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Phase Ib study of duligotuzumab (MEHD7945A) plus cisplatin/5-fluorouracil or carboplatin/paclitaxel for first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck

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Jimeno, Antonio Machiels, Jean-Pascal [UCL] Wirth, Lori Specenier, Pol Seiwert, Tanguy Y Mardjuadi, Feby [UCL] Clement, Paul M

BACKGROUND: This open-label, multicenter, phase Ib study assessed the safety and preliminary activity of duligotuzumab, a dual-action antibody that blocks ligand binding to human epidermal growth factor receptor 3 (HER3) and epidermal growth factor receptor, in combination with chemotherapy, in the first-line treatment of patients with recurrent/metastatic squamous cell cancer of the head and neck. METHODS: On day 1, duligotuzumab at a dose of 1650 mg intravenously was combined with cisplatin at a dose of 100 mg/m2 and 5-fluorouracil at a dose of 1000 mg/m2 /day on days 1 to 4 in treatment arm A, or carboplatin (area under the curve, 6 mg/mL/min) and paclitaxel (at a dose of 200 mg/m2 ) in treatment arm B. Up to 6 cycles (21 days/cycle) were followed by duligotuzumab maintenance until disease progression or intolerable toxicity occurred. RESULTS: Nine patients in arm A and 15 patients in arm B received a median of 6 cycles of chemotherapy, and a median of 11 cycles (arm A) and 9 cycles (arm B) of duligotuzumab. Dose-limiting toxicities occurred in 3 patients in arm A and 1 patient in arm B. Grade ≥ 3 treatment-related adverse events (graded according to graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]) in ≥ 3 patients were neutropenia (5 patients), hypokalemia (4 patients), dehydration (3 patients), anemia (3 patients), and diarrhea (3 patients) in arm A, and neutropenia (8 patients), anemia (5 patients), febrile neutropenia (4 patients), leukopenia (3 patients), thrombocytopenia (3 patients), and hypomagnesemia (3 patients) in arm B. The chemotherapy dose was reduced in 19 of 24 patients. Sixteen patients (67%) demonstrated objective responses regardless of human papillomavirus status or neuregulin 1 (NRG1) mRNA expression (arm A: 2 confirmed complete responses and 4 confirmed partial responses; arm B: 2 confirmed complete responses and 8 confirmed partial responses). CONCLUSIONS: Duligotuzumab in combination with cisplatin/5-fluorouracil or carboplatin/paclitaxel demonstrated encouraging activity in patients with recurrent/metastatic squamous cell cancer of the head and neck; an association with increased frequency and severity of select adverse events relative to historical data was suggestive of the potentiation of chemotherapy-related adverse events. Cancer 2016;122:3803-3811. © 2016 American Cancer Society.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2016
Language Anglais
Journal information "Cancer" - Vol. 122, no.24, p. 3803-3811 (2016)
Peer reviewed yes
Publisher JohnWiley & Sons, Inc. ((United States) Hoboken, NJ)
issn 0008-543X
e-issn 1097-0142
Publication status Publié
Affiliations UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie
UCL - (SLuc) Unité d'oncologie médicale
Keywords Antibody ; Clinical trial ; Duligotuzumab ; Epidermal Growth Factor Receptor (EGFR) ; Human Epidermal growth factor Receptor 3 (HER3)
Links
  1. Gibson Michael K., Li Yi, Murphy Barbara, Hussain Maha H.A., DeConti Ronald C., Ensley John, Forastiere Arlene A., Randomized Phase III Evaluation of Cisplatin Plus Fluorouracil Versus Cisplatin Plus Paclitaxel in Advanced Head and Neck Cancer (E1395): An Intergroup Trial of the Eastern Cooperative Oncology Group, 10.1200/jco.2005.01.057
