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Z Gastroenterol 2018; 56(04): 384-397
DOI: 10.1055/s-0044-101757
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

ASCO- und ESMO-Update 2017 – Neuigkeiten vom 53. Meeting der American Society of Clinical Oncology/ASCO 2017 und European Society for Medical Oncology/ESMO-Congress 2017

ASCO- and ESMO-update 2017 – highlights of the 53. meeting of the American Society of Clinical Oncology/ASCO 2017 and European Society for Medical Oncology/ESMO congress 2017
Thomas J. Ettrich
1   Klinik für Innere Medizin, Universitätsklinikum Ulm, Ulm
,
Matthias Ebert
2   Medizinische Klinik des Universitätsklinikums Mannheim der Universität Heidelberg
,
Sylvie Lorenzen
3   Medizinische Klinik, Klinikum rechts der Isar, München
,
Markus Moehler
4   I. Medizinische Klinik und Poliklinik, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz
,
Arndt Vogel
5   Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
,
Lukas Witkowski
6   Abteilung für Hämatologie, Onkologie und Palliativmedizin, St. Josef-Hospital, Ruhr-Universität Bochum, Bochum
,
Thomas Seufferlein
1   Klinik für Innere Medizin, Universitätsklinikum Ulm, Ulm
,
Anke Reinacher-Schick
6   Abteilung für Hämatologie, Onkologie und Palliativmedizin, St. Josef-Hospital, Ruhr-Universität Bochum, Bochum
› Author Affiliations
Further Information

Publication History

08 August 2017

23 January 2018

Publication Date:
11 April 2018 (online)

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Zusammenfassung

Auf dem Amerikanischen Krebskongress 2017 und dem Europäischen Krebskongress 2017 wurden eine Reihe von wichtigen Studien vorgestellt, die teilweise zu einer Änderung der aktuellen Therapiestandards in der Viszeralonkologie führen. So gilt nach den Ergebnissen der FLOT4-Studie die Kombination aus Docetaxel, Oxaliplatin und 5-Fluorouracil (FLOT) als der neue Behandlungsstandard in der perioperativen Therapie bei resektablen Adenokarzinomen des gastroösophagealen Übergangs und des Magens. Beim hepatozellulären Karzinom (HCC) hat die selektive interne Radiotherapie (SIRT) in zwei großen Studien keine Verbesserung des Überlebens gegenüber Sorafenib erbracht, sodass ein zunehmender Einsatz der SIRT nicht empfohlen wird. Hingegen scheint der Multityrosinkinase-Inhibitor Lenvatinib eine vielversprechende Alternative zu Sorafenib beim fortgeschrittenen HCC in der Erstlinientherapie zu sein. Beim frühen Kolonkarzinom kann nach den Daten der IDEA-Initiative bei Niedrigrisiko-Tumoren (T1 – 3, N1) nun eine dreimonatige Therapie mit Capecitabin und Oxaliplatin (CAPOX) empfohlen werden. Bei Hochrisikotumoren (T4 oder N2) soll weiterhin eine sechsmonatige Therapie mit 5-FU und Oxaliplatin (FOLFOX) oder CAPOX durchgeführt werden. Neben regelmäßiger Bewegung soll auch ein regelmäßiger Verzehr von Nüssen die Rezidivrate nach Resektion eines Kolonkarzinoms senken. Beim metastasierten kolorektalen Karzinom (mKRK) hat die SIRT in der Erstlinientherapie keinen Stellenwert. Beim BRAF-mutierten mKRK stellt die Kombination von Irinotecan, Cetuximab und Vemurafenib eine gute Therapiemöglichkeit in der Zweitlinientherapie dar. In der adjuvanten Therapie von Gallenwegstumoren stellt durch die positiven Ergebnisse der BILCAP-Studie die sechsmonatige Therapie mit Capecitabin den neuen Behandlungsstandard dar. Für das metastasierte Pankreaskarzinom kann möglicherweise der gezielte Angriff auf das Tumorstroma durch pegylierte Hyaluronidase PEGPH20 eine neue Therapieoption bieten, die derzeit in Phase-III-Studien überprüft wird.

