Evaluation of the relevance of the growth modulation index (GMI) from the FFCD 0307 randomized phase III trial comparing the sequence of two chemotherapeutic regimens.
growth modulation index
precision medicine
progression-free survival ratio
survival endpoints
therapeutic sequence
Journal
ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
24
03
2023
revised:
07
07
2023
accepted:
08
07
2023
medline:
29
8
2023
pubmed:
6
8
2023
entrez:
5
8
2023
Statut:
ppublish
Résumé
Precision medicine trials disrupted the paradigm of randomized controlled trials in large populations. Patient selection may be based on molecular alterations rather than on primary tumor location. In small patient populations, the growth modulation index (GMI) has been developed to evaluate treatment efficacy by using each patient as its own control. The FFCD 0307 randomized phase III trial compared two sequences of chemotherapy in advanced gastric cancer, which represents a unique opportunity to evaluate the relevance of the GMI. In the FFCD 0307 trial, patients with advanced gastric cancer were randomized between two chemotherapy sequences [ECX followed by FOLFIRI at disease progression (arm A) versus FOLFIRI followed by ECX (arm B)]. GMI was defined as the ratio of the progression-free survival on second treatment (PFS2) to the time to progression on first treatment (TTP1). Sequence benefit was defined as a GMI exceeding 1.3 (GMI-high). GMI was correlated with overall survival (OS). OS1 and OS2 were measured from first randomization and second-line failure to death. Four hundred and sixteen patients were randomized (209 in arm A, 207 in arm B). One hundred and seventy-five patients (42%) received the two sequences and were assessable for GMI (97 in arm A, 79 in arm B). The median GMI was higher in arm A than in arm B (0.62 versus 0.47, P = 0.04). Patients with a high GMI had a longer OS1 (median 14.9 versus 11.5 months, NS). Median OS2 was doubled in the GMI-high group (3.4 versus 1.6 months, NS). GMI analyses suggest that ECX followed by FOLFIRI might represent a better therapeutic strategy than FOLFIRI followed by ECX. High GMI was associated with prolonged survival.
Sections du résumé
BACKGROUND
Precision medicine trials disrupted the paradigm of randomized controlled trials in large populations. Patient selection may be based on molecular alterations rather than on primary tumor location. In small patient populations, the growth modulation index (GMI) has been developed to evaluate treatment efficacy by using each patient as its own control. The FFCD 0307 randomized phase III trial compared two sequences of chemotherapy in advanced gastric cancer, which represents a unique opportunity to evaluate the relevance of the GMI.
PATIENTS AND METHODS
In the FFCD 0307 trial, patients with advanced gastric cancer were randomized between two chemotherapy sequences [ECX followed by FOLFIRI at disease progression (arm A) versus FOLFIRI followed by ECX (arm B)]. GMI was defined as the ratio of the progression-free survival on second treatment (PFS2) to the time to progression on first treatment (TTP1). Sequence benefit was defined as a GMI exceeding 1.3 (GMI-high). GMI was correlated with overall survival (OS). OS1 and OS2 were measured from first randomization and second-line failure to death.
RESULTS
Four hundred and sixteen patients were randomized (209 in arm A, 207 in arm B). One hundred and seventy-five patients (42%) received the two sequences and were assessable for GMI (97 in arm A, 79 in arm B). The median GMI was higher in arm A than in arm B (0.62 versus 0.47, P = 0.04). Patients with a high GMI had a longer OS1 (median 14.9 versus 11.5 months, NS). Median OS2 was doubled in the GMI-high group (3.4 versus 1.6 months, NS).
CONCLUSION
GMI analyses suggest that ECX followed by FOLFIRI might represent a better therapeutic strategy than FOLFIRI followed by ECX. High GMI was associated with prolonged survival.
Identifiants
pubmed: 37542912
pii: S2059-7029(23)00851-7
doi: 10.1016/j.esmoop.2023.101616
pmc: PMC10485393
pii:
doi:
Substances chimiques
Fluorouracil
U3P01618RT
Leucovorin
Q573I9DVLP
Types de publication
Clinical Trial, Phase III
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
101616Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Références
Oncologist. 2014 Oct;19(10):e5-11
pubmed: 25170012
J Clin Oncol. 2016 Aug 20;34(24):2925-34
pubmed: 27247218
J Clin Oncol. 2015 Aug 10;33(23):2563-77
pubmed: 26101248
Br J Cancer. 2012 Feb 28;106(5):854-7
pubmed: 22281665
Nat Med. 2019 May;25(5):744-750
pubmed: 31011206
J Clin Oncol. 2010 Nov 20;28(33):4877-83
pubmed: 20921468
Contemp Clin Trials. 2011 Jan;32(1):99-107
pubmed: 20920605
J Clin Oncol. 2004 Jun 15;22(12):2395-403
pubmed: 15197201
Ann Oncol. 2015 Aug;26(8):1547-73
pubmed: 26026162
Ann Oncol. 2017 Mar 1;28(3):590-596
pubmed: 27993804
Drugs. 2019 Feb;79(2):201-206
pubmed: 30635837
Chin Clin Oncol. 2021 Jun;10(3):23
pubmed: 33977726
J Clin Oncol. 2014 Nov 1;32(31):3520-6
pubmed: 25287828
ESMO Open. 2021 Apr;6(2):100072
pubmed: 33676294
Lancet Oncol. 2020 Feb;21(2):271-282
pubmed: 31838007
Nat Med. 2019 May;25(5):751-758
pubmed: 31011205
J Clin Oncol. 2012 May 1;30(13):1513-8
pubmed: 22412140
Prz Gastroenterol. 2019;14(1):26-38
pubmed: 30944675
Cancer Discov. 2017 Jun;7(6):586-595
pubmed: 28365644
ESMO Open. 2022 Feb;7(1):100366
pubmed: 34979424
Cancers (Basel). 2021 Jun 02;13(11):
pubmed: 34199382