  2. Vermorken Jan B., Mesia Ricard, Rivera Fernando, Remenar Eva, Kawecki Andrzej, Rottey Sylvie, Erfan Jozsef, Zabolotnyy Dmytro, Kienzer Heinz-Roland, Cupissol Didier, Peyrade Frederic, Benasso Marco, Vynnychenko Ihor, De Raucourt Dominique, Bokemeyer Carsten, Schueler Armin, Amellal Nadia, Hitt Ricardo, Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer, 10.1056/nejmoa0802656
  3. Normanno Nicola, De Luca Antonella, Bianco Caterina, Strizzi Luigi, Mancino Mario, Maiello Monica R., Carotenuto Adele, De Feo Gianfranco, Caponigro Francesco, Salomon David S., Epidermal growth factor receptor (EGFR) signaling in cancer, 10.1016/j.gene.2005.10.018
  4. Kalyankrishna Shailaja, Grandis Jennifer R., Epidermal Growth Factor Receptor Biology in Head and Neck Cancer, 10.1200/jco.2005.04.8306
  5. Grandis Jennifer Rubin, Melhem Mona F., Gooding William E., Day Roger, Holst Valerie A., Wagener Marilyn M., Drenning Stephanie D., Tweardy David J., Levels of TGF-α and EGFR Protein in Head and Neck Squamous Cell Carcinoma and Patient Survival, 10.1093/jnci/90.11.824
  6. Chung Christine H., Ely Kim, McGavran Loris, Varella-Garcia Marileila, Parker Joel, Parker Natalie, Jarrett Carolyn, Carter Jesse, Murphy Barbara A., Netterville James, Burkey Brian B., Sinard Robert, Cmelak Anthony, Levy Shawn, Yarbrough Wendell G., Slebos Robbert J.C., Hirsch Fred R., Increased Epidermal Growth Factor Receptor Gene Copy Number Is Associated With Poor Prognosis in Head and Neck Squamous Cell Carcinomas, 10.1200/jco.2006.07.2587
  7. Temam Stephane, Kawaguchi Hidetoshi, El-Naggar Adel K., Jelinek Jaroslav, Tang Hongli, Liu Diane D., Lang Wenhua, Issa Jean-Pierre, Lee J. Jack, Mao Li, Epidermal Growth Factor Receptor Copy Number Alterations Correlate With Poor Clinical Outcome in Patients With Head and Neck Squamous Cancer, 10.1200/jco.2006.06.6605
  8. Ang, Cancer Res, 62, 7350 (2002)
  9. Vermorken Jan B., Trigo José, Hitt Ricardo, Koralewski Piotr, Diaz-Rubio Eduardo, Rolland Frédéric, Knecht Rainald, Amellal Nadia, Schueler Armin, Baselga José, Open-Label, Uncontrolled, Multicenter Phase II Study to Evaluate the Efficacy and Toxicity of Cetuximab As a Single Agent in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Who Failed to Respond to Platinum-Based Therapy, 10.1200/jco.2006.06.7447
  10. Machiels Jean-Pascal H, Haddad Robert I, Fayette Jérôme, Licitra Lisa F, Tahara Makoto, Vermorken Jan B, Clement Paul M, Gauler Thomas, Cupissol Didier, Grau Juan José, Guigay Joël, Caponigro Francesco, de Castro Gilberto, de Souza Viana Luciano, Keilholz Ulrich, del Campo Joseph M, Cong Xiuyu Julie, Ehrnrooth Eva, Cohen Ezra E W, Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial, 10.1016/s1470-2045(15)70124-5
  11. Cohen E. E.W., Phase II Trial of Gefitinib 250 mg Daily in Patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck, 10.1158/1078-0432.ccr-05-1247
  12. Kirby, Br J Cancer, 94, 631 (2006)
  13. Soulieres Denis, Senzer Neil N., Vokes Everett E., Hidalgo Manuel, Agarwala Sanjiv S., Siu Lillian L., Multicenter Phase II Study of Erlotinib, an Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck, 10.1200/jco.2004.06.075
  14. Stewart J. Simon W., Cohen Ezra E.W., Licitra Lisa, Van Herpen Carla M.L., Khorprasert Chonlakiet, Soulieres Denis, Vodvarka Pavel, Rischin Danny, Garin Avgust M., Hirsch Fred R., Varella-Garcia Marileila, Ghiorghiu Serban, Hargreaves Laura, Armour Alison, Speake Georgina, Swaisland Alan, Vokes Everett E., Phase III Study of Gefitinib Compared With Intravenous Methotrexate for Recurrent Squamous Cell Carcinoma of the Head and Neck, 10.1200/jco.2008.17.0530
