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Published in: Gastric Cancer 4/2020

Open Access 01-07-2020 | Systemic Therapy | Original Article

Increased assessment of HER2 in metastatic gastroesophageal cancer patients: a nationwide population-based cohort study

Authors: Willemieke P. M. Dijksterhuis, Rob H. A. Verhoeven, Sybren L. Meijer, Marije Slingerland, Nadia Haj Mohammad, Judith de Vos-Geelen, Laurens V. Beerepoot, Theo van Voorthuizen, Geert-Jan Creemers, Martijn G. H. van Oijen, Hanneke W. M. van Laarhoven

Published in: Gastric Cancer | Issue 4/2020

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Abstract

Background

Addition of trastuzumab to first-line palliative chemotherapy in gastroesophageal cancer patients with HER2 overexpression has shown to improve survival. Real-world data on HER2 assessment and administration of trastuzumab are lacking. The aim of this study was to assess HER2 testing, trastuzumab administration, and overall survival (OS) in a nationwide cohort of metastatic gastroesophageal cancer patients.

Methods

Data of patients with synchronous metastatic gastroesophageal adenocarcinoma diagnosed in 2010–2016 that received palliative systemic treatment (n = 2846) were collected from the Netherlands Cancer Registry and Dutch Pathology Registry. The ToGA trial criteria were used to determine HER2 overexpression. Proportions of HER2 tested patients were analyzed between hospital volume categories using Chi-square tests, and over time using trend analysis. OS was tested using the Kaplan Meier method with log rank test.

Results

HER2 assessment increased annually, from 18% in 2010 to 88% in 2016 (P < 0.01). Median OS increased from 6.9 (2010–2013) to 7.9 months (2014–2016; P < 0.05). Between the hospitals, the proportion of tested patients varied between 29–100%, and was higher in high-volume hospitals (P < 0.01). Overall, 77% of the HER2 positive patients received trastuzumab. Median OS was higher in patients with positive (8.8 months) and negative (7.4 months) HER2 status, compared to non-tested patients (5.6 months; P < 0.05).

