PMID- 32276179
OWN - NLM
STAT- MEDLINE
DCOM- 20201027
LR  - 20201027
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 131
DP  - 2020 May
TI  - Weekly paclitaxel plus bevacizumab versus docetaxel as second- or third-line 
      treatment in advanced non-squamous non-small-cell lung cancer: Results of the 
      IFCT-1103 ULTIMATE study.
PG  - 27-36
LID - S0959-8049(20)30095-2 [pii]
LID - 10.1016/j.ejca.2020.02.022 [doi]
AB  - PURPOSE: Second-line chemotherapy regimens have demonstrated poor benefit after 
      failure of platinum-based chemotherapy in advanced non-squamous non-small-cell 
      lung cancer (nsNSCLC). METHODS: In this multicentre, open-label phase III trial, 
      patients with advanced nsNSCLC treated with one or two prior lines, including one 
      platinum-based doublet, were centrally randomised to receive 90 mg/m(2) of 
      paclitaxel (D1, D8, D15) plus 10 mg/kg of bevacizumab (D1, D15) every 28 days or 
      docetaxel (75 mg/m(2)) every 21 days; crossover was allowed after disease 
      progression. Primary end-point was progression-free survival (PFS). 
      ClinicalTrials.gov registration number: NCT01763671. RESULTS: One hundred sixty 
      six patients were randomised (paclitaxel plus bevacizumab: 111, docetaxel: 55). 
      The median PFS was longer in patients receiving paclitaxel plus bevacizumab than 
      in patients receveing docetaxel [5.4 months versus 3.9 months, adjusted hazard 
      ratio (HR) 0.61 (95% confidence interval [CI]: 0.44-0.86); p = 0.005]. Objective 
      response rates (ORRs) were 22.5% (95% CI: 14.8-30.3) and 5.5% (95% CI: 0.0-11.5) 
      (p = 0.006), respectively. Median overall survivals were similar (adjusted HR 
      1.17; p = 0.50). Crossover occurred in 21 of 55 (38.2%) docetaxel-treated 
      patients. Grade III-IV adverse events (AEs) were reported in 45.9% and 54.5% of 
      patients treated with paclitaxel and bevacizumab or docetaxel, respectively 
      (p = NS), including neutropenia (19.3% versus 45.4%), neuropathy (8.3% versus 
      0.0%) and hypertension (7.3% versus 0.0%). Three patients died due to 
      treatment-related AEs (1.8% in each group). CONCLUSION: Weekly paclitaxel plus 
      bevacizumab as second- or third-line improves PFS and ORR compared with docetaxel 
      in patients with nsNSCLC, with an acceptable safety profile. These results place 
      weekly paclitaxel plus bevacizumab as a valid option in this population. CLINICAL 
      TRIALS REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01763671.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Cortot, Alexis B
AU  - Cortot AB
AD  - Univ. Lille, CHU Lille, Thoracic Oncology Dept, CNRS, Inserm, Institut Pasteur de 
      Lille, UMR9020 - UMR-S 1277, Canther, F-59000, Lille, France. Electronic address: 
      alexis.cortot@chru-lille.fr.
FAU - Audigier-Valette, Clarisse
AU  - Audigier-Valette C
AD  - Service de Pneumologie, CHITS Sainte Musse, Toulon, France. Electronic address: 
      clarisse.audigier-valette@ch-toulon.fr.
FAU - Molinier, Olivier
AU  - Molinier O
AD  - Service des Maladies Respiratoires, Centre Hospitalier General, Le Mans, France. 
      Electronic address: omolinier@ch-lemans.fr.
FAU - Le Moulec, Sylvestre
AU  - Le Moulec S
AD  - Service de Pneumologie, Institut Bergonie, Bordeaux, France. Electronic address: 
      s.le-moulec@bordeaux.unicancer.fr.
FAU - Barlesi, Fabrice
AU  - Barlesi F
AD  - Aix Marseille University, Assistance Public Hopitaux de Marseille. 
      Multidisciplinary Oncology & Therapeutic Innovations Dpt, Marseille, France. 
      Electronic address: fabrice.barlesi@ap-hm.fr.
FAU - Zalcman, Gerard
AU  - Zalcman G
AD  - Service D'oncologieThoracique, Hopital Bichat Claude Bernard, Paris, France. 
      Electronic address: gerard.zalcman@aphp.fr.
FAU - Dumont, Patrick
AU  - Dumont P
AD  - Centre Hospitalier, Chauny, France. Electronic address: dr.dumont@ch-chauny.fr.
FAU - Pouessel, Damien
AU  - Pouessel D
AD  - Service D'Oncologie Medicale, Hopital Saint-Louis, Paris, France. Electronic 
      address: pouessel.damien@iuct-oncopole.fr.
FAU - Poulet, Claire
AU  - Poulet C
AD  - Service de Pneumologie, CHU - Groupe Hospitalier Sud, Amiens, France. Electronic 
      address: poulet.claire@chu-amiens.fr.
FAU - Fontaine-Delaruelle, Clara
AU  - Fontaine-Delaruelle C
AD  - Centre Hospitalier Universitaire Lyon Sud, Pierre Benite, France. Electronic 
      address: clara.fontaine-delaruelle@chu-lyon.fr.
FAU - Hiret, Sandrine
AU  - Hiret S
AD  - Institut de Cancerologie de L'Ouest - Rene Gauducheau-Saint Herblain, France. 
      Electronic address: sandrine.hiret@ico.unicancer.fr.
FAU - Dixmier, Adrien
AU  - Dixmier A
AD  - Service de Pneumologie, Centre Hospitalier Regional, Orleans, France. Electronic 
      address: adrien.dixmier@chr-orleans.fr.