  15. Burtness Barbara, Goldwasser Meredith A., Flood William, Mattar Bassam, Forastiere Arlene A., Phase III Randomized Trial of Cisplatin Plus Placebo Compared With Cisplatin Plus Cetuximab in Metastatic/Recurrent Head and Neck Cancer: An Eastern Cooperative Oncology Group Study, 10.1200/jco.2005.02.4646
  16. Wilson Timothy R., Lee Diana Y., Berry Leanne, Shames David S., Settleman Jeff, Neuregulin-1-Mediated Autocrine Signaling Underlies Sensitivity to HER2 Kinase Inhibitors in a Subset of Human Cancers, 10.1016/j.ccr.2011.07.011
  17. Shames David S., Carbon Juliet, Walter Kim, Jubb Adrian M., Kozlowski Cleopatra, Januario Tom, An Do, Fu Ling, Xiao Yuanyuan, Raja Rajiv, Jiang Brittany, Malekafzali Ashi, Stern Howard, Settleman Jeff, Wilson Timothy R., Hampton Garret M., Yauch Robert L., Pirzkall Andrea, Amler Lukas C., High Heregulin Expression Is Associated with Activated HER3 and May Define an Actionable Biomarker in Patients with Squamous Cell Carcinomas of the Head and Neck, 10.1371/journal.pone.0056765
  18. Sliwkowski, J Biol Chem, 269, 14661 (1994)
  19. Bostrom J., Yu S.-F., Kan D., Appleton B. A., Lee C. V., Billeci K., Man W., Peale F., Ross S., Wiesmann C., Fuh G., Variants of the Antibody Herceptin That Interact with HER2 and VEGF at the Antigen Binding Site, 10.1126/science.1165480
  20. Schaefer Gabriele, Haber Lauric, Crocker Lisa M., Shia Steven, Shao Lily, Dowbenko Donald, Totpal Klara, Wong Anne, Lee Chingwei V., Stawicki Scott, Clark Robyn, Fields Carter, Lewis Phillips Gail D., Prell Rodney A., Danilenko Dimitry M., Franke Yvonne, Stephan Jean-Philippe, Hwang Jiyoung, Wu Yan, Bostrom Jenny, Sliwkowski Mark X., Fuh Germaine, Eigenbrot Charles, A Two-in-One Antibody against HER3 and EGFR Has Superior Inhibitory Activity Compared with Monospecific Antibodies, 10.1016/j.ccr.2011.09.003
  21. Huang Shyhmin, Li Chunrong, Sliwkowski Mark X., Harari Paul M., Abstract 637: MEHD7945A, an EGFR/ErbB3 dual specific antibody, overcomes acquired resistance to EGFR inhibitors in head and neck and lung tumors, 10.1158/1538-7445.am2011-637
  22. Hegde G. V., de la Cruz C. C., Chiu C., Alag N., Schaefer G., Crocker L., Ross S., Goldenberg D., Merchant M., Tien J., Shao L., Roth L., Tsai S.-P., Stawicki S., Jin Z., Wyatt S. K., Carano R. A. D., Zheng Y., Sweet-Cordero E. A., Wu Y., Jackson E. L., Blocking NRG1 and Other Ligand-Mediated Her4 Signaling Enhances the Magnitude and Duration of the Chemotherapeutic Response of Non-Small Cell Lung Cancer, 10.1126/scitranslmed.3004438
  23. Juric D., Dienstmann R., Cervantes A., Hidalgo M., Messersmith W., Blumenschein G. R., Tabernero J., Roda D., Calles A., Jimeno A., Wang X., Bohorquez S. S., Leddy C., Littman C., Kapp A. V., Shames D. S., Penuel E., Amler L. C., Pirzkall A., Baselga J., Safety and Pharmacokinetics/Pharmacodynamics of the First-in-Class Dual Action HER3/EGFR Antibody MEHD7945A in Locally Advanced or Metastatic Epithelial Tumors, 10.1158/1078-0432.ccr-14-2412
  24. Eisenhauer E.A., Therasse P., Bogaerts J., Schwartz L.H., Sargent D., Ford R., Dancey J., Arbuck S., Gwyther S., Mooney M., Rubinstein L., Shankar L., Dodd L., Kaplan R., Lacombe D., Verweij J., New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1), 10.1016/j.ejca.2008.10.026
  25. Hill A Findlay M Burge M Randomized phase II study of duligotuzumab + FOLFIRI vs cetuximab + FOLFIRI in 2nd-line patients with KRAS wild-type metastatic colorectal cancer
