Dauerhafte Remission unter dualer HER2-Blockade mit Trastuzumab und Pertuzumab bei metastasiertem Gallenblasenkarzinom

Zusammenfassung

Gallenblasenkarzinome stellen eine seltene, aber aggressive Tumorerkrankung dar. Der einzige kurative Ansatz besteht in der chirurgischen Resektion, jedoch kommt es häufig zu einem Rezidiv der Tumorerkrankung. Die Kombinationschemotherapie aus Cisplatin und Gemcitabin führte im lokal fortgeschrittenen oder metastasierten Stadium zu einem Überlebensvorteil gegenüber einer Gemcitabin-Monotherapie, es gibt jedoch keine anerkannte Zweitlinientherapie bei Progress. Wir berichten über eine junge Patientin mit frühem Rezidiv eines Gallenblasenkarzinoms mit kutaner und peritonealer Metastasierung, bei der durch Exomsequenzierung im Rahmen des NCT MASTER (Molecularly Aided Stratification for Tumor Eradication Research)-Programms eine Amplifikation des ERBB2-Gens mit daraus resultierender Überexpression von HER2 in den Tumorzellen festgestellt wurde. Da das Rezidiv unter der additiven Chemotherapie mit Oxaliplatin und Gemcitabin aufgetreten war, wurde die Patientin mit einer zielgerichteten Therapie mit dualer HER2-Blockade in Kombination mit nab-Paclitaxel behandelt. Mit diesem Behandlungsregime konnte eine Remission erreicht werden, die mittlerweile seit mehr als einem Jahr andauert. Dieser Fallbericht verdeutlicht das Potenzial einer auf molekularen Veränderungen basierenden Therapie von Gallenwegskarzinomen und den Bedarf für entsprechende klinische Studien.

Abstract

Gallbladder cancer represents a rare but dismal disease. The only curative option is complete surgical resection, though patients often develop recurrent disease. In patients with advanced biliary tract cancer, the combination of cisplatin and gemcitabine showed a benefit in overall survival compared to gemcitabine alone. However, there is no standardized second-line regimen after treatment failure. We report on a young patient with early recurrence of a gallbladder cancer with cutaneous and peritoneal metastases. Upon identification of an ERBB2 gene amplification within the NCT MASTER (Molecularly Aided Stratification for Tumor Eradication Research) exome sequencing program with resulting overexpression of HER2 in the tumors cells, the patient received a targeted therapy with the HER2 antibodies pertuzumab and trastuzumab in combination with nab-paclitaxel, which led to a durable remission for more than one year. This case report underlines the potential of molecularly aided personalized targeted therapy for patients with biliary tract cancer and the need for respective clinical trials.

Schlüsselwörter

Gallenwegskarzinome - Gallenblasenkarzinom - HER2 - Pertuzumab - Trastuzumab

Key words

biliary tract cancer - gall bladder cancer - HER2 - Pertuzumab - Trastuzumab

• Literatur

• 1 Hundal R, Shaffer EA. Gallbladder cancer: epidemiology and outcome. Clinical epidemiology 2014; 6: 99-109
• 2 Kanthan R, Senger JL, Ahmed S et al. Gallbladder Cancer in the 21st Century. Journal of oncology 2015; 2015: 967472
• 3 Horgan AM, Amir E, Walter T et al. Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2012; 30: 1934-1940
• 4 Stein A, Arnold D, Bridgewater J et al. Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial) – a randomized, multidisciplinary, multinational phase III trial. BMC cancer 2015; 15: 564
• 5 Valle J, Wasan H, Palmer DH et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. The New England journal of medicine 2010; 362: 1273-1281
• 6 Lamarca A, Hubner RA, David Ryder W et al. Second-line chemotherapy in advanced biliary cancer: a systematic review. Annals of oncology: official journal of the European Society for Medical Oncology/ESMO 2014; 25: 2328-2338
• 7 Razumilava N, Gores GJ. Building a staircase to precision medicine for biliary tract cancer. Nature genetics 2015; 47: 967-968
• 8 Nakamura H, Arai Y, Totoki Y et al. Genomic spectra of biliary tract cancer. Nature genetics 2015; 47: 1003-1010
• 9 Merla A, Liu KG, Rajdev L. Targeted Therapy in Biliary Tract Cancers. Current treatment options in oncology 2015; 16: 48
• 10 Roa I, de Toro G, Schalper K et al. Overexpression of the HER2/neu Gene: A New Therapeutic Possibility for Patients With Advanced Gallbladder Cancer. Gastrointestinal cancer research: GCR 2014; 7: 42-48
• 11 Kawamoto T, Krishnamurthy S, Tarco E et al. HER Receptor Family: Novel Candidate for Targeted Therapy for Gallbladder and Extrahepatic Bile Duct Cancer. Gastrointestinal cancer research: GCR 2007; 1: 221-227
• 12 Kumari N, Kapoor VK, Krishnani N et al. Role of C-erbB2 expression in gallbladder cancer. Indian journal of pathology & microbiology 2012; 55: 75-79
• 13 Kim HJ, Yoo TW, Park DI et al. Gene amplification and protein overexpression of HER-2/neu in human extrahepatic cholangiocarcinoma as detected by chromogenic in situ hybridization and immunohistochemistry: its prognostic implication in node-positive patients. Annals of oncology: official journal of the European Society for Medical Oncology/ESMO 2007; 18: 892-897
• 14 Nakazawa K, Dobashi Y, Suzuki S et al. Amplification and overexpression of c-erbB-2, epidermal growth factor receptor, and c-met in biliary tract cancers. The Journal of pathology 2005; 206: 356-365
• 15 Pignochino Y, Sarotto I, Peraldo-Neia C et al. Targeting EGFR/HER2 pathways enhances the antiproliferative effect of gemcitabine in biliary tract and gallbladder carcinomas. BMC cancer 2010; 10: 631
• 16 Arteaga CL, Sliwkowski MX, Osborne CK et al. Treatment of HER2-positive breast cancer: current status and future perspectives. Nature reviews Clinical oncology 2012; 9: 16-32
• 17 Swain SM, Baselga J, Kim SB et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. The New England journal of medicine 2015; 372: 724-734
• 18 Bang YJ, 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: 687-697
• 19 Law LY. Dramatic response to trastuzumab and paclitaxel in a patient with human epidermal growth factor receptor 2-positive metastatic cholangiocarcinoma. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2012; 30: e271-e273
• 20 Sorscher S. Marked radiographic response of a HER-2-overexpressing biliary cancer to trastuzumab. Cancer Manag Res 2013; 9: 1-3
• 21 Von Hoff DD, Ervin T, Arena FP et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. The New England journal of medicine 2013; 369: 1691-1703
• 22 Javle M, Churi C, Kang HC et al. HER2/neu-directed therapy for biliary tract cancer. Journal of hematology & oncology 2015; 8: 58
• 23 Chan E, Berlin J. Biliary tract cancers: understudied and poorly understood. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2015; 33: 1845-1848