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A randomized phase II trial of nab-paclitaxel and gemcitabine with tarextumab or placebo in patients with untreated metastatic pancreatic cancer.

Publication ,  Journal Article
Hu, ZI; Bendell, JC; Bullock, A; LoConte, NK; Hatoum, H; Ritch, P; Hool, H; Leach, JW; Sanchez, J; Sohal, DPS; Strickler, J; Patel, R; Yu, KH ...
Published in: Cancer Med
September 2019

PURPOSE: Notch signaling dysregulation is implicated in the development of pancreatic adenocarcinoma (PDAC). Tarextumab is a fully human IgG2 antibody that inhibits Notch2/3 receptors. PATIENTS AND METHODS: Aphase 2, randomized, placebo-controlled, multicenter trial evaluated the activity of tarextumab in combination with nab-paclitaxel and gemcitabine in patients with metastatic PDAC. Patients were stratified based on ECOG performance score and Ca 19-9 level and randomized 1:1 to nab-paclitaxel, gemcitabine with either tarextumab or placebo. Based on preclinical and phase Ib results suggesting a positive correlation between Notch3 gene expression and tarextumab anti-tumor activity, patients were also divided into subgroups of low, intermediate, and high Notch3 gene expression. Primary endpoint was overall survival (OS) in all and in patients with the three Notch3 gene expression subgroups (≥25th, ≥50% and ≥75% percentiles); secondary end points included progression-free survival (PFS), 12-month OS, overall response rate (ORR), and safety and biomarker investigation. RESULTS: Median OS was 6.4 months in the tarextumab group vs 7.9 months in the placebo group (HR = 1.34 [95% CI = 0.95, 1.89], P = .0985). No difference observed in OS in the Notch3 gene expression subgroups. PFS in the tarextumab-treated group (3.7 months) was significantly shorter compared with the placebo group (5.5 months) (hazard ratio was 1.43 [95% CI = 1.01, 2.01]; P = .04). Grade 3 diarrhea and thrombocytopenia were more common in the tarextumab group. CONCLUSIONS: The addition of tarextumab to nab-paclitaxel and gemcitabine did not improve OS, PFS, or ORR in first-line metastatic PDAC, and PFS was specifically statistically worse in the tarextumab-treated patients. CLINICAL TRIAL REGISTRY NO: NCT01647828.

Duke Scholars

Published In

Cancer Med

DOI

EISSN

2045-7634

Publication Date

September 2019

Volume

8

Issue

11

Start / End Page

5148 / 5157

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Receptor, Notch3
  • Receptor, Notch2
  • Prognosis
  • Pancreatic Neoplasms
  • Paclitaxel
  • Molecular Targeted Therapy
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate
 

Citation

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MLA
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Hu, Z. I., Bendell, J. C., Bullock, A., LoConte, N. K., Hatoum, H., Ritch, P., … O’Reilly, E. M. (2019). A randomized phase II trial of nab-paclitaxel and gemcitabine with tarextumab or placebo in patients with untreated metastatic pancreatic cancer. Cancer Med, 8(11), 5148–5157. https://doi.org/10.1002/cam4.2425
Hu, Zishuo Ian, Johanna C. Bendell, Andrea Bullock, Noelle K. LoConte, Hassan Hatoum, Paul Ritch, Hugo Hool, et al. “A randomized phase II trial of nab-paclitaxel and gemcitabine with tarextumab or placebo in patients with untreated metastatic pancreatic cancer.Cancer Med 8, no. 11 (September 2019): 5148–57. https://doi.org/10.1002/cam4.2425.
Hu ZI, Bendell JC, Bullock A, LoConte NK, Hatoum H, Ritch P, et al. A randomized phase II trial of nab-paclitaxel and gemcitabine with tarextumab or placebo in patients with untreated metastatic pancreatic cancer. Cancer Med. 2019 Sep;8(11):5148–57.
Hu, Zishuo Ian, et al. “A randomized phase II trial of nab-paclitaxel and gemcitabine with tarextumab or placebo in patients with untreated metastatic pancreatic cancer.Cancer Med, vol. 8, no. 11, Sept. 2019, pp. 5148–57. Pubmed, doi:10.1002/cam4.2425.
Hu ZI, Bendell JC, Bullock A, LoConte NK, Hatoum H, Ritch P, Hool H, Leach JW, Sanchez J, Sohal DPS, Strickler J, Patel R, Wang-Gillam A, Firdaus I, Yu KH, Kapoun AM, Holmgren E, Zhou L, Dupont J, Picozzi V, Sahai V, O’Reilly EM. A randomized phase II trial of nab-paclitaxel and gemcitabine with tarextumab or placebo in patients with untreated metastatic pancreatic cancer. Cancer Med. 2019 Sep;8(11):5148–5157.
Journal cover image

Published In

Cancer Med

DOI

EISSN

2045-7634

Publication Date

September 2019

Volume

8

Issue

11

Start / End Page

5148 / 5157

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Receptor, Notch3
  • Receptor, Notch2
  • Prognosis
  • Pancreatic Neoplasms
  • Paclitaxel
  • Molecular Targeted Therapy
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate