Top

International Journal of Clinical Oncology

Published in:

21-11-2022 | Gastric Cancer | Original Article

Treatment efficacy of ramucirumab-containing chemotherapy in patients with alpha-fetoprotein producing gastric cancer

Authors: Daisaku Kamiimabeppu, Takeru Wakatsuki, Daisuke Takahari, Naoki Fukuda, Keitaro Shimozaki, Hiroki Osumi, Izuma Nakayama, Mariko Ogura, Akira Ooki, Eiji Shinozaki, Keisho Chin, Kensei Yamaguchi

Published in: International Journal of Clinical Oncology | Issue 1/2023

Abstract

Background

Alpha-Fetoprotein Producing Gastric Cancer (AFPGC) is an aggressive subgroup of gastric cancer. Recently ramucirumab has shown survival benefits in hepatocellular carcinoma, but only in those with higher Alpha-Fetoprotein (AFP) levels. However, the efficacy of ramucirumab-containing chemotherapy in AFPGC remains unclear.

Methods

We retrospectively assessed 352 patients who received ramucirumab-containing chemotherapy between June 2015 and December 2019. AFPGC was defined when serum AFP levels were elevated at diagnosis and correlated with the disease state during treatment. Non-AFPGC was defined when serum AFP levels were normal at diagnosis.

Results

Among the 352 patients, 28 patients were defined as AFPGC and 246 patients were defined as non-AFPGC. AFPGC was characterized by high frequency of liver metastasis and low frequency of peritoneal metastasis compared to non-AFPGC. Ramucirumab containing chemotherapy showed higher response rates in AFPGC (39.1% vs 24.8%, p = 0.198) and disease control rates (86.9% vs 61.5%, p = 0.028) than those of non-AFPGC, respectively. Median progression-free survival (PFS) was 5.5 months (95%CI 3.9–7.1) in AFPGC and 4.0 months (95%CI 3.6–4.6) in non-AFPGC (HR: 0.91, 95% CI 0.61–1.36, p = 0.66), and median overall survival (OS) was 10.7 months (95% CI 7.4–20.8) in AFPGC and 9.2 months (95% CI 8.1–10.4) in non-AFPGC (HR: 0.72, 95% CI 0.48–1.08, p = 0.11), respectively. In multivariate analysis, AFPGC was not a negative prognostic factor both for PFS and OS.

Conclusion

Ramucirumab containing chemotherapy showed higher response and comparable survival in AFPGC compared to those of non-AFPGC. Considering the generally poor prognosis of AFPGC, ramucirumab-containing chemotherapy might be a promising treatment option in AFPGC.

Available only for authorised users

Bergstrand CG, Czar B (1956) Demonstration of a new protein fraction in serum from the human fetus. Scand J Clin Lab Invest 8:174–179CrossRef

Smith CJ, Ajdukiewicz A, Kelleher PC (1983) Concanavalin-a-affinity molecular heterogeneity of human hepatoma AFP and cord-serum AFP. Ann N Y Acad Sci 417:69–74CrossRef

Norgaard-Pedersen B, Albrechtsen R, Teilum G (1975) Serum alphafoetoprotein as a marker for endodermal sinus tumour (yolk sac tumour) or a vitelline component of “teratocarcinoma.” Acta Pathologica et Microbiologica Scand Sec A Pathol 83(6):573–589

European Association for the Study of the Liver (2019) EASL clinical practice guidelines management of hepatocellular carcinoma. J Hepatol 69(1):182–236

Metzgeroth G, Strobel P, Baumbusch T et al (2010) Hepatoid adenocarcinoma review of the literature illustrated by a rare case originating in the peritoneal cavity. Onkologie 33:263–269CrossRef

Kinjo T, Taniguchi H, Kushima R et al (2012) Histologic and immunohistochemical analyses of α-fetoprotein-producing cancer of the stomach. Am J Surg Pathol 36:56–65CrossRef

Yamagata T, Yamagata Y, Nakanishi M et al (2004) A case of primary lung cancer producing alpha-fetoprotein. Can Respir J 11:504–506CrossRef

Matsueda K, Yamamoto H, Yoshida Y et al (2006) Hepatoid carcinoma of the pancreas producing protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP). J Gastroenterol 41:1011–1019CrossRef

Devi NR, Sathyalakshmi R, Devi J et al (2015) Hepatoid adenocarcinoma of the gall bladder-a rare variant. J Clin Diagn Res JCDR. https://doi.org/10.7860/JCDR/2015/10799.6324CrossRef

10.

