Incidence of myelodysplastic syndrome and acute myeloid leukemia in patients receiving poly-ADP ribose polymerase inhibitors for the treatment of solid tumors: A meta-analysis of randomized trials.
Journal
Gynecologic oncology
ISSN: 1095-6859
Titre abrégé: Gynecol Oncol
Pays: United States
ID NLM: 0365304
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
22
01
2021
accepted:
05
03
2021
pubmed:
20
3
2021
medline:
4
1
2022
entrez:
19
3
2021
Statut:
ppublish
Résumé
Clinical trials demonstrated that PARPi (poly [adenosine diphosphate-ribose]-ADP polymerase inhibitor) therapy is effective in solid tumors. However, long term effects such as therapy-related myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) are poorly described. We sought to quantify whether PARPi therapy is associated with the development of MDS/AML. Medline, Embase, and Cochrane databases were searched (inception to January 6, 2020) and phase 2 and 3 clinical trials that randomized patients with solid tumors to a PARPi or control therapy were included. The PRISMA guidelines were used to extract data independently by multiple authors. We extracted person-time and number of cases of MDS/AML in the PARPi and control arms of each study and pooled results with a random-effects Poisson regression model. The pooled incidence rate ratio (IRR) for MDS/AML among patients randomized to PARPi therapy was compared to those randomized to a control. We identified 14 studies that included 5739 patients. Accounting for intra-study clustering, the risk of MDS/AML was similar in patients who were randomly assigned to receive PARPi compared to controls (IRR 1.32, 95% confidence interval [CI] 0.78-2.26). In the front-line setting, PARPi therapy was associated with developing MDS/AML (IRR 5.43, 95% CI 1.51-19.60). Among patients treated for recurrence, however, the risk of MDS/AML appeared to be similar among patients randomized to PARPi or control treatment. Among studies that included only patients with a BRCA mutation, the risk of MDS/AML was similar in both treatment groups (IRR 0.83, 95% CI 0.45-1.53), but PARPi therapy was associated with MDS/AML in studies with an unrestricted population (IRR 2.43, 95% CI 1.17-5.06). The pooled overall effect was not statistically significant. However, treatment with PARPi was associated with a statistically significant increase in the incidence of MDS/AML among patients receiving front-line cancer therapy and those with limited prior exposure to chemotherapy.
Sections du résumé
BACKGROUND
Clinical trials demonstrated that PARPi (poly [adenosine diphosphate-ribose]-ADP polymerase inhibitor) therapy is effective in solid tumors. However, long term effects such as therapy-related myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) are poorly described. We sought to quantify whether PARPi therapy is associated with the development of MDS/AML.
METHODS
Medline, Embase, and Cochrane databases were searched (inception to January 6, 2020) and phase 2 and 3 clinical trials that randomized patients with solid tumors to a PARPi or control therapy were included. The PRISMA guidelines were used to extract data independently by multiple authors. We extracted person-time and number of cases of MDS/AML in the PARPi and control arms of each study and pooled results with a random-effects Poisson regression model. The pooled incidence rate ratio (IRR) for MDS/AML among patients randomized to PARPi therapy was compared to those randomized to a control.
RESULTS
We identified 14 studies that included 5739 patients. Accounting for intra-study clustering, the risk of MDS/AML was similar in patients who were randomly assigned to receive PARPi compared to controls (IRR 1.32, 95% confidence interval [CI] 0.78-2.26). In the front-line setting, PARPi therapy was associated with developing MDS/AML (IRR 5.43, 95% CI 1.51-19.60). Among patients treated for recurrence, however, the risk of MDS/AML appeared to be similar among patients randomized to PARPi or control treatment. Among studies that included only patients with a BRCA mutation, the risk of MDS/AML was similar in both treatment groups (IRR 0.83, 95% CI 0.45-1.53), but PARPi therapy was associated with MDS/AML in studies with an unrestricted population (IRR 2.43, 95% CI 1.17-5.06).
CONCLUSION
The pooled overall effect was not statistically significant. However, treatment with PARPi was associated with a statistically significant increase in the incidence of MDS/AML among patients receiving front-line cancer therapy and those with limited prior exposure to chemotherapy.
