Phase II study of nimotuzumab (TheraCim-hR3) concurrent with cisplatin/radiotherapy in patients with locally advanced head and neck squamous cell carcinoma
Corresponding Author
Mei-Kim Ang MRCP
Division of Medical Oncology, National Cancer Centre Singapore, Singapore
Correspondence
Mei-Kim Ang, Division of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore 169610, Singapore.
Email: [email protected]
Search for more papers by this authorJose Enrique Montoya MD
Cancer Coordinating Center, The Medical City Clark, Mabalacat, Philippines
Search for more papers by this authorEkkasit Tharavichitkul MD
Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Search for more papers by this authorCindy Lim MSc
Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore
Search for more papers by this authorTerence Tan FRCR
Division of Radiation Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorLan Ying Wang MD
Division of Medical Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorJoseph Wee FRCR
Division of Radiation Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorYoke-Lim Soong FRCR
Division of Radiation Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorKam-Weng Fong FRCR
Division of Radiation Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorQuan Sing Ng MRCP
Division of Medical Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorDaniel Shao-Weng Tan PhD
Division of Medical Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorEng-Huat Tan MRCP
Division of Medical Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorWan-Teck Lim MRCP
Division of Medical Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorCorresponding Author
Mei-Kim Ang MRCP
Division of Medical Oncology, National Cancer Centre Singapore, Singapore
Correspondence
Mei-Kim Ang, Division of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore 169610, Singapore.
Email: [email protected]
Search for more papers by this authorJose Enrique Montoya MD
Cancer Coordinating Center, The Medical City Clark, Mabalacat, Philippines
Search for more papers by this authorEkkasit Tharavichitkul MD
Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Search for more papers by this authorCindy Lim MSc
Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore
Search for more papers by this authorTerence Tan FRCR
Division of Radiation Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorLan Ying Wang MD
Division of Medical Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorJoseph Wee FRCR
Division of Radiation Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorYoke-Lim Soong FRCR
Division of Radiation Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorKam-Weng Fong FRCR
Division of Radiation Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorQuan Sing Ng MRCP
Division of Medical Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorDaniel Shao-Weng Tan PhD
Division of Medical Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorEng-Huat Tan MRCP
Division of Medical Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorWan-Teck Lim MRCP
Division of Medical Oncology, National Cancer Centre Singapore, Singapore
Search for more papers by this authorData previously presented at European Cancer Congress 2013 (Eur J Cancer 2013;49(Suppl 2):pS598–pS758, Abstract 3169).
Abstract
Background
The efficacy of a combination of nimotuzumab, a humanized monoclonal antibody to the epidermal growth factor receptor, with chemoradiation in locally advanced head and neck squamous cell carcinoma (HNSCC) was evaluated in a phase II study.
Methods
Patients with stage III/IV HNSCC received 3-weekly cisplatin 100 mg/m2 for three cycles and weekly nimotuzumab 200 mg for 8 weeks concurrently with radiotherapy. Primary endpoint was best overall response (BOR) and secondary endpoint was progression-free survival (PFS).
Results
Thirty-seven patients were included; the majority were Chinese (76%), male (89%), and had stage IVA/IVB HNSCC (92%). BOR of complete and partial response was seen in 22/37 (59%) and 10/37 (27%) patients, respectively. Median PFS was 17.5 months (95% CI: 11.1–54.5) and 3-year PFS was 40.4% (95% CI: 24.3–55.9). The frequency and type of adverse events observed were similar to standard chemoradiation.
Conclusion
The combination of nimotuzumab with cisplatin and radiotherapy was safe and achieved high response rates in HNSCC.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
REFERENCES
- 1Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136(5): E359-E386.
- 2Maier H, Dietz A, Gewelke U, Heller WD, Weidauer H. Tobacco and alcohol and the risk of head and neck cancer. Clin Investig. 1992; 70(3–4): 320-327.
- 3Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011; 29(32): 4294-4301.
- 4Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer. 2007; 110(7): 1429-1435.
- 5Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003; 349(22): 2091-2098.
- 6Forastiere AA, Zhang Q, Weber RS, et al. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013; 31(7): 845-852.
- 7Lefebvre J-L, Andry G, Chevalier D, et al. Laryngeal preservation with induction chemotherapy for hypopharyngeal squamous cell carcinoma: 10-year results of EORTC trial 24891. Ann Oncol. 2012; 23(10): 2708-2714.
- 8Argiris A, Lefebvre JL. Laryngeal preservation strategies in locally advanced laryngeal and hypopharyngeal cancers. Front Oncol. 2019; 9: 419.
- 9Adelstein DJ, Li Y, Adams GL, et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol. 2003; 21(1): 92-98.
- 10Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010; 363(1): 24-35.
- 11Pignon J-P, le Maître A, Maillard E, Bourhis J, MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009; 92(1): 4-14.
- 12Bossi P, Resteghini C, Paielli N, Licitra L, Pilotti S, Perrone F. Prognostic and predictive value of EGFR in head and neck squamous cell carcinoma. Oncotarget. 2016; 7(45): 74362-77479.
- 13Kalyankrishna S, Grandis JR. Epidermal growth factor receptor biology in head and neck cancer. J Clin Oncol. 2006; 24(17): 2666-2672.
- 14Ciardiello F, Tortora G. EGFR antagonists in cancer treatment. N Engl J Med. 2008; 358(11): 1160-1174.