Abstract

At ASCO 2017, and subsequently the ESMO congress 2017, a number of studies were presented which, in part, may change the present standard of therapy in gastrointestinal oncology. The German FLOT4 trial established perioperative Docetaxel, Oxaliplatin and 5-Fluorouracil (5-FU) as the new treatment standard for resectable adenocarcinoma of the gastroesophageal junction and the stomach. In hepatocellular carcinoma (HCC), two large studies did not show a survival benefit for selective internal therapy (SIRT), so an increasing use of SIRT in HCC is not recommended. On the other hand, the multityrosinekinase inhibitor Lenvatinib seems to be a promising alternative to sorafenib in first line treatment of metastatic HCC. In early colon cancer—following the data from the large IDEA initiative—three months of capecitabine and oxaliplatin is recommended for low-risk stage III cancers (T1 – 3, N1), while in high-risk stage III cancers (T4 or N2) patients should still receive six months of oxaliplatin and a fluoropyrimidine. Aside from regular exercise, one study found that regular intake of tree nuts (at least 2 servings per week), may decrease the risk of recurrence. In first line metastatic colorectal cancer (mCRC), SIRT should not be applied, whereas in BRAF mutant cancers, the combination of irinotecan, cetuximab and vemurafenib seems to be a promising second line treatment option. In biliary tract cancer, after curative resection, six months of capecitabine is considered the new treatment standard. Finally, in pancreatic cancer, targeting the tumor stroma with pegylated hyaluronidase (PEGPH20) may be a new treatment option that needs to be proven in phase 3 studies.

Schlüsselwörter

Ösophaguskarzinom - Magenkarzinom - kolorektales Karzinom - Pankreaskarzinom - Leberzellkarzinom - Gallenwegskarzinom - Targeted Therapies - klinische Studien - ASCO Meeting

Key words

esophageal cancer - gastric cancer - colorectal cancer - pancreatic cancer - hepatobiliary cancer - targeted therapies - clinical trials
 