FAU - Renault, Patrick-Aldo
AU  - Renault PA
AD  - Service de Pneumologie, Centre Hospitalier, Pau, France. Electronic address: 
      aldo.renault@ch-pau.fr.
FAU - Becht, Catherine
AU  - Becht C
AD  - Oncologie Medicale, Clinique de Clementville, Montpellier, France. Electronic 
      address: catherine.becht@laposte.net.
FAU - Raffy, Olivier
AU  - Raffy O
AD  - Service de Pneumologie, CH Louis Pasteur, Chartres, France. Electronic address: 
      raffy.olivier@neuf.fr.
FAU - Dayen, Charles
AU  - Dayen C
AD  - Service de Pneumologie, Centre Hospitalier, Saint Quentin, France. Electronic 
      address: c.dayen@ch-stquentin.fr.
FAU - Mazieres, Julien
AU  - Mazieres J
AD  - Service de Pneumologie, Hopital Larrey, Toulouse, France. Electronic address: 
      mazieres.j@chu-toulouse.fr.
FAU - Pichon, Eric
AU  - Pichon E
AD  - Service de Pneumologie, CHRU Bretonneau, Tours, France. Electronic address: 
      e.pichon@chu-tours.fr.
FAU - Langlais, Alexandra
AU  - Langlais A
AD  - Intergroupe Francophone de Cancerologie Thoracique (IFCT), Paris, France. 
      Electronic address: alexandra.langlais@ifct.fr.
FAU - Morin, Franck
AU  - Morin F
AD  - Intergroupe Francophone de Cancerologie Thoracique (IFCT), Paris, France. 
      Electronic address: franck.morin@ifct.fr.
FAU - Moro-Sibilot, Denis
AU  - Moro-Sibilot D
AD  - Intergroupe Francophone de Cancerologie Thoracique (IFCT), Paris, France; 
      Thoracic Oncology Unit, PTV, CHU Grenoble-Alpes CS10217, 38043, Grenoble, France. 
      Electronic address: DMoro-Sibilot@chu-grenoble.fr.
FAU - Besse, Benjamin
AU  - Besse B
AD  - Cancer Medecine Department, Gustave Roussy, Villejuif, France; Paris-Saclay 
      University, Orsay, France. Electronic address: benjamin.besse@gustaveroussy.fr.
LA  - eng
SI  - ClinicalTrials.gov/NCT01763671
PT  - Clinical Trial, Phase III
PT  - Equivalence Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200408
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 15H5577CQD (Docetaxel)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Bevacizumab/*administration & dosage/adverse effects
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/pathology
MH  - Cross-Over Studies
MH  - Disease Progression
MH  - Docetaxel/*administration & dosage/adverse effects
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Lung Neoplasms/*drug therapy/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Paclitaxel/*administration & dosage/adverse effects
MH  - Progression-Free Survival
MH  - Young Adult
OTO - NOTNLM
OT  - Bevacizumab
OT  - Docetaxel
OT  - NSCLC
OT  - Paclitaxel
COIS- Conflict of interest statement A.B.C. has reported receiveing honoraria from 
      Roche, AstraZeneca, Bristol-Myers Squibb, BoehringerIngelheim, MSD, Novartis and 
      Pfizer and travel grants from Roche, AstraZeneca, BoehringerIngelheim, Novartis 
      and Pfizer. C.A.V. has reported receiving grants, personal fees and non-financial 
      support from Roche. O.M. has received personal fees from BMS, 
      BoehringerIngelheim, Astra Zeneca, Novartis and Hoffman-Roche. F.B. has received 
      personal fees from Astra Zeneca, BMS, BoehringerIngelheim, Clovis Oncology, Eli 
      Lilly Oncology, Hoffman-Roche, Novartis, Merck, MSD, Pierre Fabre and Pfizer. 
      G.Z. has received grant from Roche and BMS, personal fees from Roche, BMS, Astra 
      Zeneca and MSD and non-financial support from BMS, Astra Zeneca and Pfizer. D.P. 
      has received personal fees from Roche Hoffman, Astellas, Lilly, Janssen, BMS, 
      Merck, Astra Zeneca, Novartis, Sanofi and Pfizer. C.F.D. has received other 
      support from MSD (CPLF 2017), Laidet Medical (ERS 2016) and BoehringerIngelheim 
      (CPLF 2016). E.P. has received personal fees and non-financial support from Astra 
      Zeneca and BMS and personal fees from Pfizer. D.M-.S. has received personal fees 
      from Roche, BMS, MSD and Eli Lilly. B.B. has received institutional grants for 
      clinical and translational research from AstraZeneca, BMS, Boehringer-Ingelheim, 
      Lilly, Pfizer, Roche-Genentech, Sanofi-Aventis, Clovis, GSK, Servier, EOS, Onxeo, 
      OncoMed, Inivata and OSE Pharma. All other authors have no conflict of interest 
      to declare.
EDAT- 2020/04/11 06:00
MHDA- 2020/10/28 06:00
CRDT- 2020/04/11 06:00
PHST- 2020/02/20 00:00 [received]
PHST- 2020/02/22 00:00 [accepted]
PHST- 2020/04/11 06:00 [pubmed]
PHST- 2020/10/28 06:00 [medline]
PHST- 2020/04/11 06:00 [entrez]
AID - S0959-8049(20)30095-2 [pii]
AID - 10.1016/j.ejca.2020.02.022 [doi]
PST - ppublish
SO  - Eur J Cancer. 2020 May;131:27-36. doi: 10.1016/j.ejca.2020.02.022. Epub 2020 Apr 
      8.