Cappetta A, Bergamo F, Mescoli C et al (2012) Hepatoid adenocarcinoma of the colon: what should we target? Pathol Oncol Res 18:93–96CrossRef

11.

Bourreille J, Metayer P, Sauger F et al (1970) Existence of alpha feto protein during gastric-origin secondary cancer of the liver. Presse Med 78:1277–1278

12.

McIntire KR, Waldmann TA, Moertel CG et al (1975) Serum alphafetoprotein in patients with neoplasms of the gastrointestinal tract. Cancer Res 35(4):991–996

13.

Chang YC, Nagasue N, Kohno H et al (1990) Clinicopathologic features and long-term results of alphafetoprotein-producing gastric cancer. Am J Gastroenterol 85(11):1480–1485

14.

Adachi Y, Tsuchihashi J, Shiraishi N et al (2003) AFP-producing gastric carcinoma: multivariate analysis of prognostic factors in 270 patients. Oncology 65(2):95–101CrossRef

15.

Bozkaya Y, Demirci NS, Kurtipek A et al (2017) Clinicopathological and prognostic characteristics in patients with AFP-secreting gastric carcinoma. Mol Clin Oncol 7(2):267–274CrossRef

16.

Fuchs CS, Tomasek J, Yong CJ et al (2014) Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): An international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 383:31–39CrossRef

17.

Wilke H, Muro K, Van Cutsem E et al (2014) Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): A double-blind, randomised phase 3 trial. Lancet Oncol 15:1224–1235CrossRef

18.

Zhu AX, Park JO, Ryoo BY et al (2015) Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol 16(7):859–870CrossRef

19.

Zhu AX, Kang YK, Yen CJ et al (2019) Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 20(2):282–296CrossRef

20.

Inagawa S, Shimazaki J, Hori M et al (2001) Hepatoid adenocarcinoma of the stomach. Gastric Cancer 4(1):43–52CrossRef

21.

Inoue M, Sano T, Kuchiba A et al (2010) Long-term results of gastrectomy for alpha-fetoprotein-producing gastric cancer. Br J Surg 97(7):1056–1061CrossRef

22.

Yoshizawa J, Ishizone S, Ikeyama M et al (2017) Gastric hepatoid adenocarcinoma resulting in a spontaneous gastric perforation: a case report and review of the literature. BMC Cancer 17(1):368CrossRef

23.

He R, Yang Q, Dong X et al (2017) Clinicopathologic and prognostic characteristics of alpha-fetoprotein-producing gastric cancer. Oncotarget 8(14):23817–23830CrossRef

24.

Wang Y-K, Shen L, Jiao Xi et al (2018) Predictive and prognostic value of serum AFP level and its dynamic changes in advanced gastric cancer patients with elevated serum AFP. World J Gastroenterol 24(2):266–273CrossRef

25.

Li N, Bai C, Zhang R et al (2021) Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer. Translat Oncolo 14(2):101004CrossRef

26.

Kanda Y (2013) Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant 48:452–458CrossRef

27.

Bang YJ, Van Cutsem E, Feyereislova A et al (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 376:687–697CrossRef

28.

Kang YK, Boku N, Satoh T et al (2017) Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390(10111):2461–2471CrossRef

29.

Yoshioka M, Inoue N, Someda H et al (2011) A case of AFP-producing gastric cancer resected after efficient S-1/CDDP combination chemotherapy. Gan To Kagaku Ryoho 38(1):105

30.

Fukuda K, Ito S, Shimizu K et al (2013) Retrospective analysis concerning AFP-producing gastric cancer. Gan Kagaku Ryoho 40(2):191

31.

Kunoki N, Nishiyama R, Ryuzaki H et al (2008) A case of alpha-fetoprotein-producing gastric cancer with hepatic metastasis successfully treated with combination chemotherapy. Nihon Shokakibyo Gakkai Zasshi 105(10):1489

32.

Arakawa Y, Tamura M, Aiba K et al (2017) Significant response to ramucirumab monotherapy in chemotherapy-resistant recurrent alpha-fetoprotein-producing gastric cancer: a case report. Oncol Lett 14(3):3039–3042CrossRef

33.

