Die personalisierte Therapie beim Ovarialkarzinom

Die Behandlung des epithelialen Ovarial-, Tuben- und Peritonealkarzinoms (epithelial ovarian cancer; EOC) fußt auf 3 Säulen, die in unterschiedlichem Maße individualisierte bzw. personalisierte Medizin inkludieren:

1. die Operation, die immer personalisiert, d. h. angepasst an den Allgemeinzustand und die Reserven der Patientin, sowie individualisiert, d. h. adaptiert an das Tumorwachstum und Befallsmuster, durchgeführt wird,

2. die Chemotherapie, die bis dato nicht individualisiert bezüglich der Tumorbiologie, wohl aber angepasst an die klinische Situation zumindest in der Rezidivtherapie unter verschiedenen Regimen, wie z. B. platin- und nicht platinhaltig, ausgewählt wird und

3. die neueren zielgerichteten Substanzen, mit denen noch mehr Hoffnung auf personalisierte Medizin sowie effektivere und nebenwirkungsärmere Therapieregime für die individuelle Patientin verbunden wird.

• Literatur

• 1 Gesellschaft der epidemiologischen Krebsregister in Deutschland, Robert Koch-Institut. Krebs in Deutschland 2011/2012. 10. Ausgabe. Berlin: 2015
• 2 Leitlinienprogramm Onkologie (DGK, DGGG, AWMF). S3-Leitlinie Diagnostik, Therapie und Nachsorge maligner Ovarialtumoren (Langversion). Version 2.0 – Oktober 2016. AWMF-Registernummer: 032/035OL. Online: http://www.awmf.org/leitlinien/detailII/032-035OL.html Stand: 14.07.2017
• 3 Harter P, Hauke J, Heitz F. et al. Incidence of germline mutations in risk genes including BRCA1/2 in consecutive ovarial cancer (OC) patients (AGO TR-1). J Clin Oncol 2016; 34 (Suppl.) Abstr.. 5538
• 4 Deutsches Konsortium familiärer Brust- und Eierstockkrebs. Informationen. Online: http://www.konsortium-familiaerer-brustkrebs.de/informationen/familiaerer-brust-und-eierstockkrebs/ Stand: 14.07.2017
• 5 Trimbos B, Timmers P, Pecorelli S. et al. Surgical staging and treatment of early ovarian cancer: long-term analysis from a randomized trial. J Natl Cancer Inst 2010; 102: 982-987
• 6 du Bois A, Reuss A, Pujade-Lauraine E. et al. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: A combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials. Cancer 2009; 115: 1234-1244
• 7 du Bois A, Luck HJ, Meier W. et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 2003; 95: 1320-1329
• 8 Harter P, Sehouli J, Lorusso D. et al. LION: Lymphadenectomy in ovarian neoplasms–A prospective randomized AGO study group led gynecologic cancer intergroup trial. J Clin Oncol 2017; 35 (Suppl.) 5500-5500
• 9 Vergote I, Trope CG, Amant F. et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 2010; 363: 943-953
• 10 Kehoe S, Hook J, Nankivell M. et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet 2015; 386: 249-257
• 11 Marth C, Zeimet A, Du Bois A. Is neoadjuvant chemotherapy in ovarian cancer an excuse for insufficient surgery?. Oncology Williston Park 2011; 25: 940 942, 944
• 12 du Bois A, Marth C, Pfisterer J. et al. Neoadjuvant chemotherapy cannot be regarded as adequate routine therapy strategy of advanced ovarian cancer. Int J Gynecol Cancer 2012; 22: 182-185
• 13 Fotopoulou C, Sehouli J, Aletti G. et al. Value of neoadjuvant chemotherapy for newly diagnosed advanced ovarian cancer: a European perspective. J Clin Oncol 2017; 35: 587-590
• 14 ClinicalTrials.gov. Trial on Radical Upfront Surgery in Advanced Ovarian Cancer (TRUST). Online: https://clinicaltrials.gov/ct2/show/NCT02828618 Stand: 14.07.2017
• 15 Perren TJ, Swart AM, Pfisterer J. et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 2011; 365: 2484-2496
• 16 Burger RA, Brady MF, Bookman MA. et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011; 365: 2473-2483
• 17 du Bois A, Floquet A, Kim J-W. et al. Incorporation of pazopanib in maintenance therapy of ovarian cancer. J Clin Oncol 2014; 32: 3374-3382
• 18 du Bois A, Kristensen G, Ray-Coquard I. et al. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 2016; 17: 78-89
• 19 Grabowski JP, Harter P, Heitz F. et al. Operability and chemotherapy responsiveness in advanced low-grade serous ovarian cancer. An analysis of the AGO Study Group metadatabase. Gynecol Oncol 2016; 140: 457-462
• 20 Gershenson DM, Bodurka DC, Coleman RL. et al. Hormonal maintenance therapy for women with low-grade serous cancer of the ovary or peritoneum. J Clin Oncol 2017; 35: 1103-1111