- 15Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006; 354(6): 567-578.
- 16Petrelli F, Coinu A, Riboldi V, et al. Concomitant platinum-based chemotherapy or cetuximab with radiotherapy for locally advanced head and neck cancer: a systematic review and meta-analysis of published studies. Oral Oncol. 2014; 50(11): 1041-1048.
- 17Gillison ML, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019; 393(10166): 40-50.
- 18Mehanna H, Robinson M, Hartley A, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet. 2019; 393(10166): 51-60.
- 19Siu LL, Waldron JN, Chen BE, et al. Effect of standard radiotherapy with cisplatin vs accelerated radiotherapy with panitumumab in locoregionally advanced squamous cell head and neck carcinoma: a randomized clinical trial. JAMA Oncol. 2017; 3(2): 220-226.
- 20Ang KK, Zhang Q, Rosenthal DI, et al. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol. 2014; 32(27): 2940-2250.
- 21Mesía R, Henke M, Fortin A, et al. Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial. Lancet Oncol. 2015; 16(2): 208-220.
- 22Tao Y, Auperin A, Sire C, et al. Improved outcome by adding concurrent chemotherapy to cetuximab and radiotherapy for locally advanced head and neck carcinomas: results of the GORTEC 2007-01 phase III randomized trial. J Clin Oncol. 2018; 36(31): 3084-3390.
- 23Mazorra Z, Chao L, Lavastida A, et al. Nimotuzumab: beyond the EGFR signaling cascade inhibition. Semin Oncol. 2018; 45(1): 18-26.
- 24Rodríguez MO, Rivero TC, del Castillo BR, et al. Nimotuzumab plus radiotherapy for unresectable squamous-cell carcinoma of the head and neck. Cancer Biol Ther. 2010; 9(5): 343-349.
- 25Rojo F, Gracias E, Villena N, et al. Pharmacodynamic trial of nimotuzumab in unresectable squamous cell carcinoma of the head and neck: a SENDO foundation study. Clin Cancer Res. 2010; 16(8): 2474-2482.
- 26Reddy BKM, Lokesh V, Vidyasagar MS, et al. Nimotuzumab provides survival benefit to patients with inoperable advanced squamous cell carcinoma of the head and neck: a randomized, open-label, phase IIb, 5-year study in Indian patients. Oral Oncol. 2014; 50(5): 498-505.
- 27Patil VM, Noronha V, Joshi A, et al. A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer. Cancer. 2019; 125(18): 3184-3197.
- 28Noronha V, Joshi A, Patil VM, et al. Once-a-week versus once-every-3-weeks cisplatin chemoradiation for locally advanced head and neck cancer: a phase III randomized noninferiority trial. J Clin Oncol. 2018; 36(11): 1064-1072.
- 29Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000; 92(3): 205-216.
- 30Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004; 350(19): 1937-1944.
- 31Kiyota N, Tahara M, Fujii H, et al. Phase II/III trial of post-operative chemoradiotherapy comparing 3-weekly cisplatin with weekly cisplatin in high-risk patients with squamous cell carcinoma of head and neck (JCOG1008). J Clin Oncol. 2020; 38(15): 6502.
- 32Ghi MG, Paccagnella A, Ferrari D, et al. Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer: a phase II-III trial. Ann Oncol. 2017; 28(9): 2206-2212.
- 33Ang S-H, Haaland B, Acharyya S, et al. Interactions between clinical factors, p16, and cyclin-D1 expression and survival outcomes in oropharyngeal and hypopharyngeal squamous cell carcinoma. Head Neck. 2015; 37(11): 1650-1659.
- 34Mazorra Z, Lavastida A, Concha-Benavente F, et al. Nimotuzumab induces NK cell activation, cytotoxicity, dendritic cell maturation and expansion of EGFR-specific T cells in head and neck cancer patients. Front Pharmacol. 2017; 8: 382.
- 35Taberna M, Oliva M, Mesía R. Cetuximab-containing combinations in locally advanced and recurrent or metastatic head and neck squamous cell carcinoma. Front Oncol. 2019; 9: 383.
- 36Ferris RL, Lenz H-J, Trotta AM, et al. Rationale for combination of therapeutic antibodies targeting tumor cells and immune checkpoint receptors: harnessing innate and adaptive immunity through IgG1 isotype immune effector stimulation. Cancer Treat Rev. 2018; 63: 48-60.
- 37Sun XS, Sire C, Tao Y, et al. A phase II randomized trial of pembrolizumab versus cetuximab, concomitant with radiotherapy (RT) in locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN): first results of the GORTEC 2015–01 “PembroRad” trial. J Clin Oncol. 2018; 36(15): 6018.
- 38Weiss J, Bauman JR, Deal AM, et al. Preliminary toxicity data from the combination of pembrolizumab and definitive-dose radiotherapy for locally advanced head and neck cancer with contraindication to cisplatin therapy. J Clin Oncol. 2018; 36(15): 6069.
- 39Tao Y, Auperin A, Sun XS, et al. Avelumab–cetuximab–radiotherapy (RT) versus standards of care in locally advanced squamous cell carcinoma of the head and neck (SCCHN): the safety phase of a randomized phase III trial GORTEC 2017-01 (REACH). Eur J Cancer. 2020; 141: 21-29.
Citing Literature
