Olaparib as maintenance therapy in patients with BRCA 1-2 mutated recurrent platinum sensitive ovarian cancer: Real world data and post progression outcome

被引：81

作者：

Cecere, Sabrina Chiara ^{[1
]}

Giannone, Gaia ^{[2
,3
]}

Salutari, Vanda ^{[4
]}

Arenare, Laura ^{[5
]}

Lorusso, Domenica ^{[6
]}

Ronzino, Graziana ^{[7
]}

Lauria, Rossella ^{[8
]}

Cormio, Gennaro ^{[9
]}

Carella, Claudia ^{[10
]}

Scollo, Paolo ^{[11
]}

Ghizzoni, Viola ^{[4
]}

Raspagliesi, Francesco ^{[6
]}

Di Napoli, Marilena ^{[1
]}

Mazzoni, Enrica ^{[12
]}

Marchetti, Claudia ^{[4
,13
]}

Bergamini, Alice ^{[14
]}

Orditura, Michele ^{[15
]}

Valabrega, Giorgio ^{[2
,3
]}

Scambia, Giovanni ^{[4
]}

Maltese, Giuseppa ^{[6
]}

De Matteis, Elisabetta ^{[7
]}

Cardalesi, Cinzia ^{[8
]}

Loizzi, Vera ^{[9
]}

Boccia, Serena ^{[13
]}

Naglieri, Emanuele ^{[10
]}

Scandurra, Giuseppa ^{[11
]}

Pignata, Sandro ^{[1
]}

机构：

[1] Ist Nazl Tumori IRCCS Fdn G Pascale Napoli, Dept Urol & Gynecol, Naples, Italy

[2] FPO IRCCS, Candiolo Canc Inst, Str Provle 142,Km 3,95, I-10060 Candiolo, TO, Italy

[3] Univ Turin, Dept Oncol, Turin, Italy

[4] Fdn Policlin Univ A Gemelli, Dept Woman Child Hlth & Publ Hlth, Gynecol Oncol Unit, IRCCS, Rome, Italy

[5] Fdn G Pascale, Clin Trial Unit, IRCCS, Ist Nazl Tumori, Naples, Italy

[6] IRCCS Natl Canc Inst Fdn, Gynecol Oncol Unit, Milan, Italy

[7] Osped Vito Fazzi Lecce, Lecce, Italy

[8] Azienda Osped Univ Federico II, Div Med Oncol, Naples, Italy

[9] Univ Bari, Bari, Italy

[10] Ist Oncol Giovanni Paolo II, Gynecol Oncol Unit, Bari, Italy

[11] Cannizzaro Hosp, Med Oncol Unit, Catania, Italy

[12] Osped Senatore Antonio Perrino, Div Med Oncol, Brindisi, Italy

[13] Sapienza Univ Rome, Umberto I Hosp, Div Med Oncol, Rome, Italy

[14] IRCCS San Raffaele Hosp, Dept Obstet & Gynecol, Milan, Italy

[15] Univ Campania Luigi Vanvitelli, Oncoematol Unit, Naples, Italy

来源：

GYNECOLOGIC ONCOLOGY | 2020年 / 156卷 / 01期

关键词：

Olaparib; Maintenance; Ovarian cancer; Real world; Post progression; DOUBLE-BLIND; TUMORS; INHIBITORS; CARCINOMA; MUTATIONS; SURVIVAL; PARP;

D O I：

10.1016/j.ygyno.2019.10.023

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Objectives: Olaparib is approved as maintenance therapy in patients with BRCA mutated platinum sensitive (PS) recurrent ovarian cancer (OC) after response to last platinum based therapy. Few data are available regarding the use out of the registration trials and on response to further treatments after progression. Materials ad methods: In this non interventional, retrospective study, patients treated with olaparib in 13 centers, according to the label, have been collected and analyzed. Primary objectives of the study are to describe effectiveness and safety of olaparib in a real world setting with a focus on post progression treatments and response. Results: 234 patients were analyzed. All patients were BRCA mutated and most of them had germline mutations. Around 50% of the patients received olaparib after 3 or more lines of platinum based chemotherapy achieving a radiologic complete (CR) or partial response. 12.4% patients with stable disease were also included. Median PFS was 14.7 months (95% CI:12.6-18), with statistically longer PFS in patients with normal serum Ca125 at baseline, a CR after last platinum based therapy and that received olaparib after second platinum based therapy. Median OS was not reached. Most frequent G3-G4 toxicity was anaemia (6%) with dose discontinuation and dose reduction in 11 (4.7%) and 49 (20.9%) of cases, respectively. Among 66 patients receiving further treatment after olaparib progression and evaluable for response, ORR was 22.2, 11.1% and 9.5% in patients with Platinum Free interval (PFI) of more than 12 months, between 6 and 12 months and less than 6 months, respectively. Conclusions: Olaparib is effective and safe in real world setting. Data on post-progression treatments seem to suggest cross resistance with chemotherapy and need to be confirmed in larger studies because of the potential importance in clinical practice decisions. (C) 2019 Published by Elsevier Inc.

引用

页码：38 / 44

页数：7

共 32 条

[1] Integrated genomic analyses of ovarian carcinoma [J].