Conclusion

Increased determination of HER2 and administration of trastuzumab have changed daily practice management of metastatic gastroesophageal cancer patients receiving palliative systemic therapy, and possibly contributed to their improved survival. Further increase in awareness of HER2 testing and trastuzumab administration may improve quality of care and patient outcomes.
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Literature
1.
go back to reference Ter VE, Mohammad NH, Van Valkenhoef G, Ngai LL, Mali RMA, Anderegg MC, et al. The efficacy and safety of first-line chemotherapy in advanced esophagogastric cancer: a network meta-analysis. J Natl Cancer Inst. 2016;108:1–13. Ter VE, Mohammad NH, Van Valkenhoef G, Ngai LL, Mali RMA, Anderegg MC, et al. The efficacy and safety of first-line chemotherapy in advanced esophagogastric cancer: a network meta-analysis. J Natl Cancer Inst. 2016;108:1–13.
2.
go back to reference Al-Batran SE, Ajani JA. Impact of chemotherapy on quality of life in patients with metastatic esophagogastric cancer. Cancer. 2010;116:2511–8.PubMed Al-Batran SE, Ajani JA. Impact of chemotherapy on quality of life in patients with metastatic esophagogastric cancer. Cancer. 2010;116:2511–8.PubMed
3.
go back to reference Janmaat VT, Steyerberg EW, van der Gaast A, Mathijssen RHJ, Bruno MJ, Peppelenbosch MP, et al. Palliative chemotherapy and targeted therapies for esophageal and gastroesophageal junction cancer. Cochrane Database Syst Rev. 2017;11:CD004063 Janmaat VT, Steyerberg EW, van der Gaast A, Mathijssen RHJ, Bruno MJ, Peppelenbosch MP, et al. Palliative chemotherapy and targeted therapies for esophageal and gastroesophageal junction cancer. Cochrane Database Syst Rev. 2017;11:CD004063
5.
go back to reference Haj Mohammad N, ter Veer E, Ngai L, Mali R, van Oijen MGH, van Laarhoven HWM. Optimal first-line chemotherapeutic treatment in patients with locally advanced or metastatic esophagogastric carcinoma: triplet versus doublet chemotherapy: a systematic literature review and meta-analysis. Cancer Metastasis Rev. 2015;34:429–41.CrossRef Haj Mohammad N, ter Veer E, Ngai L, Mali R, van Oijen MGH, van Laarhoven HWM. Optimal first-line chemotherapeutic treatment in patients with locally advanced or metastatic esophagogastric carcinoma: triplet versus doublet chemotherapy: a systematic literature review and meta-analysis. Cancer Metastasis Rev. 2015;34:429–41.CrossRef
6.
go back to reference Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki 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;376:687–97. https://doi.org/10.1016/S0140-6736(10)61121-X.CrossRefPubMed Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki 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;376:687–97. https://​doi.​org/​10.​1016/​S0140-6736(10)61121-X.CrossRefPubMed
7.
go back to reference Satoh T, Bang Y-J, Gotovkin EA, Hamamoto Y, Kang Y-K, Moiseyenko VM, et al. Quality of life in the trastuzumab for gastric cancer trial. Oncologist. 2014;19:712–9.CrossRef Satoh T, Bang Y-J, Gotovkin EA, Hamamoto Y, Kang Y-K, Moiseyenko VM, et al. Quality of life in the trastuzumab for gastric cancer trial. Oncologist. 2014;19:712–9.CrossRef
8.
go back to reference Lordick F, Mariette C, Haustermans K, Obermannová R, Arnold D. Oesophageal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27:50–7.CrossRef Lordick F, Mariette C, Haustermans K, Obermannová R, Arnold D. Oesophageal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27:50–7.CrossRef
9.
go back to reference Ajani JA, D’Amico TA, Almhanna K, Bentrem DJ, Chao J, Das P, et al. Gastric cancer, version 3.2016; clinical practice guidelines in oncology. JNCCN J Natl Compr Cancer Netw. 2016;14:1286–312.CrossRef Ajani JA, D’Amico TA, Almhanna K, Bentrem DJ, Chao J, Das P, et al. Gastric cancer, version 3.2016; clinical practice guidelines in oncology. JNCCN J Natl Compr Cancer Netw. 2016;14:1286–312.CrossRef
10.
go back to reference Ajani JA, D’Amico TA, Almhanna K, Bentrem DJ, Chao J, Das P, et al. Esophageal and esophagogastric junction cancers, Version 1.2015. JNCCN J Natl Compr Cancer Netw. 2016;13:194–227.CrossRef Ajani JA, D’Amico TA, Almhanna K, Bentrem DJ, Chao J, Das P, et al. Esophageal and esophagogastric junction cancers, Version 1.2015. JNCCN J Natl Compr Cancer Netw. 2016;13:194–227.CrossRef
