PMID- 29722789
OWN - NLM
STAT- MEDLINE
DCOM- 20191118
LR  - 20200407
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 29
IP  - 7
DP  - 2018 Jul 1
TI  - The importance of jointly analyzing treatment administration and toxicity 
      associated with targeted therapies: a case study of regorafenib in soft tissue 
      sarcoma patients.
PG  - 1588-1593
LID - S0923-7534(19)32107-6 [pii]
LID - 10.1093/annonc/mdy168 [doi]
AB  - BACKGROUND: Different methods have been proposed to analyze adverse events (AEs) 
      associated with targeted therapies. While these AEs lead to dose adjustments for 
      many patients, conventional reporting methods do not take drug administration 
      into consideration. This paper underlines the importance of jointly reporting AEs 
      and drug administration using prevalence, and proposes a complementary approach 
      to reporting. PATIENTS AND METHODS: The prevalence method estimates the 
      probability of progression-free patients being in a particular health state 
      (state 1: AEs with full dose; state 2: AEs with reduced dose; state 3: no AEs 
      with reduced dose) at different time points. To take into account the impact of 
      dose adjustments on efficacy, the weighted prevalence method can be used by 
      assigning utility weights to the different health states. The benefit of these 
      methods was illustrated using data from a phase II trial of regorafenib. RESULTS: 
      Only 4.6% of progression-free patients developed mucositis/stomatitis (grade >/=2) 
      at 3 months. The prevalence of patients not experiencing this AE but whose dose 
      was reduced or treatment interrupted was 58.1%. The weighted prevalence of the 
      regorafenib toxicity profile and dose reduction was higher in the control arm. 
      CONCLUSION: This case study confirms the importance of jointly analyzing AEs and 
      drug administration. The weighted prevalence approach is an average score that 
      incorporates the dimension of drug administration into AE assessment. This can be 
      helpful for regulatory agencies as well as for clinicians to evaluate the 
      benefit-risk ratio of therapies in their treatment choice. CLINICAL TRIAL: 
      NCT01900743.
FAU - Longue, M
AU  - Longue M
AD  - Department of Biostatistics, Institut Claudius Regaud, IUCT-O, Toulouse, France.
FAU - Cabarrou, B
AU  - Cabarrou B
AD  - Department of Biostatistics, Institut Claudius Regaud, IUCT-O, Toulouse, France.
FAU - Wallet, J
AU  - Wallet J
AD  - Department of Biostatistics, Centre Oscar Lambret, Lille, France.
FAU - Brodowicz, T
AU  - Brodowicz T
AD  - Comprehensive Cancer Center Vienna - MusculoSkeletal Tumors, Medical University 
      Vienna - General Hospital, Vienna, Austria.
FAU - Roche, H
AU  - Roche H
AD  - Department of Medical Oncology, Institut Claudius Regaud, IUCT-O, Toulouse, 
      France.
FAU - Boher, J M
AU  - Boher JM
AD  - Department of Biostatistics, Institut Paoli Calmette, Marseille, France.
FAU - Delord, J P
AU  - Delord JP
AD  - Department of Medical Oncology, Institut Claudius Regaud, IUCT-O, Toulouse, 
      France.
FAU - Penel, N
AU  - Penel N
AD  - Department of Medical Oncology, Centre Oscar Lambret, Lille, France.
FAU - Filleron, T
AU  - Filleron T
AD  - Department of Biostatistics, Institut Claudius Regaud, IUCT-O, Toulouse, France. 
      Electronic address: filleron.thomas@iuct-oncopole.fr.
LA  - eng
SI  - ClinicalTrials.gov/NCT01900743
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Pyridines)
RN  - 24T2A1DOYB (regorafenib)
SB  - IM
MH  - Double-Blind Method
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology/etiology
MH  - Follow-Up Studies
MH  - France/epidemiology
MH  - Humans
MH  - Molecular Targeted Therapy/*adverse effects
MH  - Mucositis/epidemiology/etiology
MH  - Phenylurea Compounds/*administration & dosage/*adverse effects
MH  - Prevalence
MH  - Prognosis
MH  - Pyridines/*administration & dosage/*adverse effects
MH  - Sarcoma/*drug therapy/pathology
MH  - Stomatitis/epidemiology/etiology
MH  - Survival Rate
EDAT- 2018/05/04 06:00
MHDA- 2019/11/19 06:00
CRDT- 2018/05/04 06:00
PHST- 2018/05/04 06:00 [pubmed]
PHST- 2019/11/19 06:00 [medline]
PHST- 2018/05/04 06:00 [entrez]
AID - S0923-7534(19)32107-6 [pii]
AID - 10.1093/annonc/mdy168 [doi]
PST - ppublish
SO  - Ann Oncol. 2018 Jul 1;29(7):1588-1593. doi: 10.1093/annonc/mdy168.