  • Literatur

  • 1 Al-Batran SE, Hofheinz RD, Pauligk C. et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. The Lancet Oncology 2016; 17: 1697-1708
    CrossrefPubMedSearch in Google Scholar
  • 2 Ruhstaller T, Thuss-Patience P, Hayoz S. et al. Intergroup phase III trial of neo-adjuvant chemotherapy, followed by chemoradiation and surgery with and without cetuximab in locally advanced esophageal carcinoma: First results from the SAKK 75/08 trial. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017 35. (suppl; abstr 4019)
    PubMedSearch in Google Scholar
  • 3 Fuchs CS, Doi T, Jang RWJ. et al. KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer. J Clin Oncol 2017 35. ; (suppl; abstr 4003)
    PubMedSearch in Google Scholar
  • 4 Catenacci DV, Fuchs CS. et al. KEYNOTE-059 cohort 3: safety and efficacy of pembrolizumab monotherapy for first-line treatment of patients (pts) with PD-L1-positive advanced gastric/gastroesophageal (G/GEJ) cancer. Ann Oncol 2017; 28 (Suppl. 03)
    CrossrefPubMedSearch in Google Scholar
  • 5 Bang Y, Fuchs CS, Golan T. et al. KEYNOTE-059 cohort 2: Safety and efficacy of pembrolizumab (pembro) plus 5-fluorouracil (5-FU) and cisplatin for first-line (1L) treatment of advanced gastric cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017 35. (suppl; abstr 4012)
    PubMedSearch in Google Scholar
  • 6 Wainberg ZA, Muro H, Yoon HH. et al. KEYNOTE-059 Update: Efficacy and safety of pembrolizumab alone or in combination with chemotherapy in patients with advanced gastric or gastroesophageal (G/GEJ) cancer. Annals of Oncology 2017 28. Issue suppl_5, 1 September 2017, mdx440.020
    PubMedSearch in Google Scholar
  • 7 Kang YK, Boku N, Satoh T. et al. 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 2017;
    CrossrefPubMedSearch in Google Scholar
  • 8 Boku N, Kang Y, Satoh T. et al. 617O A Phase 3 Study of nivolumab (Nivo) in previously treated advanced gastric or gastroesophageal junction (G/GEJ) cancer: Updated results and subset analysis by PD-L1 expression (ATTRACTION-02). Annals of Oncology 2017 28. Issue suppl_5, 1 September 2017, mdx369.001
    PubMedSearch in Google Scholar
  • 9 Janjigian YY, Calvo E, Kim JW. et al. Nivolumab ± ipilimumab in pts with advanced (adv)/metastatic chemotherapy-refractory (CTx-R) gastric (G), esophageal (E), or gastroesophageal junction (GEJ) cancer: CheckMate 032 study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017 35. (suppl; abstr 4014)
    PubMedSearch in Google Scholar
  • 10 Vilgrain V, Bouattour M, Sibert A. et al. SARAH: a randomised controlled trial comparing efficacy and safety of selective internal radiation therapy (with yttrium-90 microspheres) and sorafenib in patients with locally advanced hepatocellular carcinoma. J Hepatol 2017; 66: S85-S86
    PubMedSearch in Google Scholar
  • 11 Pierce HW, Chow MG. Asia-Paciifc Hepatocellular Carcinoma Trials Group; National Cancer Center Singapore, Singapore, Singapore; Singapore Clinical Research Insititute, Singapore, Singapore. Phase III multi-centre open-label randomized controlled trial of selective internal radiation therapy (SIRT) versus sorafenib in locally advanced hepatocellular carcinoma: The SIRveNIB study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017 35. (suppl; abstr 4002)
    PubMedSearch in Google Scholar
  • 12 Cheng AL, Qin S, Han KH. et al. Phase III trial of lenvatinib (LEN) vs sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC). Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017 35. (suppl; abstr 4001)
    PubMedSearch in Google Scholar
  • 13 Vogel A, Kudo M, Hudgens S. et al. Health-Related Quality of Life (HRQOL) and Disease Symptoms in Patients with Unresectable Hepatocellular Carcinoma (HCC) Treated with Lenvatinib (LEN) or Sorafenib (SOR). Annals of Oncology 2017 28. Issue suppl_5, 1 September 2017, mdx369.002
    PubMedSearch in Google Scholar
  • 14 Rimassa L, Peck-Radosavljevic M, Zagonel V. et al. Second-line tivantinib (ARQ 197) vs placebo in patients (Pts) with MET-high hepatocellular carcinoma (HCC): Results of the METIV-HCC phase III trial. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017 35. (suppl; abstr 4000)
    PubMedSearch in Google Scholar
  • 15 Kobayashi S, Ueshima K, Moriguchi M. et al. JET-HCC: A phase 3 randomized, double-blind, placebo-controlled study of tivantinib as a second-line therapy in patients with c-Met high hepatocellular carcinoma. Annals of Oncology 2017 28. Issue suppl_5, 1 September 2017, mdx369.003