Identifiants
pubmed: 33736856
pii: S0090-8258(21)00231-6
doi: 10.1016/j.ygyno.2021.03.011
pmc: PMC8164998
mid: NIHMS1683877
pii:
doi:
Substances chimiques
Poly(ADP-ribose) Polymerase Inhibitors
0
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
653-659Subventions
Organisme : NCI NIH HHS
ID : K08 CA234333
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR001874
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA101642
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Références
J Clin Oncol. 2014 Dec 1;32(34):3840-7
pubmed: 25349301
N Engl J Med. 2012 Apr 12;366(15):1382-92
pubmed: 22452356
N Engl J Med. 2011 Jan 20;364(3):205-14
pubmed: 21208101
Blood. 2013 Apr 11;121(15):2996-3004
pubmed: 23412096
J Clin Oncol. 2020 Oct 20;38(30):3468-3493
pubmed: 32790492
Ann Oncol. 2019 Apr 1;30(4):558-566
pubmed: 30689707
J Clin Epidemiol. 2017 Nov;91:129-136
pubmed: 28802674
JAMA Oncol. 2019 Mar 1;5(3):318-325
pubmed: 30570657
Lancet Oncol. 2017 Sep;18(9):1274-1284
pubmed: 28754483
Biom J. 2020 Nov;62(7):1597-1630
pubmed: 32510177
J Clin Oncol. 2019 Nov 10;37(32):2968-2973
pubmed: 31173551
Lancet. 2017 Oct 28;390(10106):1949-1961
pubmed: 28916367
PLoS Med. 2009 Jul 21;6(7):e1000097
pubmed: 19621072
J Neurooncol. 2017 Jan;131(1):105-115
pubmed: 27655223
Ann Oncol. 2018 Jan 1;29(1):154-161
pubmed: 29045554
BMC Med Res Methodol. 2015 Apr 30;15:42
pubmed: 25925169
Clin Cancer Res. 2017 Apr 15;23(8):1937-1944
pubmed: 27803064
Lancet Oncol. 2015 Jan;16(1):87-97
pubmed: 25481791
Gynecol Oncol. 2018 Nov;151(2):190-195
pubmed: 30268525
N Engl J Med. 2019 Dec 19;381(25):2403-2415
pubmed: 31562800
Lancet Oncol. 2016 Nov;17(11):1579-1589
pubmed: 27617661
Cancer. 2016 Jan 15;122(2):304-11
pubmed: 26641009
J Clin Oncol. 2018 Aug 10;36(23):2386-2394
pubmed: 29906251
Lancet Oncol. 2018 Apr;19(4):497-509
pubmed: 29501363
N Engl J Med. 2016 Jul 7;375(1):23-34
pubmed: 27406347
N Engl J Med. 2016 Dec;375(22):2154-2164
pubmed: 27717299
Br J Cancer. 2018 Oct;119(9):1075-1085
pubmed: 30353045
JAMA Oncol. 2017 Jul 1;3(7):936-943
pubmed: 28152123
Ann Oncol. 2014 Nov;25(11):2156-2162
pubmed: 25139550
Breast Cancer Res Treat. 2015 Nov;154(2):351-7
pubmed: 26536871
Nat Rev Cancer. 2017 Aug 24;17(9):513-527
pubmed: 28835720
N Engl J Med. 2019 Dec 19;381(25):2416-2428
pubmed: 31851799
Lancet Haematol. 2021 Feb;8(2):e122-e134
pubmed: 33347814
Biom J. 2016 Nov;58(6):1428-1444
pubmed: 27546483
Gynecol Oncol. 2020 Nov;159(2):442-448
pubmed: 32981695
J Med Genet. 2012 Jul;49(7):422-8
pubmed: 22652532
BMJ. 2019 Aug 28;366:l4898
pubmed: 31462531
N Engl J Med. 2019 Jul 25;381(4):317-327
pubmed: 31157963
Stat Med. 2015 Mar 30;34(7):1097-116
pubmed: 25446971
JAMA. 2000 Apr 19;283(15):2008-12
pubmed: 10789670
Clin Cancer Res. 2015 Oct 1;21(19):4257-61
pubmed: 26187614
N Engl J Med. 2018 Dec 27;379(26):2495-2505
pubmed: 30345884
J Clin Oncol. 2012 Feb 1;30(4):372-9
pubmed: 22203755
Blood. 2016 Jan 21;127(3):310-3
pubmed: 26644450
N Engl J Med. 2017 Aug 10;377(6):523-533
pubmed: 28578601
J Clin Oncol. 2020 Apr 10;38(11):1164-1174
pubmed: 32073956
N Engl J Med. 2019 Dec 19;381(25):2391-2402
pubmed: 31562799
N Engl J Med. 2018 Aug 23;379(8):753-763
pubmed: 30110579