PMID- 34035370
OWN - NLM
STAT- MEDLINE
DCOM- 20211105
LR  - 20211105
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 May 25
TI  - Efficacy, safety and tolerability of drugs studied in phase 3 randomized 
      controlled trials in solid tumors over the last decade.
PG  - 10843
LID - 10.1038/s41598-021-90403-3 [doi]
LID - 10843
AB  - Data suggest that for newly approved cancer drugs safety and tolerability are 
      worse than in control arms of registration trials. Less is known about the 
      balance between efficacy and toxicity of drugs studied in unselected phase 3 
      randomized controlled trials (RCTs) including those not resulting in regulatory 
      approval. We searched Clinicaltrials.gov to identify phase 3 RCTs in patients 
      with advanced breast, colorectal, lung, or prostate cancer completed between 
      January 2005 and October 2016. We extracted efficacy and safety data from 
      publications. For efficacy hazard ratios (HRs) for progression-free survival 
      (PFS) and overall survival (OS) were extracted. For safety, we computed odds 
      ratios (ORs) and 95% confidence intervals (CIs) for toxic death, treatment 
      discontinuation without progression and commonly reported grade 3/4 adverse 
      events (AEs). Data were then pooled in a meta-analysis. Of 377 RCTs identified 
      initially, 143 RCTs comprising 88,603 patients were included in the analysis. Of 
      these, 79 (57%) trials met their primary endpoint. Compared to control groups, 
      both PFS (HR 0.80; 95% CI 0.78-0.82) and OS (HR 0.87; 95% CI 0.85-0.89) were 
      improved with experimental drugs. Toxic death (OR 1.14; 95% CI 1.03-1.27), 
      treatment discontinuation without progression (OR 1.64; 95% CI 1.56-1.71) and 
      grade 3/4 AEs were also more common with experimental drugs compared to 
      respective control group therapy. Just over half of phase 3 RCTs in common solid 
      tumors met their primary endpoint and in nearly half, experimental therapy had 
      worse safety compared to control arms.
FAU - Ribnikar, Domen
AU  - Ribnikar D
AD  - Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, 
      Slovenia.
AD  - Division of Medical Oncology and Hematology, University of Toronto and Princess 
      Margaret Cancer Centre, 610 University Ave, 700U, 7-721, Toronto, ON, M5G 2M9, 
      Canada.
FAU - Goldvaser, Hadar
AU  - Goldvaser H
AD  - Division of Medical Oncology and Hematology, University of Toronto and Princess 
      Margaret Cancer Centre, 610 University Ave, 700U, 7-721, Toronto, ON, M5G 2M9, 
      Canada.
AD  - Rabin Medical Center, Davidoff Cancer Center, Beilinson Hospital, Petah Tikva, 
      Israel.
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Veitch, Zachary W
AU  - Veitch ZW
AD  - Division of Medical Oncology and Hematology, University of Toronto and Princess 
      Margaret Cancer Centre, 610 University Ave, 700U, 7-721, Toronto, ON, M5G 2M9, 
      Canada.
FAU - Ocana, Alberto
AU  - Ocana A
AD  - Drug Development Program, Hospital Clinico San Carlos and CIBERONC, Madrid, 
      Spain.
AD  - Translational Oncology Laboratory. Regional Center for Biomedical Research 
      (CRIB), Castilla La Mancha University, Albacete, Spain.
FAU - Templeton, Arnoud J
AU  - Templeton AJ
AD  - Department of Oncology, St. Claraspital Basel, Basel, Switzerland.
AD  - Faculty of Medicine, University of Basel, Basel, Switzerland.
FAU - Seruga, Bostjan
AU  - Seruga B
AD  - Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, 
      Slovenia.
FAU - Amir, Eitan
AU  - Amir E
AD  - Division of Medical Oncology and Hematology, University of Toronto and Princess 
      Margaret Cancer Centre, 610 University Ave, 700U, 7-721, Toronto, ON, M5G 2M9, 
      Canada. eitan.amir@uhn.ca.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
DEP - 20210525
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Antineoplastic Agents/adverse effects/*therapeutic use
MH  - Clinical Trials, Phase III as Topic
MH  - Female
MH  - Humans
MH  - Male
MH  - Neoplasms/*drug therapy
MH  - Odds Ratio
MH  - Randomized Controlled Trials as Topic
MH  - Survival Analysis
MH  - Treatment Outcome
PMC - PMC8149406
COIS- The authors declare no competing interests.
EDAT- 2021/05/27 06:00
MHDA- 2021/11/06 06:00
PMCR- 2021/05/25
CRDT- 2021/05/26 06:31
PHST- 2020/04/29 00:00 [received]
PHST- 2021/04/30 00:00 [accepted]
PHST- 2021/05/26 06:31 [entrez]
PHST- 2021/05/27 06:00 [pubmed]
PHST- 2021/11/06 06:00 [medline]
PHST- 2021/05/25 00:00 [pmc-release]
AID - 10.1038/s41598-021-90403-3 [pii]
AID - 90403 [pii]
AID - 10.1038/s41598-021-90403-3 [doi]
PST - epublish
SO  - Sci Rep. 2021 May 25;11(1):10843. doi: 10.1038/s41598-021-90403-3.