11.
go back to reference Kodera Y, Sano T. Japanese gastric cancer treatment guidelines 2014 (ver 4). Gastric Cancer. 2017;20:1–19.CrossRef Kodera Y, Sano T. Japanese gastric cancer treatment guidelines 2014 (ver 4). Gastric Cancer. 2017;20:1–19.CrossRef
12.
go back to reference Bartley AN, Washington MK, Ventura CB, Ismaila N, Colasacco C, Al Benson B, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma guideline from the College of American Pathologists, American Society for clinical Pathology, and American Society of Clinical Oncology. Am J Clin Pathol. 2016;146:647–69.CrossRef Bartley AN, Washington MK, Ventura CB, Ismaila N, Colasacco C, Al Benson B, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma guideline from the College of American Pathologists, American Society for clinical Pathology, and American Society of Clinical Oncology. Am J Clin Pathol. 2016;146:647–69.CrossRef
14.
go back to reference Van Cutsem E, Bang YJ, Feng-yi F, Xu JM, Lee KW, Jiao SC, et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer Jpn. 2015;18:476–84.CrossRef Van Cutsem E, Bang YJ, Feng-yi F, Xu JM, Lee KW, Jiao SC, et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer Jpn. 2015;18:476–84.CrossRef
15.
go back to reference Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008;19:1523–9.CrossRef Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008;19:1523–9.CrossRef
16.
go back to reference Park D, Yun JW, Park JH, Oh SJ, Kim HJ, Cho YK, et al. HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci. 2006;51:1371–9.CrossRef Park D, Yun JW, Park JH, Oh SJ, Kim HJ, Cho YK, et al. HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci. 2006;51:1371–9.CrossRef
17.
go back to reference Busweiler LAD, Dikken JL, Henneman D, van Berge Henegouwen MI, Ho VKY, Tollenaar RAEM, et al. The influence of a composite hospital volume on outcomes for gastric cancer surgery: a Dutch population-based study. J Surg Oncol. 2017;115:738–45.CrossRef Busweiler LAD, Dikken JL, Henneman D, van Berge Henegouwen MI, Ho VKY, Tollenaar RAEM, et al. The influence of a composite hospital volume on outcomes for gastric cancer surgery: a Dutch population-based study. J Surg Oncol. 2017;115:738–45.CrossRef
18.
go back to reference Dikken JL, Van Sandick JW, Allum WH, Johansson J, Jensen LS, Putter H, et al. Differences in outcomes of oesophageal and gastric cancer surgery across Europe. Br J Surg. 2013;100:83–94.CrossRef Dikken JL, Van Sandick JW, Allum WH, Johansson J, Jensen LS, Putter H, et al. Differences in outcomes of oesophageal and gastric cancer surgery across Europe. Br J Surg. 2013;100:83–94.CrossRef
19.
go back to reference Wouters MWJM, Gooiker GA, Van Sandick JW, Tollenaar RAEM. The volume-outcome relation in the surgical treatment of esophageal cancer: a systematic review and meta-analysis. Cancer. 2012;118:1754–63.CrossRef Wouters MWJM, Gooiker GA, Van Sandick JW, Tollenaar RAEM. The volume-outcome relation in the surgical treatment of esophageal cancer: a systematic review and meta-analysis. Cancer. 2012;118:1754–63.CrossRef
20.
go back to reference Van Putten M, Verhoeven RHA, Van Sandick JW, Plukker JTM, Lemmens VEPP, Wijnhoven BPL, et al. Hospital of diagnosis and probability of having surgical treatment for resectable gastric cancer. Br J Surg. 2016;103:233–41.CrossRef Van Putten M, Verhoeven RHA, Van Sandick JW, Plukker JTM, Lemmens VEPP, Wijnhoven BPL, et al. Hospital of diagnosis and probability of having surgical treatment for resectable gastric cancer. Br J Surg. 2016;103:233–41.CrossRef
21.
go back to reference van Putten M, Nelen SD, Lemmens VEPP, Stoot JHMB, Hartgrink HH, Gisbertz SS, et al. Overall survival before and after centralization of gastric cancer surgery in the Netherlands. Br J Surg. 2018;105:1807–15.CrossRef van Putten M, Nelen SD, Lemmens VEPP, Stoot JHMB, Hartgrink HH, Gisbertz SS, et al. Overall survival before and after centralization of gastric cancer surgery in the Netherlands. Br J Surg. 2018;105:1807–15.CrossRef
