Safety and efficacy of trastuzumab administered as a 30-min infusion in patients with HER2-positive advanced gastric cancer
- 59 Downloads
To investigate the safety and efficacy of 30-min maintenance infusions of trastuzumab in advanced gastric cancer positive for human epidermal growth factor receptor 2 (HER2).
This was a retrospective study conducted across five Korean hospitals in patients with HER2-positive gastric or gastroesophageal junction adenocarcinoma treated with first-line, 3-weekly trastuzumab plus chemotherapy. The first dose of trastuzumab (8 mg/kg) was administered as a 90-min infusion, with all subsequent maintenance infusions (6 mg/kg) given over 30 min. The primary aim was to investigate infusion-related reactions and cardiac events with 30-min infusions of trastuzumab. Objective response rate, progression-free survival, and overall survival were secondary endpoints.
The study included 128 patients (efficacy population), of whom 123 received both induction and maintenance infusions and formed the safety population. The median age was 63 years; 80% were presenting for the first time with metastatic disease, and 94% were treated with trastuzumab plus capecitabine/cisplatin. Infusion-related reactions were observed in 32 of 123 patients (26%). There were no cardiac events. The most frequent adverse events were anorexia and nausea, followed by vomiting, fatigue, mucositis, sensory neuropathy, and hand–foot syndrome. Most events were grade 1–2 and were manageable. No patient discontinued study treatment due to adverse events. The objective response rate was 63%, and included 6 complete responses.
Trastuzumab 30-min maintenance infusions were well tolerated with a good safety profile, and resulted in sustained efficacy in patients with HER2-positive advanced gastric cancer.
Keywords30-min infusion Trastuzumab Gastric cancer Chemotherapy Rapid infusion HER2
Medical writing support (including development of a draft outline and subsequent drafts in consultation with the authors, assembling tables and figures, collating author comments, copyediting, fact checking and referencing) was provided by Rick Flemming PhD, CMPP at Aspire Scientific Limited (Bollington, UK) and was funded by CELLTRION Healthcare Co., Ltd. (Incheon, Republic of Korea). We thank all patients involved in this study.
SYO and JGK were involved in study conception and design, acquisition of data, and analysis/interpretation of data. SJH, BWK, HJL, and JHK were involved in acquisition of data, and analysis/interpretation of data. JL, SL, STK, SHP, JHK, HYL, and WKK were involved in acquisition of data. HK was involved in analysis and interpretation of data. All authors had full access to all the data in the study, reviewed drafts of the manuscript, approved the final version, had final responsibility for the decision to submit for publication, and agree to be accountable for the work.
This work was supported by the Dong-A University Research Fund.
Compliance with ethical standards
Conflict of interest
HoUng Kim is an employee of CELLTRION Healthcare Co., Ltd. All other authors declare that they have no conflict of interest.
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. For this type of study formal consent is not required.
- 1.World Health Organization. International Agency for Research on Cancer (2012) GLOBOCAN 2012. Estimated cancer incidence, mortality and prevalence worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed 14 Mar 2018
- 2.Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376(9742):687–697. https://doi.org/10.1016/s0140-6736(10)61121-x CrossRefGoogle Scholar
- 3.Cabebe EC (2018) Gastric cancer. Practice essentials. Medscape, LLC. https://emedicine.medscape.com/article/278744-overview. Accessed 15 Mar 2018
- 12.Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman G, Slamon DJ (1999) Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 17(9):2639–2648. https://doi.org/10.1200/jco.19126.96.36.19939 CrossRefGoogle Scholar
- 13.Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Lang I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Ruschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353(16):1659–1672. https://doi.org/10.1056/NEJMoa052306 CrossRefGoogle Scholar
- 14.Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353(16):1673–1684. https://doi.org/10.1056/NEJMoa052122 CrossRefGoogle Scholar
- 15.Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ, Press M (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20(3):719–726. https://doi.org/10.1200/jco.2002.20.3.719 CrossRefGoogle Scholar
- 16.Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792. https://doi.org/10.1056/nejm200103153441101 CrossRefGoogle Scholar
- 17.Genentech Inc (2017) Highlights of prescribing information. Herceptin® (trastuzumab) for injection, for intravenous use. https://www.gene.com/download/pdf/herceptin_prescribing.pdf. Accessed 12 June 2018
- 19.Abe H, Mori T, Kawai Y, Tomida K, Yamazaki K, Kubota Y, Umeda T, Tani T (2013) Safety assessment of intravenous administration of trastuzumab in 100 ml saline for the treatment of HER2-positive breast cancer patients. Asian Pac J Cancer Prev 14(8):4843–4846Google Scholar
- 20.Baselga J, Carbonell X, Castaneda-Soto NJ, Clemens M, Green M, Harvey V, Morales S, Barton C, Ghahramani P (2005) Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule. J Clin Oncol 23(10):2162–2171. https://doi.org/10.1200/jco.2005.01.014 CrossRefGoogle Scholar
- 22.Abe H, Umeda T, Kawai Y, Tanaka M, Mori T, Cho H, Kubota Y, Mekata E, Kurumi Y, Tani T (2010) Adjuvant trastuzumab can be infused safely over 30 minutes. Gan To Kagaku Ryoho 37(10):1887–1891Google Scholar
- 24.Papouchado BG, Myles J, Lloyd RV, Stoler M, Oliveira AM, Downs-Kelly E, Morey A, Bilous M, Nagle R, Prescott N, Wang L, Dragovich L, McElhinny A, Garcia CF, Ranger-Moore J, Free H, Powell W, Loftus M, Pettay J, Gaire F, Roberts C, Dietel M, Roche P, Grogan T, Tubbs R (2010) Silver in situ hybridization (SISH) for determination of HER2 gene status in breast carcinoma: comparison with FISH and assessment of interobserver reproducibility. Am J Surg Pathol 34(6):767–776. https://doi.org/10.1097/PAS.0b013e3181d96231 CrossRefGoogle Scholar
- 25.Dietel M, Ellis IO, Hofler H, Kreipe H, Moch H, Dankof A, Kolble K, Kristiansen G (2007) Comparison of automated silver enhanced in situ hybridisation (SISH) and fluorescence ISH (FISH) for the validation of HER2 gene status in breast carcinoma according to the guidelines of the American Society of Clinical Oncology and the College of American Pathologists. Virchows Arch 451(1):19–25. https://doi.org/10.1007/s00428-007-0424-5 CrossRefGoogle Scholar
- 26.Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. https://doi.org/10.1016/j.ejca.2008.10.026 CrossRefGoogle Scholar
- 28.Pritchard CH, Greenwald MW, Kremer JM, Gaylis NB, Rigby W, Zlotnick S, Chung C, Jaber B, Reiss W (2014) Safety of infusing rituximab at a more rapid rate in patients with rheumatoid arthritis: results from the RATE-RA study. BMC Musculoskelet Disord 15:177. https://doi.org/10.1186/1471-2474-15-177 CrossRefPubMedPubMedCentralGoogle Scholar