How to Cite
Abstract
Introduction. Evaluating the efficacy of using trastuzumab either de novo or as a continuation of therapy compared to chemotherapy alone in the second line for patients with HER2-positive tumors is a clinically relevant task.
Aim. To compare progression-free survival (PFS) and overall survival (OS) in patients with metastatic gastric cancer who received second-line trastuzumab either de novo or as continuation therapy after progression on a first-line trastuzumab-containing regimen, versus patients who received cytostatic chemotherapy alone in the second line.
Materials and Methods. After excluding patients who received ramucirumab or immune checkpoint inhibitors (ICIs) in the second line, 87 patients with morphologically confirmed metastatic gastric/gastroesophageal junction (GEJ) or and HER2 3+ or 2+ with amplification, who progressed on first-line treatment, were identified from the registry. All patients were divided into three groups: chemotherapy alone (n=18), trastuzumab de novo (n=38), and trastuzumab continuation (n=31). The median follow-up time was 34.1 months (range 3.5–95.8).
Results. Median PFS was 4.1 months in the chemotherapy group, 6.0 months in the de novo trastuzumab group (p=0.037; HR 0.47; 95% CI 0.24–0.97), and 5.8 months in the continuation trastuzumab group (p=0.29; HR 0.97; 95% CI 0.91–1.03). Median OS was 11.0 months in the chemotherapy group, 14.2 months in the de novo trastuzumab group (p=0.392; HR 0.73; 95% CI 0.36–1.45), and 11.7 months in the continuation group (p=0.94; HR 0.97; 95% CI 0.46–2.04) compared to the chemotherapy group. Efficacy of trastuzumab in the continuation group also did not differ between patients with (n=5) and without (n=26) metastatic rebiopsy (median PFS: 6.7 vs. 5.5 months, p=0.067; median OS: 13.0 vs. 10.8 months, p=0.91).
Conclusion. The use of trastuzumab after disease progression on the first line does not improve long-term outcomes, regardless of whether it is initiated de novo or continued from the first line. To achieve optimal survival outcomes in patients with metastatic gastric/GEJ cancer, HER2 status should be determined prior to or during first-line treatment.
References
Gravalos C., Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008; 19: 1523-29.-DOI: https://doi.org/10.1093/annonc/mdn169.
Roviello G., Catalano M., Iannone L.F., et al. Current status and future perspectives in HER2 positive advanced gastric cancer. Clin Transl Oncol. 2022; 24(6): 981-996.-DOI: https://doi.org/10.1007/s12094-021-02760-0.
Malla R.R., Nellipudi H.R., Srilatha M., et al. HER-2 positive gastric cancer: Current targeted treatments. Int J Biol Macromol. 2024; 274(Pt 1): 133247.-DOI: https://doi.org/10.1016/j.ijbiomac.2024.133247.
Bang Y.-J., Van Cutsem E., Feyereislova A., et al. 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. 2010; 376(9742): 687-97.-DOI: https://doi.org/10.1016/S0140-6736(10)61121-X.
Tabernero J., Hoff P.M., Shen L., et al. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018; 19(10): 1372-1384.-DOI: https://doi.org/10.1016/S1470-2045(18)30481-9.
Семёнов Н.Н., Федянин М.Ю., Жукова Л.Г., et al. Оценка эффективности второй линии терапии при метастатическом раке желудка в реальной клинической практике — результаты многоцентрового ретроспективного исследования. Опыт онкологической службы Москвы. Вопросы онкологии. 2024; 70(6): 1189-1198.-DOI: https://doi.org/10.37469/0507- 3758-2024-70-6-1189-1198. [Nikolay N. Semenov, Mikhail Yu. Fedyanin, Ludmila G. Zhukova, et al. Evaluation of the efficacy of second-line therapy for metastatic gastric cancer in real clinical practice - the results of a multicenter retrospective study: experience of Moscow oncology service. Voprosy Onkologii = Problems in Oncology. 2024; 70(6): 1189-1198.-DOI: https://doi.org/10.37469/0507-3758-2024-70-6-1189-1198 (In Rus)].
Makiyama A., Sukawa Y., Kashiwada T., et al. Randomized, phase II study of trastuzumab beyond progression in patients with HER2-positive advanced gastric or gastroesophageal junction cancer: WJOG7112G (T-ACT Study). J Clin Oncol. 2020; 38(17): 1919-1927.-DOI: https://doi.org/10.1200/JCO.19.03077.
Takahashi M., Sakamoto Y., Otsuka K., et al. Phase II study of the reuse of trastuzumab with docetaxel beyond progression after first-line treatment in second-line treatment for unresectable, metastatic gastric cancer (T-CORE1203). Tohoku J Exp Med. 2021; 254(1): 49-55.-DOI: https://doi.org/10.1620/tjem.254.49.
Kawamoto Y., Yuki S., Meguro T., et al. Phase II study of continued trastuzumab plus irinotecan in patients with HER2-positive gastric cancer previously treated with trastuzumab (HGCSG 1201). Oncologist. 2022; 27(5): 340-e374.-DOI: https://doi.org/10.1093/oncolo/oyab062.
Thuss-Patience P.C., Shah M.A., Ohtsu A., et al. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017; 18(5): 640-653.-DOI: https://doi.org/10.1016/S1470-2045(17)30111-0.
Satoh T., Xu R.-H., Chung H.C., et al. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study. J Clin Oncol. 2014; 32(19): 2039-49.-DOI: https://doi.org/10.1200/JCO.2013.53.6136.
Shitara K., Bang Y.-J., Iwasa S., et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020; 382(25): 2419-2430.-DOI: https://doi.org/10.1056/NEJMoa2004413.
Van Cutsem E., di Bartolomeo M., Smyth E., et al. Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02): primary and updated analyses from a single-arm, phase 2 study. Lancet Oncol. 2023; 24(7): 744-756.-DOI: https://doi.org/10.1016/S1470-2045(23)00215-2.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
© АННМО «Вопросы онкологии», Copyright (c) 2026