23.
go back to reference Varagunam M, Hardwick R, Riley S, Chadwick G, Cromwell DA, Groene O. Changes in volume, clinical practice and outcome after reorganisation of oesophago-gastric cancer care in England: a longitudinal observational study. Eur J Surg Oncol Engl. 2018;44:524–31.CrossRef Varagunam M, Hardwick R, Riley S, Chadwick G, Cromwell DA, Groene O. Changes in volume, clinical practice and outcome after reorganisation of oesophago-gastric cancer care in England: a longitudinal observational study. Eur J Surg Oncol Engl. 2018;44:524–31.CrossRef
24.
go back to reference Bachmann MO, Alderson D, Edwards D, Wotton S, Bedford C, Peters TJ, et al. Cohort study in South and West England of the influence of specialization on the management and outcome of patients with oesophageal and gastric cancers. Br J Surg. Engl. 2002;89:914–22.CrossRef Bachmann MO, Alderson D, Edwards D, Wotton S, Bedford C, Peters TJ, et al. Cohort study in South and West England of the influence of specialization on the management and outcome of patients with oesophageal and gastric cancers. Br J Surg. Engl. 2002;89:914–22.CrossRef
25.
go back to reference Markar SR, Karthikesalingam A, Thrumurthy S, Low DE. Volume-outcome relationship in surgery for esophageal malignancy: systematic review and meta-analysis. J Gastrointest Surg. 2012;5:1055–63.CrossRef Markar SR, Karthikesalingam A, Thrumurthy S, Low DE. Volume-outcome relationship in surgery for esophageal malignancy: systematic review and meta-analysis. J Gastrointest Surg. 2012;5:1055–63.CrossRef
26.
go back to reference Birkmeyer JD, Dimick JB. Understanding and reducing variation in surgical mortality. Annu Rev Med. 2008;60:405–15.CrossRef Birkmeyer JD, Dimick JB. Understanding and reducing variation in surgical mortality. Annu Rev Med. 2008;60:405–15.CrossRef
27.
go back to reference Rüschoff J, Hanna W, Bilous M, Hofmann M, Osamura RY, Penault-Llorca F, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol. 2012;25:637–50.CrossRef Rüschoff J, Hanna W, Bilous M, Hofmann M, Osamura RY, Penault-Llorca F, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol. 2012;25:637–50.CrossRef
28.
go back to reference Hofmann M, Stoss O, Shi D, Büttner R, Van De Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: Results from a validation study. Histopathology. 2008;52:797–805.CrossRef Hofmann M, Stoss O, Shi D, Büttner R, Van De Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: Results from a validation study. Histopathology. 2008;52:797–805.CrossRef
29.
go back to reference Fritz A. International classification of diseases for oncology: ICD-O. 3rd ed. Geneva: World Heal. Organ; 2000. Fritz A. International classification of diseases for oncology: ICD-O. 3rd ed. Geneva: World Heal. Organ; 2000.
30.
go back to reference Casparie M, Tiebosch TMG, Burger G, Blauwgeers H, van de Pol A, van Krieken JHJM, et al. Pathology databanking and biobanking in The Netherlands, a central role for PALGA, the nationwide histopathology and cytopathology data network and archive. Cell Oncol. 2007;29:19–24.PubMedPubMedCentral Casparie M, Tiebosch TMG, Burger G, Blauwgeers H, van de Pol A, van Krieken JHJM, et al. Pathology databanking and biobanking in The Netherlands, a central role for PALGA, the nationwide histopathology and cytopathology data network and archive. Cell Oncol. 2007;29:19–24.PubMedPubMedCentral
32.
go back to reference Hage M, Smits MM, Imholz ALT, Louwen M, Koopman T. Pathologic diagnostics of HER2 positivity in gastroesophageal adenocarcinoma. Am J Clin Pathol. 2015;143:257–64.CrossRef Hage M, Smits MM, Imholz ALT, Louwen M, Koopman T. Pathologic diagnostics of HER2 positivity in gastroesophageal adenocarcinoma. Am J Clin Pathol. 2015;143:257–64.CrossRef
33.
go back to reference Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D. Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Eur J Surg Oncol. 2016;27:v38–49. Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D. Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Eur J Surg Oncol. 2016;27:v38–49.
36.