  26. Thiberville Luc, Compagnon Patricia, Moore Nicholas, Bastian Gerard, Richard Marie-Odile, Hellot Marie-France, Vincent Colette, Kannass M. M., Dominique Stephane, Thuillez Christian, Nouvet Georges, Plasma 5-fluorouracil and ?-fluoro-?-alanin accumulation in lung cancer patients treated with continuous infusion of cisplatin and 5-fluorouracil, 10.1007/bf00686286
  27. Aisner, Semin Oncol, 22, 17 (1995)
  28. Fayette J., Wirth L.J., Oprean C., Hitt R., Udrea A., Jimeno A., Rischin D., Nutting C., Harari P., Cso˝szi T., Cernea D., Wang X., Kapp A., Anderson M., Penuel E., McCall B., Pirzkall A., Vermorken J.B., 986ORANDOMIZED PHASE II STUDY OF MEHD7945A (MEHD) VS CETUXIMAB (CET) IN >= 2ND-LINE RECURRENT/METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD & NECK (RMSCCHN) PROGRESSIVE ON/AFTER PLATINUM-BASED CHEMOTHERAPY (PTCT), 10.1093/annonc/mdu340.1
  29. D'Souza Gypsyamber, Dempsey Amanda, The role of HPV in head and neck cancer and review of the HPV vaccine, 10.1016/j.ypmed.2011.08.001
  30. Vergote I., Oaknin A., Baurain J.-F., Ananda S., Wong S., Su X., Wu B., Zhong Z., Warner D., Casado A., A phase 1b, open-label study of trebananib in combination with paclitaxel and carboplatin in patients with ovarian cancer receiving interval or primary debulking surgery, 10.1016/j.ejca.2014.06.010
  31. Brana Irene, Calles Antonio, LoRusso Patricia M., Yee Lorrin K., Puchalski Thomas A., Seetharam Shobha, Zhong Bob, de Boer Carla J., Tabernero Josep, Calvo Emiliano, Carlumab, an anti-C-C chemokine ligand 2 monoclonal antibody, in combination with four chemotherapy regimens for the treatment of patients with solid tumors: an open-label, multicenter phase 1b study, 10.1007/s11523-014-0320-2
  32. Vermorken Jan B, Stöhlmacher-Williams Jan, Davidenko Irina, Licitra Lisa, Winquist Eric, Villanueva Cristian, Foa Paolo, Rottey Sylvie, Skladowski Krzysztof, Tahara Makoto, Pai Vasant R, Faivre Sandrine, Blajman Cesar R, Forastiere Arlene A, Stein Brian N, Oliner Kelly S, Pan Zhiying, Bach Bruce A, Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial, 10.1016/s1470-2045(13)70181-5
  33. Lynch Thomas J., Patel Taral, Dreisbach Luke, McCleod Michael, Heim William J., Hermann Robert C., Paschold Eugene, Iannotti Nicholas O., Dakhil Shaker, Gorton Steven, Pautret Virginie, Weber Martin R., Woytowitz Donald, Cetuximab and First-Line Taxane/Carboplatin Chemotherapy in Advanced Non–Small-Cell Lung Cancer: Results of the Randomized Multicenter Phase III Trial BMS099, 10.1200/jco.2009.21.9618
  34. Sun M., Behrens C., Feng L., Ozburn N., Tang X., Yin G., Komaki R., Varella-Garcia M., Hong W. K., Aldape K. D., Wistuba I. I., HER Family Receptor Abnormalities in Lung Cancer Brain Metastases and Corresponding Primary Tumors, 10.1158/1078-0432.ccr-08-2921
  35. Vermorken J. B., Psyrri A., Mesía R., Peyrade F., Beier F., de Blas B., Celik I., Licitra L., Impact of tumor HPV status on outcome in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck receiving chemotherapy with or without cetuximab: retrospective analysis of the phase III EXTREME trial, 10.1093/annonc/mdt574
Bibliographic reference Jimeno, Antonio ; Machiels, Jean-Pascal ; Wirth, Lori ; Specenier, Pol ; Seiwert, Tanguy Y ; et. al. Phase Ib study of duligotuzumab (MEHD7945A) plus cisplatin/5-fluorouracil or carboplatin/paclitaxel for first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck. In: Cancer, Vol. 122, no.24, p. 3803-3811 (2016)
Permanent URL http://hdl.handle.net/2078.1/182643