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A phase 1b study of erlotinib in combination with gemcitabine and nab-paclitaxel in patients with previously untreated advanced pancreatic cancer: an Academic Oncology GI Cancer Consortium study

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Abstract

Purpose

Addition of either nab-paclitaxel or erlotinib to gemcitabine to treat advanced pancreatic cancer has demonstrated overall survival benefit. This study was conducted to evaluate the tolerability and safety of combining all three drugs and assess preliminary evidence of efficacy.

Methods

In this open-label, phase 1b study, patients with previously untreated, advanced pancreatic cancer were treated in 28-day cycles with intravenous gemcitabine/nab-paclitaxel on days 1, 8, and 15, and once daily oral erlotinib. A standard “3 + 3” design was used. Dose level 1 (DL1) for gemcitabine (mg/m2)/nab-paclitaxel (mg/m2)/erlotinib (mg) was 1000/125/100, respectively, with de-escalation to DL−1 (1000/100/100), DL−2b (1000/75/100), and DL−3 (1000/75/75). The maximum tolerated dose (MTD) was defined by occurrence of dose-limiting toxicity (DLT) in ≤1 of six patients within the first cycle. Efficacy was assessed with CT scans performed at two-cycle intervals.

Results

Nineteen patients were enrolled. DLTs occurred in two patients at DL1, three patients at DL−1, two patients at DL−2b, and one patient at DL−3. The MTD for the combination of gemcitabine/nab-paclitaxel/erlotinib was DL−3 (1000/75/75). In analyses of efficacy among 14 evaluable patients, partial responses were observed in four of six patients at DL1, one of two patients at DL−2b, and two of six patients at DL−3.

Conclusion

The addition of erlotinib to gemcitabine and nab-paclitaxel is not tolerable at standard single-agent dosing of all drugs. However, significant clinical activity was noted, even at DL−3. Further study of the combination will need to incorporate reduced dosing.

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Acknowledgments

The authors thank the patients and their families who participated in the study. Medical writing assistance was provided by Tara N. Miller, Ph.D., and Ed Parr, Ph.D., of Envision Scientific Solutions, which was funded by Astellas.

Funding

This study was funded by Astellas.

Author information

Authors and Affiliations

  1. Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111-2497, USA

    Steven J. Cohen

  2. Indiana University Simon Cancer Center, Indianapolis, IN, USA

    Bert H. O’Neil

  3. Vanderbilt-Ingram Cancer Center, Nashville, TN, USA

    Jordan Berlin

  4. Abrazo Community Health Network, Phoenix, AZ, USA

    Patricia Ames

  5. Aptium Oncology, Criterium, Inc., Los Angeles, CA, USA

    Marti McKinley

  6. Novella Clinical, Boulder, CO, USA

    Julie Horan & Patricia M. Catalano

  7. Champions Oncology, Hackensack, NJ, USA

    Angela Davies

  8. University of Colorado School of Medicine, Aurora, CO, USA

    Colin D. Weekes

  9. New York University, New York, NY, USA

    Lawrence Leichman

Authors
  1. Steven J. Cohen
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  2. Bert H. O’Neil
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  3. Jordan Berlin
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  4. Patricia Ames
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  5. Marti McKinley
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  6. Julie Horan
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  7. Patricia M. Catalano
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  8. Angela Davies
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  9. Colin D. Weekes
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  10. Lawrence Leichman
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Corresponding author

Correspondence to Steven J. Cohen.

Ethics declarations

Conflict of interest

Steven Cohen has received personal fees from Celgene Corporation. Jordan Berlin received institutional grants from Astellas related to the study and has received personal fees from Celgene. Julie Horan was an employee of OSI Pharmaceuticals during the conduct of the study. Patricia Catalano is an employee of Novella, who were contracted to perform services related to the study. Angela Davies was an employee of OSI Pharmaceuticals and Astellas during the conduct of the study. Bert O’Neil, Patricia Ames, Marti McKinley, Colin Weekes, and Lawrence Leichman have no conflicts to report.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Dr. Davies was an employee of Astellas when the study was conducted.

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Cohen, S.J., O’Neil, B.H., Berlin, J. et al. A phase 1b study of erlotinib in combination with gemcitabine and nab-paclitaxel in patients with previously untreated advanced pancreatic cancer: an Academic Oncology GI Cancer Consortium study. Cancer Chemother Pharmacol 77, 693–701 (2016). https://doi.org/10.1007/s00280-016-2981-2

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  • DOI: https://doi.org/10.1007/s00280-016-2981-2

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