go back to reference Lammers P, Criscitiello C, Curigliano G, Jacobs I. Barriers to the use of trastuzumab for HER2+ breast cancer and the potential impact of biosimilars: a physician survey in the united states and emerging markets. Pharmaceuticals. 2014;7:943–53.CrossRef Lammers P, Criscitiello C, Curigliano G, Jacobs I. Barriers to the use of trastuzumab for HER2+ breast cancer and the potential impact of biosimilars: a physician survey in the united states and emerging markets. Pharmaceuticals. 2014;7:943–53.CrossRef
38.
go back to reference Fazlollahi L, Remotti HE, Iuga A, Yang HM, Lagana SM, Sepulveda AR. HER2 heterogeneity in gastroesophageal cancer detected by testing biopsy and resection specimens. Arch Pathol Lab Med. 2018;142:516–22.CrossRef Fazlollahi L, Remotti HE, Iuga A, Yang HM, Lagana SM, Sepulveda AR. HER2 heterogeneity in gastroesophageal cancer detected by testing biopsy and resection specimens. Arch Pathol Lab Med. 2018;142:516–22.CrossRef
39.
40.
go back to reference Creemers A, Ter Veer E, De Waal L, Lodder P, Hooijer GKJ, Van Grieken NCT, et al. Discordance in HER2 status in gastro-esophageal adenocarcinomas: a systematic review and meta-analysis. Sci Rep. 2017;7:1–10.CrossRef Creemers A, Ter Veer E, De Waal L, Lodder P, Hooijer GKJ, Van Grieken NCT, et al. Discordance in HER2 status in gastro-esophageal adenocarcinomas: a systematic review and meta-analysis. Sci Rep. 2017;7:1–10.CrossRef
41.
go back to reference Janjigian YY, Werner D, Pauligk C, Steinmetz K, Kelsen DP, Jäger E, et al. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis. Ann Oncol. 2012;23:2656–62.CrossRef Janjigian YY, Werner D, Pauligk C, Steinmetz K, Kelsen DP, Jäger E, et al. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis. Ann Oncol. 2012;23:2656–62.CrossRef
43.
go back to reference Jørgensen JT, Hersom M. HER2 as a prognostic marker in gastric cancer - A systematic analysis of data from the literature. J Cancer. 2012;3:137–44.CrossRef Jørgensen JT, Hersom M. HER2 as a prognostic marker in gastric cancer - A systematic analysis of data from the literature. J Cancer. 2012;3:137–44.CrossRef
44.
go back to reference Creemers A, Ebbing EA, Hooijer GKJ, Stap L, Jibodh-Mulder RA, Gisbertz SS, et al. The dynamics of HER2 status in esophageal adenocarcinoma. Oncotarget. 2018;9:26787–99.CrossRef Creemers A, Ebbing EA, Hooijer GKJ, Stap L, Jibodh-Mulder RA, Gisbertz SS, et al. The dynamics of HER2 status in esophageal adenocarcinoma. Oncotarget. 2018;9:26787–99.CrossRef
45.
go back to reference Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: Phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018;4:1–8.CrossRef Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: Phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018;4:1–8.CrossRef
46.
go back to reference Shitara K, Özgüroğlu M, Bang YJ, Di BM, Mandalà M, Ryu MH, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018;1:123–33.CrossRef Shitara K, Özgüroğlu M, Bang YJ, Di BM, Mandalà M, Ryu MH, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018;1:123–33.CrossRef
47.
49.
go back to reference Pereira MA, Ramos MFKP, Faraj SF, Dias AR, Yagi OK, Zilberstein B, et al. Clinicopathological and prognostic features of Epstein-Barr virus infection, microsatellite instability, and PD-L1 expression in gastric cancer. J Surg Oncol. 2018;117:829–39.CrossRef Pereira MA, Ramos MFKP, Faraj SF, Dias AR, Yagi OK, Zilberstein B, et al. Clinicopathological and prognostic features of Epstein-Barr virus infection, microsatellite instability, and PD-L1 expression in gastric cancer. J Surg Oncol. 2018;117:829–39.CrossRef
Metadata
Title
Increased assessment of HER2 in metastatic gastroesophageal cancer patients: a nationwide population-based cohort study
Authors
Willemieke P. M. Dijksterhuis
Rob H. A. Verhoeven
Sybren L. Meijer
Marije Slingerland
Nadia Haj Mohammad
Judith de Vos-Geelen
Laurens V. Beerepoot
Theo van Voorthuizen
Geert-Jan Creemers
Martijn G. H. van Oijen
Hanneke W. M. van Laarhoven
Publication date
01-07-2020
Publisher
Springer Singapore
Published in
Gastric Cancer / Issue 4/2020
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-020-01039-7

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