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Comment
. 2021 Dec 1;27(23):6314-6322.
doi: 10.1158/1078-0432.CCR-21-1789. Epub 2021 Sep 27.

Randomized Phase II Study of PARP Inhibitor ABT-888 (Veliparib) with Modified FOLFIRI versus FOLFIRI as Second-line Treatment of Metastatic Pancreatic Cancer: SWOG S1513

E Gabriela Chiorean  1   2 , Katherine A Guthrie  2   3 , Philip A Philip  4 , Elizabeth M Swisher  5 , Florencia Jalikis  5   6 , Michael J Pishvaian  7   8 , Jordan Berlin  6 , Marcus S Noel  7 , Jennifer M Suga  9 , Ignacio Garrido-Laguna  10 , Dana Backlund Cardin  6 , Marc R Radke  5 , Mai Duong  2   3 , Shay Bellasea  2   3 , Andrew M Lowy  11 , Howard S Hochster  12
Affiliations
Comment

Randomized Phase II Study of PARP Inhibitor ABT-888 (Veliparib) with Modified FOLFIRI versus FOLFIRI as Second-line Treatment of Metastatic Pancreatic Cancer: SWOG S1513

E Gabriela Chiorean et al. Clin Cancer Res. .

Abstract

Purpose: PARP inhibitors synergize with topoisomerase inhibitors, and veliparib plus modified (m) FOLFIRI (no 5-FU bolus) had preliminary activity in metastatic pancreatic cancers. This study evaluated the safety and efficacy of second-line treatment with veliparib and mFOLFIRI versus FOLFIRI (control) for metastatic pancreatic cancer.

Patients and methods: This randomized phase II clinical trial led by the SWOG Cancer Research Network enrolled patients between September 1, 2016 and December 13, 2017. The median follow-up was 9 months (IQR 1-27). BRCA1/2 and homologous recombination DNA damage repair (HR-DDR) genetic defects were tested in blood and tumor biopsies. Patients received veliparib 200 mg twice daily, days 1-7 with mFOLFIRI days 3-5, or FOLFIRI in 14-day cycles.

Results: After 123 of planned 143 patients were accrued, an interim futility analysis indicated that the veliparib arm was unlikely to be superior to control, and the study was halted. Median overall survival (OS) was 5.4 versus 6.5 months (HR, 1.23; P = 0.28), and median progression-free survival (PFS) was 2.1 versus 2.9 months (HR, 1.39; P = 0.09) with veliparib versus control. Grade 3/4 toxicities were more common with veliparib (69% vs. 58%, P = 0.23). For cancers with HR-DDR defects versus wild-type, median PFS and OS were 7.3 versus 2.5 months (P = 0.05) and 10.1 versus 5.9 months (P = 0.17), respectively, with FOLFIRI, and 2.0 versus 2.1 months (P = 0.62) and 7.4 versus 5.1 months (P = 0.10), respectively, with veliparib plus mFOLFIRI.

Conclusions: Veliparib plus mFOLFIRI did not improve survival for metastatic pancreatic cancer. FOLFIRI should be further studied in pancreatic cancers with HR-DDR defects.

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Conflict of interest statement

Conflict of Interest Statement:

E.G. Chiorean: consulting/advisory: Astra Zeneca, Bayer, Celgene, Eisai, Ipsen, Legend, Noxxon, Pfizer, Seattle Genetics, Sobi; research grants: NCI/NIH, Boehringer-Ingelheim, Bristol Meyers Squibb, Celgene, Clovis, Corcept, Fibrogen, Halozyme, Incyte, Lilly, MacroGenics, Merck, Halozyme, Rafael, Roche, Stemline.

K.A. Guthrie: no conflicts

P.A. Philip: consulting/advisory: Ipsen, Trisalus, AbbVie, Celgene, Astra Zeneca, Bayer, Merck, Merus; research grants: Celgene, Lilly, Ipsen, Bayer, QED, Incyte, Roche, Rafael, AAA, Novartis, Novocure

E.M. Swisher: no conflicts

F. Jalikis: no conflicts

J.M. Suga: consulting/advisory: Strata Oncology; research funding: NCI NCORP

M.J. Pishvaian: consulting/advisory: Caris Life Sciences, Celgene, Halozyme, Merck, Merrimack, Perthera, Sirtex Medical, AstraZeneca/MedImmune, RenovoR; stock in Perthera; research grants: ARMO BioSciences, Bavarian Nordic, Bayer, Bristol-Myers Squibb, Calithera Biosciences, Celgene, Celldex, Curegenix, Fibrogen, Genentech, Gilead Sciences, GlaxoSmithKline, Halozyme, Karyopharm Therapeutics, MedImmune, Merck, Novartis, Regeneron, Pfizer, Pharmacyclics, Tesaro, Pancreatic Cancer Action Network

J. Berlin: consulting/advisory: Erytech, Gritstone, Celgene, AbbVie, Symphogen, EMD/Serono, Astra Zeneca, Armo, FivePrime, Eisai, Elevar, Bayer, Seattle Genetics, QED, Ipsen, Clovis; DSMB: Astra Zeneca, Novocure, PanCan, NCI; research grants: Symphogen, Abbvie, Immunomedics, Gilead, Boston Biomedical, MacroGenics, Pfizer, Novartis, Roche, Lilly, EMD/Serono, Loxo, PsiOxus, FivePrime, Bayer, Taiho

M.S. Noel: consulting/advisory: Celgene, Ipsen

I. Garrido-Laguna: consulting/advisory: Array Biopharma; research grants: Novartis, Ignyta, Halozyme, Bayer, Bristol Meyers Squibb, Pfizer, NewLink Genetics, MedImmune, Lilly, Incyte, GlaxoSmithKline, OncoMed, ARMO, Glennmark

D. Backlund Cardin: no conflicts

M.R. Radke: no conflicts

M. Duong: no conflicts

S. Bellasea: no conflicts

A.M. Lowy: consulting/advisory: Fount/Kinnate Therapeutics, Bexxion, Pfizer, Merck, Rafael

H.S. Hochster: consulting/advisory: Bayer, Genentech, Amgen, Exelixis

Figures

Figure 1:
Figure 1:
CONSORT Flow Diagram Random assignment and patient disposition in each treatment arm Abbreviations: FOLFIRI, folinic acid, 5-fluorouracil (5-FU), irinotecan; mFOLFIRI modified FOLFIRI (no 5-FU bolus)
Figure 2:
Figure 2:
Kaplan-Meier Curves of A) Overall Survival and B) Progression-Free Survival by Treatment Arm Abbreviations: FOLFIRI, folinic acid, 5-fluorouracil (5-FU), irinotecan; mFOLFIRI modified FOLFIRI (no 5-FU bolus); HR, hazard ratio
Figure 2:
Figure 2:
Kaplan-Meier Curves of A) Overall Survival and B) Progression-Free Survival by Treatment Arm Abbreviations: FOLFIRI, folinic acid, 5-fluorouracil (5-FU), irinotecan; mFOLFIRI modified FOLFIRI (no 5-FU bolus); HR, hazard ratio
Figure 3:
Figure 3:
A) Overall Survival with FOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; B) Overall Survival with Veliparib and mFOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; C) Progression-Free Survival with FOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; D) Progression-Free Survival with Veliparib and mFOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; E) Best Response and Survival for Patients with HR-DDR Gene Defects Abbreviations: HR, hazard ratio; HR-DDR, homologous recombination DNA damage repair; OS, overall survival; PFS, progression-free survival
Figure 3:
Figure 3:
A) Overall Survival with FOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; B) Overall Survival with Veliparib and mFOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; C) Progression-Free Survival with FOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; D) Progression-Free Survival with Veliparib and mFOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; E) Best Response and Survival for Patients with HR-DDR Gene Defects Abbreviations: HR, hazard ratio; HR-DDR, homologous recombination DNA damage repair; OS, overall survival; PFS, progression-free survival
Figure 3:
Figure 3:
A) Overall Survival with FOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; B) Overall Survival with Veliparib and mFOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; C) Progression-Free Survival with FOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; D) Progression-Free Survival with Veliparib and mFOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; E) Best Response and Survival for Patients with HR-DDR Gene Defects Abbreviations: HR, hazard ratio; HR-DDR, homologous recombination DNA damage repair; OS, overall survival; PFS, progression-free survival
Figure 3:
Figure 3:
A) Overall Survival with FOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; B) Overall Survival with Veliparib and mFOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; C) Progression-Free Survival with FOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; D) Progression-Free Survival with Veliparib and mFOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; E) Best Response and Survival for Patients with HR-DDR Gene Defects Abbreviations: HR, hazard ratio; HR-DDR, homologous recombination DNA damage repair; OS, overall survival; PFS, progression-free survival
Figure 3:
Figure 3:
A) Overall Survival with FOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; B) Overall Survival with Veliparib and mFOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; C) Progression-Free Survival with FOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; D) Progression-Free Survival with Veliparib and mFOLFIRI for Cancers with HR-DDR Gene Defects vs Wild Type; E) Best Response and Survival for Patients with HR-DDR Gene Defects Abbreviations: HR, hazard ratio; HR-DDR, homologous recombination DNA damage repair; OS, overall survival; PFS, progression-free survival
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Comment on

  • Selected Articles from This Issue.
    [No authors listed] [No authors listed] Clin Cancer Res. 2021 Dec 1;27(23):6279. doi: 10.1158/1078-0432.CCR-27-23-HI. Clin Cancer Res. 2021. PMID: 34853073 No abstract available.

References

    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics 2021. CA Cancer J Clin 2021; 71: 7–33. - PubMed
    1. Neuzillet C, Hentic O, Rousseau B, Rebours V, Bengrine-Lefèvre L, Bonnetain F, et al. FOLFIRI regimen in metastatic pancreatic adenocarcinoma resistant to gemcitabine and platinum-salts. World J Gastroenterol 2012; 18: 4533–41. - PMC - PubMed
    1. Wang-Gillam A, Hubner RA, Siveke JT, Von Hoff DD, Belanger B, de Jong FA, et al. NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall survival analysis and characteristics of long-term survivors. Eur J Cancer 2019; 108: 78–87. - PubMed
    1. Holter S, Borgida A, Dodd A, Grant R, Semotiuk K, Hedley D, et al. Germline BRCA mutations in a large clinic-based cohort of patients with pancreatic adenocarcinoma. J Clin Oncol 2015; 33: 3124–9. - PubMed
    1. Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, et al. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 2015; 518: 495–501. - PMC - PubMed

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