (48.1%) and dysphonia (48.1%). There were no new AE terms reported and no 
      treatment-related deaths. CONCLUSIONS: In patients with advanced RCC with ~4 
      years of follow-up, combination axitinib/pembrolizumab continued to demonstrate 
      clinical benefit, with no new safety signals.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Atkins, Michael B
AU  - Atkins MB
AD  - Georgetown-Lombardi Comprehensive Cancer Center, 3800 Reservoir Road, NW, 
      Washington DC, 20057, USA. Electronic address: mba41@georgetown.edu.
FAU - Plimack, Elizabeth R
AU  - Plimack ER
AD  - Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA, 19111, USA. 
      Electronic address: elizabeth.plimack@fccc.edu.
FAU - Puzanov, Igor
AU  - Puzanov I
AD  - Vanderbilt University Medical Center, 1211 Medical Center Dr, Nashville, TN, 
      7232, USA; Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY, 
      14203, USA. Electronic address: Igor.Puzanov@roswellpark.org.
FAU - Fishman, Mayer N
AU  - Fishman MN
AD  - Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL, 33612, USA. 
      Electronic address: fishman@usf.edu.
FAU - McDermott, David F
AU  - McDermott DF
AD  - Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA. 
      Electronic address: dmcdermo@bidmc.harvard.edu.
FAU - Cho, Daniel C
AU  - Cho DC
AD  - Perlmutter Cancer Center at NYU Langone Medical Center, 240 E 38th St 19th floor, 
      New York, NY, 10016, USA. Electronic address: daniel.cho@nyumc.org.
FAU - Vaishampayan, Ulka
AU  - Vaishampayan U
AD  - Karmanos Cancer Institute, Wayne State University, 4100 John R St, Detroit, MI, 
      48201, USA. Electronic address: vaishamu@med.umich.edu.
FAU - George, Saby
AU  - George S
AD  - Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY, 14203, USA. 
      Electronic address: Saby.George@roswellpark.org.
FAU - Tarazi, Jamal C
AU  - Tarazi JC
AD  - Pfizer Global Product Development-Oncology, 10777 Science Center Dr, San Diego, 
      CA, 92121, USA. Electronic address: jamal.tarazi@pfizer.com.
FAU - Duggan, William
AU  - Duggan W
AD  - Pfizer Global Product Development-Oncology, 280 Shennecossett Rd, Groton, CT, 
      06340, USA. Electronic address: william.t.duggan@pfizer.com.
FAU - Perini, Rodolfo
AU  - Perini R
AD  - Merck & Co, Inc, 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, USA. Electronic 
      address: rodolfo.perini@merck.com.
FAU - Thakur, Mahgull
AU  - Thakur M
AD  - Pfizer, Discovery Park, Ramsgate Rd, Sandwich, CT13 9ND, UK. Electronic address: 
      mahgull.thakur@pfizer.com.
FAU - Fernandez, Kathrine C
AU  - Fernandez KC
AD  - Pfizer Global Product Development-Oncology, 1 Portland St, Cambridge, MA, 02139, 
      USA. Electronic address: kathrine.fernandez@pfizer.com.
FAU - Choueiri, Toni K
AU  - Choueiri TK
AD  - Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA. 
      Electronic address: Toni_Choueiri@dfci.harvard.edu.
LA  - eng
SI  - ClinicalTrials.gov/NCT02133742
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210104
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - C9LVQ0YUXG (Axitinib)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/adverse effects/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Axitinib/adverse effects/*therapeutic use
MH  - Carcinoma, Renal Cell/*drug therapy/mortality/pathology
MH  - Female
MH  - Humans
MH  - Kidney Neoplasms/*drug therapy/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Progression-Free Survival
MH  - Time Factors
MH  - United States
OTO - NOTNLM
OT  - Axitinib
OT  - Long-term
OT  - Overall survival
OT  - Pembrolizumab
OT  - Progression-free survival
OT  - Renal-cell carcinoma
OT  - Safety
COIS- Conflict of interest statement MB Atkins reports institutional research support 
      from Bristol-Myers Squibb, Merck, Pfizer, and Genentech; consulting fees from 
      Pfizer, Novartis, Genentech-Roche, Merck, Exelixis, Eisai, Boehringer Ingelheim, 
      Aveo, Array, Idera, Aduro, Immunocore, Iovance, NewLink, Pharma, Surface, 
      Alexion, Acceleron, COTA, Amgen, Up-to-Date, and AstraZeneca; roles in advisory 
      boards for Bristol-Myers Squibb, Merck, Novartis, Arrowhead, Pfizer, Glactone, 
      Werewolf, Fathom, Pneuma, Leads Pharma, Pyxis; and stock option in Werewolf and 
      Pyxis. ER Plimack reports consulting fees from and/or served roles in advisory 
      boards for Bristol-Myers Squibb, Exelixis, Genentech, Incyte, Janssen, Merck, 
      AstraZeneca, and Pfizer; and grant or clinical trial support from Astellas, 
      AstraZeneca, Bristol-Myers Squibb, Genentech, Merck, Peloton, and Pfizer. I 
      Puzanov reports consulting fees from and/or served on advisory boards for Amgen, 
