Gemeinsame Stellungnahme der DGHO und DGVS zur Nutzenbewertung von Nivolumab (metastasiertes kolorektales Karzinom, dMMR oder MSI-H, vorbehandelte Patient*innen, Kombination mit Ipilimumab)

Inhaltsverzeichnis	Seite
1. Zusammenfassung	111
2. Einleitung	112
3. Stand des Wissens	112
4. Dossier und Bewertung von Nivolumab (Opdivo®)	113
4.1. Zweckmäßige Vergleichstherapie	113
4.2. Studien	113
4.3. Endpunkte	113
4.3.1. Mortalität	113
4.3.2. Morbidität	113
4.3.2.1. Progressionsfreie Überlebenszeit und Remissionsrate	113
4.3.2.2. Remissionsrate	113
4.3.2.3. Lebensqualität/Patient-Reported Outcome	113
4.3.2.4. Nebenwirkungen	114
4.4 Bericht des IQWiG	114
5. Klinische Bewertung des Nutzens	114
6. Ausmaß des Zusatznutzens	114
Literatur	114

Publication History

Article published online:
18 January 2022

• Literatur

• 1 Robert Koch-Institut [Hrsg.] und die Gesellschaft der epidemiologischen Krebsregister in Deutsch- land e. V. [Hrsg.]. Krebs in Deutschland 2015/2016. Berlin: 2019 12. Ausgabe. www.gekid.de
• 2 S3-Leitlinie Kolorektales Karzinom 2017. http://www.awmf.org/leitlinien/detail/ll/021-007OL.html
• 3 Kolonkarzinom. Leitlinien von DGHO, OeGHO, SGMO und SGH+SSH, Status Oktober 2018. https://www.onkopedia.com/de/onkopedia/guidelines/kolonkarzinom/@@guideline/html/index.html
• 4 Le DT, Uram JN, Wang H. et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015; 372: 2509-2520 DOI: 10.1056/NEJMoa1500596.
• 5 Le DT, Durham JN, Smith KN. et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017; 357: 409-413 DOI: 10.1126/science.aan6733.
• 6 Koopman M, Kortman GAM, Mekenkamp L. et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer 2009; 100: 266-273 DOI: 10.1038/sj.bjc.6604867.
• 7 Zlobec I, Kovac M, Erzberger P. et al. Combined analysis of specific KRAS mutation, BRAF and microsatellite instability identifies prognostic subgroups of sporadic and hereditary colorectal cancer. Int J Cancer 2010; 127: 2569-2575 DOI: 10.1002/ijc.25265.
• 8 Arnold CN, Goel A, Compton C. et al. Evaluation of microsatellite instability, hMLH1 expression and hMLH1 promoter hypermethylation in defining the MSI phenotype of colorectal cancer. Cancer Biol Ther 2004; 3: 73-78 DOI: 10.4161/cbt.3.1.590.
• 9 Goel A, Boland CR. Epigenetics of colorectal cancer. Gastroenterology 2012; 143: 1442-1460.e1 DOI: 10.1053/j.gastro.2012.09.032.
• 10 Innocenti F, Ou F-S, Qu X. et al. Mutational analysis of patients with colorectal cancer in CALGB/SWOG 80405 identifies new roles of microsatellite instability and tumor mutational burden for patient outcome. J Clin Oncol 37: 1217-1227 DOI: 10.1200/JCO.18.01798.
• 11 Overman MJ, McDermott R, Leach JL. et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol 2017; 18: 1182-1191 DOI: 10.1016/S1470- 2045(17)30422-9.
• 12 Overman MJ, Lonardi S, Wong KY. et al. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol 2018; 36: 773-779 DOI: 10.1200/JCO.2017.76.9901.
• 13 Le DT, Kim TW, Van Cutsem E. et al. Phase II open-label study of pembrolizumab in treatment- refractory, microsatellite instability–high/mismatch repair–deficient metastatic colorectal cancer: KEYNOTE-164. J Clin Oncol 2020; 38: 11-19 DOI: 10.1200/JCO.19.02107.
• 14 Cherny NI, Sullivan R, Dafni U. et al. A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European So- ciety for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Ann Oncol 2015; 26: 1547-1573 DOI: 10.1093/annonc/mdv249.
• 15 Cherny NI, Dafni U, Bogaerts J. et al. ESMO-Magnitude of Clinical Benefit Scale version1.1. Ann Oncol 2017; 28: 2340-2366 DOI: 10.1093/annonc/mdx310.
• 16 André F, Shiu KK, Kim TW. et al. Pembrolizumab in microsatellite instability-high advanced colo- rectal cancer. N Engl J Med 2020; 383: 2207-2218 DOI: 10.1056/NEJMoa2017699.
• 17 André F, Shiu KK, Kim TW. et al Final overall survival for the phase III KN177 study: Pembroli- zumab versus chemotherapy in microsatellite instability-high/mismatch repair deficient (MSI- H/dMMR) metastatic colorectal cancer (mCRC). ASCO 2021, Abstract 3500. https://meetings.asco.org/abstracts-presentations/195775
• 18 Lenz H-J, van Cutsem E, Limon ML. et al First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study. J Clin Oncol 2021; Online ahead of print. DOI: 10.1200/JCO.21.01015.