Bell, D. ;

Berchuck, A. ;

Birrer, M. ;

Chien, J. ;

Cramer, D. W. ;

Dao, F. ;

Dhir, R. ;

DiSaia, P. ;

Gabra, H. ;

Glenn, P. ;

Godwin, A. K. ;

Gross, J. ;

Hartmann, L. ;

Huang, M. ;

Huntsman, D. G. ;

Iacocca, M. ;

Imielinski, M. ;

Kalloger, S. ;

Karlan, B. Y. ;

Levine, D. A. ;

Mills, G. B. ;

Morrison, C. ;

Mutch, D. ;

Olvera, N. ;

Orsulic, S. ;

Park, K. ;

Petrelli, N. ;

Rabeno, B. ;

Rader, J. S. ;

Sikic, B. I. ;

Smith-McCune, K. ;

Sood, A. K. ;

Bowtell, D. ;

Penny, R. ;

Testa, J. R. ;

Chang, K. ;

Dinh, H. H. ;

Drummond, J. A. ;

Fowler, G. ;

Gunaratne, P. ;

Hawes, A. C. ;

Kovar, C. L. ;

Lewis, L. R. ;

Morgan, M. B. ;

Newsham, I. F. ;

Santibanez, J. ;

Reid, J. G. ;

Trevino, L. R. ;

Wu, Y. -Q. ;

Wang, M. .

NATURE, 2011, 474 (7353) :609-615

[2] Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase [J].

Bryant, HE ;

Schultz, N ;

Thomas, HD ;

Parker, KM ;

Flower, D ;

Lopez, E ;

Kyle, S ;

Meuth, M ;

Curtin, NJ ;

Helleday, T .

NATURE, 2005, 434 (7035) :913-917

[3] Treatment of patients with recurrent epithelial ovarian cancer for whom platinum is still an option [J].

Buechel, M. ;

Herzog, T. J. ;

Westin, S. N. ;

Coleman, R. L. ;

Monk, B. J. ;

Moore, K. N. .

ANNALS OF ONCOLOGY, 2019, 30 (05) :721-732

[4] Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial [J].

Coleman, Robert L. ;

Oza, Amit M. ;

Lorusso, Domenico ;

Aghajanian, Carol ;

Oaknin, Ana ;

Dean, Andrew ;

Colombo, Nicoletta ;

Weberpals, Johanne, I ;

Clamp, Andrew ;

Scambia, Giovanni ;

Leary, Alexandra ;

Holloway, Robert W. ;

Amenedo Gancedo, Margarita ;

Fong, Peter C. ;

Goh, Jeffrey C. ;

O'Malley, David M. ;

Armstrong, Deborah K. ;

Garcia-Donas, Jesus ;

Swisher, Elizabeth M. ;

Floquet, Anne ;

Konecny, Gottfried E. ;

McNeish, lain A. ;

Scott, Clare L. ;

Cameron, Terri ;

Maloney, Lara ;

Isaacson, Jeff ;

Goble, Sandra ;

Grace, Caroline ;

Harding, Thomas C. ;

Raponi, Mitch ;

Sun, James ;

Lin, Kevin K. ;

Giordano, Heidi ;

Ledermann, Jonathan A. .

LANCET, 2017, 390 (10106) :1949-1961

[5] ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease [J].

Colombo, N. ;

Sessa, C. ;

du Bois, A. ;

Ledermann, J. ;

McCluggage, W. G. ;

McNeish, I. ;

Morice, P. ;

Pignata, S. ;

Ray-Coquard, I. ;

Vergote, I. ;

Baert, T. ;

Belaroussi, I. ;

Dashora, A. ;

Olbrecht, S. ;

Planchamp, F. ;

Querleu, D. ;

Banerjee, S. ;

Blecharz, P. ;

Bruchim, I. ;

Cibula, D. ;

Concin, N. ;

Davidson, B. ;

Devouassoux-Shisheboran, M. ;

Ferrero, A. ;

Glasspool, R. ;

Gonzalez-Martin, A. ;

Heinzelmann-Schwarz, V. ;

Joly, F. ;

Kim, J. W. ;

Kridelka, F. ;

Lorusso, D. ;

Mahner, S. ;

Mikami, M. ;

Mirza, M. R. ;

Nicum, S. ;

O'Donnell, D. M. ;

Pautier, P. ;

Rodolakis, A. ;

Sehouli, J. ;

Selcukbiricik, F. ;

Singh, N. ;

Tan, D. S. P. ;

Timmerman, D. ;

Tognon, G. ;

van der Velden, J. ;

Witteveen, P. O. ;

Zeimet, A. G. .

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 2019, 29 (04) :728-760

[6]

De La Motte Rouge T, EUR J CANCER, pS548

[7] Real-world evidence in the treatment of ovarian cancer [J].

Eisenhauer, E. A. .

ANNALS OF ONCOLOGY, 2017, 28 :61-65

[8] New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) [J].

Eisenhauer, E. A. ;

Therasse, P. ;

Bogaerts, J. ;

Schwartz, L. H. ;

Sargent, D. ;

Ford, R. ;

Dancey, J. ;

Arbuck, S. ;

Gwyther, S. ;

Mooney, M. ;

Rubinstein, L. ;

Shankar, L. ;

Dodd, L. ;

Kaplan, R. ;

Lacombe, D. ;

Verweij, J. .

EUROPEAN JOURNAL OF CANCER, 2009, 45 (02) :228-247

[9] Real-World Use and Outcomes of Olaparib: a Population-Based Cohort Study [J].

Eriksson, Irene ;

Wettermark, Bjorn ;

Bergfeldt, Kjell .

TARGETED ONCOLOGY, 2018, 13 (06) :725-733

[10] Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy [J].

Farmer, H ;

McCabe, N ;

Lord, CJ ;

Tutt, ANJ ;

Johnson, DA ;

Richardson, TB ;

Santarosa, M ;

Dillon, KJ ;

Hickson, I ;

Knights, C ;

Martin, NMB ;

Jackson, SP ;

Smith, GCM ;

Ashworth, A .

NATURE, 2005, 434 (7035) :917-921

← 1 2 3 4 →