PMID- 26446908
OWN - NLM
STAT- MEDLINE
DCOM- 20160920
LR  - 20181202
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 37
DP  - 2015 Nov 24
TI  - Influence of companion diagnostics on efficacy and safety of targeted anti-cancer 
      drugs: systematic review and meta-analyses.
PG  - 39538-49
LID - 10.18632/oncotarget.5946 [doi]
AB  - BACKGROUND: Companion diagnostics aim to identify patients that will respond to 
      targeted therapies, therefore increasing the clinical efficacy of such drugs. 
      Less is known about their influence on safety and tolerability of targeted 
      anti-cancer agents. METHODS AND FINDINGS: Randomized trials evaluating targeted 
      agents for solid tumors approved by the US Food and Drug Administration since 
      year 2000 were assessed. Odds ratios (OR) and and 95% confidence intervals (CI) 
      were computed for treatment-related death, treatment-discontinuation related to 
      toxicity and occurrence of any grade 3/4 adverse events (AEs). The 12 most 
      commonly reported individual AEs were also explored. ORs were pooled in a 
      meta-analysis. Analysis comprised 41 trials evaluating 28 targeted agents. 
      Seventeen trials (41%) utilized companion diagnostics. Compared to control 
      groups, targeted drugs in experimental arms were associated with increased odds 
      of treatment discontinuation, grade 3/4 AEs, and toxic death irrespective of 
      whether they utilized companion diagnostics or not. Compared to drugs without 
      available companion diagnostics, agents with companion diagnostics had a lower 
      magnitude of increased odds of treatment discontinuation (OR = 1.12 vs. 1.65, p < 
      0.001) and grade 3/4 AEs (OR = 1.09 vs. 2.10, p < 0.001), but no difference in 
      risk of toxic death (OR = 1.40 vs. 1.27, p = 0.69). Differences between agents 
      with and without companion diagnostics were greatest for diarrhea (OR = 1.29 vs. 
      2.43, p < 0.001), vomiting (OR = 0.86 vs. 1.44, p = 0.005), cutaneous toxicity 
      (OR = 1.82 vs. 3.88, p < 0.001) and neuropathy (OR = 0.64 vs. 1.60, p < 0.001). 
      CONCLUSIONS: Targeted drugs with companion diagnostics are associated with 
      improved safety, and tolerability. Differences were most marked for 
      gastrointestinal, cutaneous and neurological toxicity.
FAU - Ocana, Alberto
AU  - Ocana A
AD  - Department of Medical Oncology and Hematology, Kantonsspital St. Gallen, 
      Switzerland.
FAU - Ethier, Josee-Lyne
AU  - Ethier JL
AD  - Department of Medical Oncology, Institute of Oncology, Ljubljana, Slovenia.
FAU - Diez-Gonzalez, Laura
AU  - Diez-Gonzalez L
AD  - Department of Medical Oncology and Hematology, Kantonsspital St. Gallen, 
      Switzerland.
FAU - Corrales-Sanchez, Veronica
AU  - Corrales-Sanchez V
AD  - Department of Medical Oncology and Hematology, Kantonsspital St. Gallen, 
      Switzerland.
FAU - Srikanthan, Amirrtha
AU  - Srikanthan A
AD  - Department of Medical Oncology, Institute of Oncology, Ljubljana, Slovenia.
FAU - Gascon-Escribano, Maria J
AU  - Gascon-Escribano MJ
AD  - Department of Medical Oncology and Hematology, Kantonsspital St. Gallen, 
      Switzerland.
FAU - Templeton, Arnoud J
AU  - Templeton AJ
AD  - Department of Medical Oncology and Hematology, CancerCare Manitoba and University 
      of Manitoba, Winnipeg, Canada.
FAU - Vera-Badillo, Francisco
AU  - Vera-Badillo F
AD  - Department of Medical Oncology, Institute of Oncology, Ljubljana, Slovenia.
FAU - Seruga, Bostjan
AU  - Seruga B
AD  - Centro de Investigacion del Cancer CIC-CSIC, Universidad de Salamanca, Salamanca, 
      Spain.
FAU - Niraula, Saroj
AU  - Niraula S
FAU - Pandiella, Atanasio
AU  - Pandiella A
FAU - Amir, Eitan
AU  - Amir E
AD  - Department of Medical Oncology, Institute of Oncology, Ljubljana, Slovenia.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PT  - Systematic Review
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Antineoplastic Agents/adverse effects/*therapeutic use
MH  - Diarrhea/chemically induced
MH  - Drug Approval
MH  - Humans
MH  - Molecular Targeted Therapy/*methods
MH  - Neoplasms/diagnosis/*drug therapy
MH  - Nervous System Diseases/chemically induced
MH  - Precision Medicine/methods
MH  - Randomized Controlled Trials as Topic
MH  - Skin Diseases/chemically induced
MH  - Treatment Outcome
MH  - United States
MH  - United States Food and Drug Administration
MH  - Vomiting/chemically induced
PMC - PMC4741844
OTO - NOTNLM
OT  - cancer drugs
OT  - companion diagnostics
OT  - efficacy
OT  - trial design
COIS- CONFLICTS OF INTEREST No authors have any competing interests. An ethics 
      statement was not required for this work. No funding was received for this work.
EDAT- 2015/10/09 06:00
MHDA- 2016/09/22 06:00
PMCR- 2015/11/24
CRDT- 2015/10/09 06:00
PHST- 2015/08/01 00:00 [received]
PHST- 2015/09/06 00:00 [accepted]
PHST- 2015/10/09 06:00 [entrez]
PHST- 2015/10/09 06:00 [pubmed]
PHST- 2016/09/22 06:00 [medline]
PHST- 2015/11/24 00:00 [pmc-release]
AID - 5946 [pii]
AID - 10.18632/oncotarget.5946 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Nov 24;6(37):39538-49. doi: 10.18632/oncotarget.5946.