    PubMedSearch in Google Scholar
  • 16 Crocenzi TS, Yau TC, Melero I. et al. Nivolumab (nivo) in sorafenib (sor)-naive and -experienced pts with advanced hepatocellular carcinoma (HCC): CheckMate 040 study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017 35. (suppl; abstr 4013)
    PubMedSearch in Google Scholar
  • 17 Dou R, Ng K, Giovannucci EL. et al. Vitamin D and colorectal cancer: molecular, epidemiological and clinical evidence. The British journal of nutrition 2016; 115: 1643-1660
    CrossrefPubMedSearch in Google Scholar
  • 18 Ng KNH, McCleary NJ, Abrams TA. et al. SUNSHINE: Randomized double-blind phase II trial of vitamin D supplementation in patients with previously untreated metastatic colorectal cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017 35. (suppl; abstr 3506)
    PubMedSearch in Google Scholar
  • 19 Yang M, Hu FB, Giovannucci EL. et al. Nut consumption and risk of colorectal cancer in women. European journal of clinical nutrition 2016; 70: 333-337
    CrossrefPubMedSearch in Google Scholar
  • 20 Fadelu TND, Zhang S, Ye X. et al. Nut consumption and survival in stage III colon cancer patients: Results from CALGB 89803 (Alliance). Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017 35. (suppl; abstr 3517)
    PubMedSearch in Google Scholar
  • 21 Andre T, de Gramont A, Vernerey D. et al. Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer: Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2015; 33: 4176-4187
    CrossrefPubMedSearch in Google Scholar
  • 22 Shi Q, Shields AF, Yoshino T. et al. Prospective pooled analysis of six phase III trials investigating duration of adjuvant (adjuv) oxaliplatin-based therapy (3 vs 6 months) for patients (pts) with stage III colon cancer (CC): The IDEA (International Duration Evaluation of Adjuvant chemotherapy) collaboration. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017 35. (suppl; abstr LBA1)
    PubMedSearch in Google Scholar
  • 23 Grothey A, Meyerhardt JA, Yoshino T. et al. LBA21_PR ’Prospective pooled analysis of six phase III trials investigating duration of adjuvant (adjuv) oxaliplatin-based therapy (3 vs 6 months) for patients (pts) with stage III colon cancer (CC): Updated results of IDEA (International Duration Evaluation of Adjuvant chemotherapy). Annals of Oncology 2017; 28 (Suppl. 05) v605-v649 doi:10.1093/annonc/mdx440
    PubMedSearch in Google Scholar
  • 24 Taieb J, Emile JF, Le Malicot K. et al. Association of prognostic value of primary tumor location in stage III colon cancer with RAS and BRAF mutational status. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017 35. (suppl; abstr 3515)
    PubMedSearch in Google Scholar
  • 25 Kim SR, Yothers G, Gavin P. et al. Tumor sidedness and intrinsic subtypes in patients with stage II/III colon cancer: Analysis of NSABP C-07 (NRG Oncology). Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017 35. (suppl; abstr 3514)
    PubMedSearch in Google Scholar
  • 26 Reinacher-Schick AC, Noepel-Duennebacke S, Arnold D. et al. Association of microsatellite instability with distinct clinical and molecular characteristics in resected colon cancer: Analysis of a platform trial of the AIO colorectal study group—Colopredict Plus. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017; 35 (Suppl. 15) e15086-e15086
    CrossrefPubMedSearch in Google Scholar
  • 27 Guinney J, Dienstmann R, Wang X. et al. The consensus molecular subtypes of colorectal cancer. Nature medicine 2015; 21: 1350-1356
    CrossrefPubMedSearch in Google Scholar
  • 28 Stintzing S, Wirapati P, Lenz HJ. et al. Consensus molecular subgroups (CMS) of colorectal cancer (CRC) and first-line efficacy of FOLFIRI plus cetuximab or bevacizumab in the FIRE3 (AIO KRK-0306) trial. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017 35. (suppl; abstr 3510)
    PubMedSearch in Google Scholar
  • 29 Lenz HJ, Ou FS, Venook AP. et al. Impact of consensus molecular subtyping (CMS) on overall survival (OS) and progression free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405 (Alliance). Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017 35. (suppl; abstr 3511)
    PubMedSearch in Google Scholar
  • 30 Kopetz SSLM, Lenz HJ, Magliocco AM. et al. Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG S1406). Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2017 35. (suppl; abstr 3505)
    PubMedSearch in Google Scholar
  • 31 Shin HR, Oh JK, Masuyer E. et al. Comparison of incidence of intrahepatic and extrahepatic cholangiocarcinoma--focus on East and South-Eastern Asia. Asian Pacific journal of cancer prevention: APJCP 2010; 11: 1159-1166