      Roche, and AbbVie and clinical trial support through his institution from Merck, 
      Amgen, Roche, Nektar, Idera, and Bristol-Myers Squibb. MN Fishman reports 
      research funding from Bristol-Myers Squibb, Exelixis, Eisai, Genentech, 
      Acceleron, Merck, Prometheus / Clinigen, Nektar, Alkermes, and Pfizer; and 
      speakers bureau roles for Astellas, Bristol-Myers Squibb, Exelixis, EMD Serono, 
      Pfizer; and paid roles in advisory boards for Alkermes, Clinigen, Eisai, Merck, 
      Pfizer, Seattle Genetics. DF McDermott reports consulting fees from Bristol-Myers 
      Squibb, Pfizer, Novartis, Genentech-Roche, Merck, Eisai, Array BioPharma, 
      Prometheus, and Exelixis. DC Cho reports consulting fees from Pfizer, Genentech, 
      Prometheus, Bristol-Myers Squibb, PureTech Health, Torque Pharmaceuticals, and 
      Exelixis. U Vaishampayan reports research support from Astellas, Bristol-Myers 
      Squibb, and Exelixis and consulting fees from Exelixis, Merck, Alkermes, Pfizer, 
      Pfizer, Bayer, and Bristol-Myers Squibb. S George reports consulting fees from 
      and advisory roles for Pfizer, Exelixis, Bristol-Myers Squibb, Sanofi/Genzyme, 
      Genentech, Bayer, Corvus, EMD Serono, Seattle Genetics/Astellas, Eisai, and Merck 
      and institutional grant support from Bristol-Myers Squibb, Novartis, Bayer, 
      Pfizer, Merck, Seattle Genetics/Astellas, Eisai, Calithera Biosciences, 
      Immunomedics, Corvus Pharmaceuticals, and Agensys. JC Tarazi, W Duggan, M Thakur, 
      and KC Fernandez reports being employees of Pfizer and stock or stock options in 
      Pfizer. R Perini reports an employee of Merck Sharp & Dohme Corp., a subsidiary 
      of Merck & Co., Inc., Kenilworth, NJ, USA. TK Choueiri reports research support 
      (institutional and personal) from AstraZeneca, Alexion, Bayer, Bristol-Myers 
      Squibb/E.R. Squibb & Sons LLC, Cerulean, Eisai, Foundation Medicine Inc, 
      Exelixis, Ipsen, TRACON, Genentech, Roche, Roche Products Ltd, F. Hoffmann-La 
      Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, Prometheus, Corvus, 
      Calithera, Analysis Group, Sanofi/Aventis, Takeda, National Cancer Institute 
      (NCI), National Institutes of Health (NIH), and Department of Defense (DOD); 
      honoraria from AstraZeneca, Alexion, Sanofi/Aventis, Bayer, Bristol-Myers 
      Squibb/E.R. Squibb & Sons LLC, Cerulean, Eisai, Foundation Medicine Inc, 
      Exelixis, Genentech, Roche, Roche Products Ltd, F. Hoffmann-La Roche, 
      GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus, 
      Corvus, Ipsen, Up-to-Date, Analysis Group, National Comprehensive Cancer Network 
      (NCCN), Michael J. Hennessy (MJH) Associates Inc, Research to Practice, Lpath, 
      Kidney Cancer journal, Clinical Care Options, PlatformQ, Navinata Health, 
      Harborside Press, American Society of Medical Oncology, New England Journal of 
      Medicine, Lancet Oncology, Heron Therapeutics, Lilly, American Society of 
      Clinical Oncology (ASCO), and European Society of Medical Oncology (ESMO); 
      provided consultancy or advisory services to AstraZeneca, Alexion, 
      Sanofi/Aventis, Bayer, Bristol-Myers Squibb/E.R. Squibb & Sons LLC, Cerulean, 
      Eisai, Foundation Medicine Inc, Exelixis, Genentech, Heron Therapeutics, Lilly, 
      Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus, 
      Corvus, Ipsen, Up-to-Date, NCCB, Analysis Group, Pionyr, and Tempest; stock 
      ownership in Pionyr and Tempest; contributions toward International Patent 
      Application No. PCT/US2018/12,209, entitled "PBRM1 Biomarkers Predictive of 
      Anti-Immune Checkpoint Response," filed January 3, 2018, claiming priority to 
      U.S. Provisional Patent Application No. 62/445,094, filed January 11, 2017, and 
      International Patent Application No. PCT/US2018/058,430, entitled "Biomarkers of 
      Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy," filed 
      October 31, 2018, claiming priority to U.S. Provisional Patent Application No. 
      62/581,175, filed November 3, 2017; and travel, accommodations, and expenses in 
      relation to consulting, advisory roles, and/or honoraria.
EDAT- 2021/01/08 06:00
MHDA- 2021/09/21 06:00
CRDT- 2021/01/07 20:16
PHST- 2020/11/18 00:00 [received]
PHST- 2020/12/01 00:00 [accepted]
PHST- 2021/01/08 06:00 [pubmed]
PHST- 2021/09/21 06:00 [medline]
PHST- 2021/01/07 20:16 [entrez]
AID - S0959-8049(20)31419-2 [pii]
AID - 10.1016/j.ejca.2020.12.009 [doi]
PST - ppublish
SO  - Eur J Cancer. 2021 Mar;145:1-10. doi: 10.1016/j.ejca.2020.12.009. Epub 2021 Jan 
      4.