• 21 Okamoto A, Sugiyama T, Hamano T. et al. Randomized phase III trial of paclitaxel/carboplatin (PC) versus cisplatin/irinotecan (CPT-P) as first-line chemotherapy in patients with clear cell carcinoma (CCC) of the ovary: A Japanese Gynecologic Oncology Group (JGOG)/GCIG study. J Clin Oncol 2014; 32: 5507-5507
• 22 Gore ME, Hackshaw A, Brady WE. et al. Multicentre trial of carboplatin/paclitaxel versus oxaliplatin/capecitabine, each with/without bevacizumab, as first line chemotherapy for patients with mucinous epithelial ovarian cancer (mEOC). J Clin Oncol 2015; 33: 5528-5528
• 23 Wilson MK, Pujade-Lauraine E, Aoki D. et al. Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: recurrent disease. Ann Oncol 2017; 28: 727-732
• 24 Harter P, Hahmann M, Lueck HJ. et al. Surgery for recurrent ovarian cancer: role of peritoneal carcinomatosis: exploratory analysis of the DESKTOP I Trial about risk factors, surgical implications, and prognostic value of peritoneal carcinomatosis. Ann Surg Oncol 2009; 16: 1324-1330
• 25 Harter P, Sehouli J, Reuss A. et al. Prospective validation study of a predictive score for operability of recurrent ovarian cancer: the Multicenter Intergroup Study DESKTOP II. A project of the AGO Kommission OVAR, AGO Study Group, NOGGO, AGO-Austria, and MITO. Int J Gynecol Cancer 2011; 21: 289-295
• 26 du Bois A, Vergote I, Ferron G. et al. Randomized controlled phase III study evaluating the impact of secondary cytoreductive surgery in recurrent ovarian cancer: AGO DESKTOP III/ENGOT ov20. J Clin Oncol 2017; 35 (Suppl.) 5501-5501
• 27 Aghajanian C, Blank SV, Goff BA. et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 2012; 30: 2039-2045
• 28 Pujade-Lauraine E, Hilpert F, Weber B. et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol 2014; 32: 1302-1308
• 29 Ledermann J, Harter P, Gourley C. et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 2012; 366: 1382-1392
• 30 Ledermann JA, Harter P, Gourley C. et al. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol 2016; 17: 1579-1589
• 31 Pujade-Lauraine E, Ledermann J, Selle F. et al. Olaparib tablets as maintenace therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/NGOT-Ov21): a double-blind, randomized, placebo-controlled phase 3 trial. Lancet Oncol 2017; 18: 1274-1284 . Online: http://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(17)30469-2.pdf Stand: 17.08.2017
• 32 http://www.nasdaq.com. Clovis Oncologyʼs Rucaparib Significantly Improved Progression-Free Survival in All Ovarian Cancer Patient Populations Studied in Phase 3 ARIEL3 Maintenance Treatment Trial. Online: http://www.nasdaq.com/press-release/clovisoncologys-rucaparib-significantly-improvedprogression-free-survival-in-all-ovariancancer-20170619-00122 Stand: 14.07.2017
• 33 Mirza MR, Monk BJ, Herrstedt J. et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 2016; 375: 2154-2164
• 34 ClinicalTrials.gov. Platine, Avastin and OLAparib in 1st Line (PAOLA-1). Online: https://clinicaltrials.gov/show/NCT02477644 Stand: 14.07.2017
• 35 ClinicalTrials.gov. A study of niraparib maintenance treatment in patients With advanced ovarian cancer following response on front-line platinum-based chemotherapy. Online: https://clinicaltrials.gov/ct2/show/NCT02655016 Stand: 14.07.2017
• 36 ClinicalTrials.gov. A study of atezolizumab versus placebo in combination With paclitaxel, carboplatin, and bevacizumab in participants with newly-diagnosed stage III or stage IV ovarian, fallopian tube, or primary peritoneal cancer (IMagyn050). Online: https://clinicaltrials.gov/ct2/show/NCT03038100 Stand: 14.07.2017
• 37 ClinicalTrials.gov. ATALANTE: Atezolizumab vs placebo phase III study in late relapse ovarian cancer treated with chemotherapy + bevacizumab (ATALANTE). Online: https://clinicaltrials.gov/ct2/show/NCT02891824 Stand: 14.07.2017
• 38 ClinicalTrials.gov. A study to examine olaparib maintenance retreatment in patients with epithelial ovarian cancer (OReO). Online: https://clinicaltrials.gov/ct2/show/NCT02855944 Stand: 14.07.2017
• 39 Liu JF, Barry WT, Birrer M. et al. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol 2014; 15: 1207-1214
• 40 Underhill C, Toulmonde M, Bonnefoi H. A review of PARP inhibitors: from bench to bedside. Ann Oncol 2011; 22: 268-279
• 41 Swisher EM, Lin KK, Oza AM. et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol 2017; 18: 75-87