    PubMedSearch in Google Scholar
  • 32 Edeline J, Bonnetain F, Phelip JM. et al. Gemox versus surveillance following surgery of localized biliary tract cancer: Results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial. Journal of Clinical Oncology 2017; 35: 225-225
    CrossrefPubMedSearch in Google Scholar
  • 33 Primrose JN, Fox R, Palmer DH. et al. Adjuvant capecitabine for biliary tract cancer: The BILCAP randomized study. Journal of Clinical Oncology 2017; 35: 4006-4006
    CrossrefPubMedSearch in Google Scholar
  • 34 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
    CrossrefPubMedSearch in Google Scholar
  • 35 Whatcott CJ, Diep CH, Jiang P. et al. Desmoplasia in Primary Tumors and Metastatic Lesions of Pancreatic Cancer. Clin Cancer Res 2015; 21: 3561-3568
    CrossrefPubMedSearch in Google Scholar
  • 36 Jacobetz MA, Chan DS, Neesse A. et al. Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut 2013; 62: 112-120
    CrossrefPubMedSearch in Google Scholar
  • 37 Thompson CB, Shepard HM, O’Connor PM. et al. Enzymatic depletion of tumor hyaluronan induces antitumor responses in preclinical animal models. Mol Cancer Ther 2010; 9: 3052-3064
    CrossrefPubMedSearch in Google Scholar
  • 38 Brekken C, de Lange Davies C. Hyaluronidase reduces the interstitial fluid pressure in solid tumours in a non-linear concentration-dependent manner. Cancer Lett 1998; 131: 65-70
    CrossrefPubMedSearch in Google Scholar
  • 39 Eikenes L, Tari M, Tufto I. et al. Hyaluronidase induces a transcapillary pressure gradient and improves the distribution and uptake of liposomal doxorubicin (Caelyx) in human osteosarcoma xenografts. Br J Cancer 2005; 93: 81-88
    CrossrefPubMedSearch in Google Scholar
  • 40 Spruss T, Bernhardt G, Schonenberger H. et al. Hyaluronidase significantly enhances the efficacy of regional vinblastine chemotherapy of malignant melanoma. J Cancer Res Clin Oncol 1995; 121: 193-202
    CrossrefPubMedSearch in Google Scholar
  • 41 Hingorani SR, Bullock AJ, Seery TE. et al. Randomized phase II study of PEGPH20 plus nab-paclitaxel/gemcitabine (PAG) vs AG in patients (Pts) with untreated, metastatic pancreatic ductal adenocarcinoma (mPDA). Journal of Clinical Oncology 2017; 35: 4008-4008
    CrossrefPubMedSearch in Google Scholar
  • 42 Hingorani SR, Bullock A, Seery T. et al. 763PRandomized phase 2 study of PEGPH20 Plus nab-paclitaxel/gemcitabine (PAG) vs AG in patients (Pts) with untreated, metastatic pancreatic ductal adenocarcinoma (mPDA). Annals of Oncology 2017 28. mdx369.145-mdx369.145
    PubMedSearch in Google Scholar
  • 43 Hammel P, Bachet JB, Portales F. et al. 621PDA Phase 2b of eryaspase in combination with gemcitabine or FOLFOX as second-line therapy in patients with metastatic pancreatic adenocarcinoma (NCT02195180). Annals of Oncology 2017 28. mdx369.005-mdx369.005
    PubMedSearch in Google Scholar
  • 44 Cubillo Gracian A, Dean A, Muñoz A. et al. 620PDYOSEMITE: A 3 arm double-blind randomized phase 2 study of gemcitabine, paclitaxel protein-bound particles for injectable suspension, and placebo (GAP) versus gemcitabine, paclitaxel protein-bound particles for injectable suspension and either 1 or 2 truncated courses of demcizumab (GAD). Annals of Oncology 2017 28. mdx369.004-mdx369.004
    PubMedSearch in Google Scholar
  • 45 Philip PA, Lacy J, Portales F. et al. 622PDnab-Paclitaxel (nab-P) plus gemcitabine (G) for patients (Pts) with locally advanced pancreatic cancer (LAPC): Interim efficacy and safety results from the Phase 2 LAPACT Trial. Annals of Oncology 2017 28. mdx369.006-mdx369.006
    PubMedSearch in Google Scholar
  • 46 Reni M, Zanon S, Balzano G. et al. 736PRandomized phase 2 trial of peri- or post-operative chemotherapy in resectable pancreatic adenocarcinoma. Annals of Oncology 2017 28. mdx369.119-mdx369.119
    PubMedSearch in Google Scholar
  • 47 Hidalgo M, Pazo-Cid R, Guillen-Ponce C. et al. 623PDA phase I and randomized phase II trial to evaluate the efficacy and safety of nab-paclitaxel (nab-P) in combination with gemcitabine (G) for the treatment of patients with ECOG 2 advanced pancreatic cancer (PDAC). Annals of Oncology 2017 28. mdx369.007-mdx369.007
    PubMedSearch in Google Scholar
  • 48 Von Hoff DD, Ervin T, Arena FP. et al. Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine. New England Journal of Medicine 2013; 369: 1691-1703
    CrossrefPubMedSearch in Google Scholar