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nab-Paclitaxel and cisplatin followed by cisplatin and radiation (Arm 1) and nab-paclitaxel followed by cetuximab and radiation (Arm 2) for locally advanced head and neck squamous-cell carcinoma: a multicenter, non-randomized phase 2 trial

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Abstract

In locally advanced head and neck squamous-cell carcinoma (LA-HNSCC), clinical complete response (cCR) at the primary site, assessed by clinical examination, after induction chemotherapy predicts for a low relapse risk after subsequent chemoradiotherapy. Prior studies showed a cCR rate of 77% with induction nanoparticle albumin-bound (nab)-paclitaxel given with cisplatin and 5-fluorouracil (APF). The primary aims of this non-randomized phase 2 trial were to determine the cCR rate after induction nab-paclitaxel and cisplatin (Arm 1) and after nab-paclitaxel monotherapy (Arm 2). Eligibility required LA-HNSCC, T2-T4 stage classification, and suitable (Arm 1) or unsuitable (Arm 2) candidates for cisplatin. Arm 1 patients received nab-paclitaxel and cisplatin, then cisplatin with radiation. Arm 2 patients received nab-paclitaxel, then cetuximab with radiation. The primary endpoint was cCR after two cycles of induction chemotherapy. Each arm enrolled forty patients. cCR at the primary site occurred in 28 patients (70%) after nab-paclitaxel and cisplatin and in 8 patients (20%) after nab-paclitaxel monotherapy. The overall clinical response rate was 98% after nab-paclitaxel and cisplatin and 90% after nab-paclitaxel monotherapy. In subset analyses, cCR rates by T stage classifications (T2, T3, T4) were 54, 86, and 69% after nab-paclitaxel and cisplatin, and 14, 11, and 26% after nab-paclitaxel. cCR rates by human papillomavirus status (p16 positive oropharynx vs other) were 72 and 64% after nab-paclitaxel and cisplatin and 35 and 9% after nab-paclitaxel. The cCR rate after nab-paclitaxel and cisplatin was similar to APF; however, the cCR rate after nab-paclitaxel monotherapy was lower. The trial was registered at ClinicalTrials.gov NCT02573493 on October 9, 2015.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The Siteman Cancer Center is supported in part by NCI Cancer Center Support (Grant number P30 CA91842). We acknowledge funding from Celgene for this project and the support of Tin Jin Ong MD, Kathy Amiri PhD, Jeff Eskew PhD, Monserrat Valles PhD, Jacqueline Jesse PharmD, and Daniel Read PhD. We thank the patients who participated, the head and neck research team at Washington University, Kim Trinkaus PhD, the Alvin Siteman Cancer Center (Washington University, St Louis, Missouri, USA) and Barnes-Jewish Hospital (St Louis) for use of the Tissue Procurement Center, and the Center for Biomedical Informatics.

Funding

This work was supported in part by Grant funding from Celgene. Clinical trial sponsorship by Celgene and Siteman Cancer Center in part by NCI Cancer Center Support Award Number P30 CA91842.

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Authors and Affiliations

  1. Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA

    Peter Oppelt, Mackenzie Daly, Jason Rich, Randal Paniello, Ryan S. Jackson, Patrik Pipkorn, Hiram Gay, Kevin Palka, Jose Zevallos, Wade Thorstad & Douglas Adkins

  2. Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid, Campus, Box 8056, St. Louis, MO, 63110, USA

    Peter Oppelt, Jessica Ley, Kevin Palka & Douglas Adkins

  3. Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA

    Mackenzie Daly, Hiram Gay & Wade Thorstad

  4. Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, USA

    Jason Rich, Randal Paniello, Ryan S. Jackson, Patrik Pipkorn & Jose Zevallos

  5. Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO, USA

    Jingxia Liu

  6. Division of Oncology, University of Kansas School of Medicine, Kansas, MO, USA

    Prakash Neupane

  7. Sanford Cancer Center, Sanford Health, Sioux Falls, SD, USA

    Steven Powell & William C. Spanos

  8. Sanford Cancer Center, Sanford Health, Fargo, ND, USA

    Mark Gitau

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  1. Peter Oppelt
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by JL, JL, and DA. The first draft of the manuscript was written by JL and DA, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Douglas Adkins.

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Conflict of interest

JL, MD, JR, RP, PP, JL, HG, PN, and MG have no disclosures to report. PO reports personal fees from Bristol Myers, Merck, and Eisai, outside the submitted work. RJ reports personal fees from Intuitive surgical, outside the submitted work. KP reports personal fees from Merck, Genetech, and Boehringer Ingelheim, outside the submitted work. RS reports consulting support from Bristol Myers and institutional research support from Merck, Bristol Myers, Pfizer, Vyriad, Incyte, Genentech, Actuate, and Novartis, outside the submitted work. WS reports consulting support from Bristol Myers and Regeneron, outside the submitted work. JZ reports personal fees from Summit Biolabs, Inc, outside the submitted work. WT reports other from Elekta, Inc (wife is employee. Radiotherapy hardware and software company. However, the department does not use those products). DA reports research funding from Celgene for the submitted work and consulting or scientific advisory board support from Pfizer, Eli Lilly, Merck, Celgene, Cue Biopharma, and institutional research support from Pfizer, Eli Lilly, Merck, Celgene/BMS, Novartis, AstraZeneca, Atara Bio, Blueprint Medicine, Celldex, Enzychem, Kura, Exelixis, Innate, Sensei, and Matrix Biomed, outside the submitted work.

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. The study was reviewed and approved by the Washington University School of Medicine Internal Review Board, St. Louis, Missouri. Patients signed informed consent regarding publishing their data.

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Oppelt, P., Ley, J., Daly, M. et al. nab-Paclitaxel and cisplatin followed by cisplatin and radiation (Arm 1) and nab-paclitaxel followed by cetuximab and radiation (Arm 2) for locally advanced head and neck squamous-cell carcinoma: a multicenter, non-randomized phase 2 trial. Med Oncol 38, 35 (2021). https://doi.org/10.1007/s12032-021-01479-w

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