Takada J, Araki H, Ozawa N et al (2019) Effective treatment of cytotoxic agent refractory alpha-fetoprotein-producing gastric cancer with ramucirumab: a case report and review of the literature. J Gastrointest Canc 50:556–559CrossRef

34.

Iida A, Katayama K, Yamaguchi A (2013) Five-year survival of alpha-fetoprotein-producing gastric cancer with synchronous liver metastasis: a case report. J Gastric Cancer 13:58–64CrossRef

35.

Fang YU, Wang L, Yang N et al (2015) Successful multimodal therapy for an α-fetoprotein-producing gastric cancer patient with simultaneous liver metastases. Oncol Lett 10:3021–3025CrossRef

36.

Di Bartolomeo M, Niger M, Tirino G et al (2018) Ramucirumab as second-line therapy in metastatic gastric cancer: real-world data from the ramoss study. Target Oncol 13(2):227–234CrossRef

37.

Lu J, Ding Y, Chen Y et al (2021) Whole-exome sequencing of alpha-fetoprotein producing gastric carcinoma reveals genomic profile and therapeutic targets. Nat Commun 12(1):3946CrossRef

38.

Liu D, Li B, Yan B et al (2020) The clinicopathological features and prognosis of serum AFP positive gastric cancer: a report of 16 cases. Int J Clin Exp Pathol 13(9):2439–2446

39.

Yamashita T, Forgues M, Wang W et al (2008) EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res 68:1451–1461CrossRef

40.

Shan YF, Huang YL, Xie YK et al (2011) Angiogenesis and clinicopathologic characteristics in different hepatocellular carcinoma subtypes defined by EpCAM and alpha-fetoprotein expression status. Med Oncol 28:1012–1016CrossRef

41.

Zucman-Rossi J, Villanueva A, Nault JC et al (2015) Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology 149:1226–1239CrossRef

42.

Koide N, Nishio A, Igarashi J et al (1999) Alpha-fetoprotein-producing gastric cancer: Histochemical analysis of cell proliferation, apoptosis, and angiogenesis. Am J Gastroenterol 94:1658–1663CrossRef

43.

Kamei S, Kono K, Amemiya H et al (2003) Evaluation of VEGF and VEGF-C expression in gastric cancer cells producing alpha-fetoprotein. J Gastroenterol 38:540–547CrossRef

44.

Wang Y, Sun L, Li Z et al (2019) Hepatoid adenocarcinoma of the stomach: a unique subgroup with distinct clinicopathological and molecular features. Gastric Cancer 22:1183–1192CrossRef

Title: Treatment efficacy of ramucirumab-containing chemotherapy in patients with alpha-fetoprotein producing gastric cancer
Authors: Daisaku Kamiimabeppu
Takeru Wakatsuki
Daisuke Takahari
Naoki Fukuda
Keitaro Shimozaki
Hiroki Osumi
Izuma Nakayama
Mariko Ogura
Akira Ooki
Eiji Shinozaki
Keisho Chin
Kensei Yamaguchi
Publication date: 21-11-2022
Publisher: Springer Nature Singapore
Keywords: Gastric Cancer
Hepatocellular Carcinoma
Gastric Cancer
Hepatocellular Carcinoma
Ramucirumab
Cytostatic Therapy
Published in: International Journal of Clinical Oncology / Issue 1/2023
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-022-02263-0

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2023

Risk of mortality and other adverse outcomes from myocardial infarction in cancer survivors: a meta-analysis

Current clinical perspective of urological oncology in the adolescent and young adult generation

Overall survival analysis of patients enrolled in a randomized phase III trial comparing gefitinib and erlotinib for previously treated advanced lung adenocarcinoma (WJOG5108LFS)

Comparative analysis of surgical and oncologic outcomes of robotic, laparoscopic and open radical nephrectomy with venous thrombectomy: a propensity-matched cohort study

Survival after laparoscopic radical surgery for stage IA–IIB cervical cancer: 1316 consecutive cases from a national laparoscopic training center in China

Relative dose intensity and 1-year psoas muscle index reduction rate as prognostic factors in gastric cancer patients with postoperative adjuvant chemotherapy

Keynote webinar | Spotlight on antibody–drug conjugates in cancer