PMID- 35799149
OWN - NLM
STAT- MEDLINE
DCOM- 20220711
LR  - 20230916
IS  - 1741-7015 (Electronic)
IS  - 1741-7015 (Linking)
VI  - 20
IP  - 1
DP  - 2022 Jul 8
TI  - Risk and benefit for umbrella trials in oncology: a systematic review and 
      meta-analysis.
PG  - 219
LID - 10.1186/s12916-022-02420-2 [doi]
LID - 219
AB  - BACKGROUND: Umbrella clinical trials in precision oncology are designed to tailor 
      therapies to the specific genetic changes within a tumor. Little is known about 
      the risk/benefit ratio for umbrella clinical trials. The aim of our systematic 
      review with meta-analysis was to evaluate the efficacy and safety profiles in 
      cancer umbrella trials testing targeted drugs or a combination of targeted 
      therapy with chemotherapy. METHODS: Our study was prospectively registered in 
      PROSPERO (CRD42020171494). We searched Embase and PubMed for cancer umbrella 
      trials testing targeted agents or a combination of targeted therapies with 
      chemotherapy. We included solid tumor studies published between 1 January 2006 
      and 7 October 2019. We measured the risk using drug-related grade 3 or higher 
      adverse events (AEs), and the benefit by objective response rate (ORR), 
      progression-free survival (PFS), and overall survival (OS). When possible, data 
      were meta-analyzed. RESULTS: Of the 6207 records identified, we included 31 
      sub-trials or arms of nine umbrella trials (N = 1637). The pooled overall ORR was 
      17.7% (95% confidence interval [CI] 9.5-25.9). The ORR for targeted therapies in 
      the experimental arms was significantly lower than the ORR for a combination of 
      targeted therapy drugs with chemotherapy: 13.3% vs 39.0%; p = 0.005. The median 
      PFS was 2.4 months (95% CI 1.9-2.9), and the median OS was 7.1 months (95% CI 
      6.1-8.4). The overall drug-related death rate (drug-related grade 5 AEs rate) was 
      0.8% (95% CI 0.3-1.4), and the average drug-related grade 3/4 AE rate per person 
      was 0.45 (95% CI 0.40-0.50). CONCLUSIONS: Our findings suggest that, on average, 
      one in five cancer patients in umbrella trials published between 1 January 2006 
      and 7 October 2019 responded to a given therapy, while one in 125 died due to 
      drug toxicity. Our findings do not support the expectation of increased patient 
      benefit in cancer umbrella trials. Further studies should investigate whether 
      umbrella trial design and the precision oncology approach improve patient 
      outcomes.
CI  - (c) 2022. The Author(s).
FAU - Strzebonska, Karolina
AU  - Strzebonska K
AD  - Research Ethics in Medicine Study Group (REMEDY), Faculty of Health Sciences, 
      Jagiellonian University Medical College, Krakow, Poland.
FAU - Blukacz, Mateusz
AU  - Blukacz M
AD  - Institute of Psychology, University of Silesia, Katowice, Poland.
AD  - Institute of Public Health, Faculty of Health Sciences, Jagiellonian University 
      Medical College, Krakow, Poland.
FAU - Wasylewski, Mateusz T
AU  - Wasylewski MT
AD  - Research Ethics in Medicine Study Group (REMEDY), Faculty of Health Sciences, 
      Jagiellonian University Medical College, Krakow, Poland.
FAU - Polak, Maciej
AU  - Polak M
AD  - Research Ethics in Medicine Study Group (REMEDY), Faculty of Health Sciences, 
      Jagiellonian University Medical College, Krakow, Poland.
AD  - Department of Epidemiology and Population Studies, Institute of Public Health, 
      Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, 
      Poland.
FAU - Gyawali, Bishal
AU  - Gyawali B
AD  - Department of Oncology and the Department of Public Health Sciences, Queen's 
      University, Kingston, Ontario, Canada.
FAU - Waligora, Marcin
AU  - Waligora M
AD  - Research Ethics in Medicine Study Group (REMEDY), Faculty of Health Sciences, 
      Jagiellonian University Medical College, Krakow, Poland. m.waligora@uj.edu.pl.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
DEP - 20220708
PL  - England
TA  - BMC Med
JT  - BMC medicine
JID - 101190723
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - *Antineoplastic Agents/adverse effects
MH  - Humans
MH  - Medical Oncology
MH  - *Neoplasms/chemically induced/drug therapy
MH  - Precision Medicine
PMC - PMC9264503
OTO - NOTNLM
OT  - Ethics
OT  - Risk-benefit balance
OT  - Targeted therapy
OT  - Umbrella trial
COIS- Marcin Waligora reports personal fees from the Advisory Bioethics Council 
      (Sanofi) outside the submitted work. Karolina Strzebonska, Mateusz Blukacz, 
      Mateusz T. Wasylewski, Maciej Polak, and Bishal Gyawali declare that they have no 
      competing interests.
EDAT- 2022/07/08 06:00
MHDA- 2022/07/12 06:00
PMCR- 2022/07/08
CRDT- 2022/07/07 23:44
PHST- 2021/12/03 00:00 [received]
PHST- 2022/05/30 00:00 [accepted]
PHST- 2022/07/07 23:44 [entrez]
PHST- 2022/07/08 06:00 [pubmed]
PHST- 2022/07/12 06:00 [medline]
PHST- 2022/07/08 00:00 [pmc-release]
AID - 10.1186/s12916-022-02420-2 [pii]
AID - 2420 [pii]
AID - 10.1186/s12916-022-02420-2 [doi]
PST - epublish
SO  - BMC Med. 2022 Jul 8;20(1):219. doi: 10.1186/s12916-022-02420-2.