Cytoreductive surgery followed by chemotherapy and olaparib maintenance in BRCA 1/2 mutated recurrent ovarian cancer: a retrospective MITO group study

Introduction The role of cytoreductive surgery in the poly-ADP ribose polymerase inhibitors era is not fully investigated. We evaluated the impact of surgery performed prior to platinum-based chemotherapy followed by olaparib maintenance in platinum-sensitive BRCA-mutated recurrent ovarian cancer. Methods This retrospective study included platinum-sensitive recurrent ovarian cancer BRCA-mutated patients from 13 Multicenter Italian Trials in Ovarian cancer and gynecological malignancies centers treated between September 2015 and May 2019. The primary outcomes were progression-free survival and overall survival. Data on post-progression treatment was also assessed. Results Among 209 patients, 72 patients (34.5%) underwent cytoreductive surgery followed by platinum-based chemotherapy and olaparib maintenance, while 137 patients (65.5%) underwent chemotherapy treatment alone. After a median follow-up of 37.3 months (95% CI: 33.4 to 40.8), median progression-free survival in the surgery group was not reached, compared with 11 months in patients receiving chemotherapy alone (P<0.001). Median overall survival was nearly double in patients undergoing surgery before chemotherapy (55 vs 28 months, P<0.001). Post-progression therapy was assessed in 127 patients: response rate to chemotherapy was 29.2%, 8.8%, and 9.0% in patients with platinum-free interval >12 months, between 6 and 12 months, and <6 months, respectively. Conclusion Cytoreductive surgery performed before platinum therapy and olaparib maintenance was associated with longer progression-free survival and overall survival in BRCA-mutated platinum-sensitive relapsed ovarian cancer patients. In accordance with our preliminary results, the response rate to chemotherapy given after progression during olaparib was associated with platinum-free interval.

[1]  A. Oza,et al.  813MO Efficacy of subsequent chemotherapy for patients with BRCA1/2 mutated platinum-sensitive recurrent epithelial ovarian cancer (EOC) progressing on olaparib vs placebo: The SOLO2/ENGOT Ov-21 trial , 2020 .

[2]  P. Sevelda,et al.  812MO Maintenance olaparib + bevacizumab (bev) in patients (pts) with newly diagnosed advanced high-grade ovarian cancer (HGOC): RECIST and/or CA-125 objective response rate (ORR) in the phase III PAOLA-1 trial , 2020 .

[3]  A. Oza,et al.  Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial. , 2020, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  A. Oza,et al.  Overcoming Platinum and PARP-Inhibitor Resistance in Ovarian Cancer , 2020, Cancers.

[5]  A. Oza,et al.  Final overall survival (OS) results from SOLO2/ENGOT-ov21: A phase III trial assessing maintenance olaparib in patients (pts) with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation. , 2020 .

[6]  A. Reuss,et al.  Randomized phase III study to evaluate the impact of secondary cytoreductive surgery in recurrent ovarian cancer – final analysis of AGO DESKTOP III/ENGOT- ov20 , 2020, Geburtshilfe und Frauenheilkunde.

[7]  A. Jemal,et al.  Cancer statistics, 2020 , 2020, CA: a cancer journal for clinicians.

[8]  F. Marmé,et al.  Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. , 2019, The New England journal of medicine.

[9]  Danielle M. Enserro,et al.  Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer. , 2019, The New England journal of medicine.

[10]  C. Carella,et al.  Olaparib as maintenance therapy in patients with BRCA 1-2 mutated recurrent platinum sensitive ovarian cancer: Real world data and post progression outcome. , 2019, Gynecologic oncology.

[11]  G. Scambia,et al.  Secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer before olaparib maintenance: Still getting any benefit? A case-control study. , 2019, Gynecologic oncology.

[12]  B. Monk,et al.  Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. , 2019, The New England journal of medicine.

[13]  J. Griggs,et al.  Outcomes of secondary cytoreductive surgery for patients with platinum-sensitive recurrent ovarian cancer. , 2019, American journal of obstetrics and gynecology.

[14]  Gabe S. Sonke,et al.  Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer , 2018, The New England journal of medicine.

[15]  James X. Sun,et al.  Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial , 2017, The Lancet.

[16]  Val Gebski,et al.  Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. , 2017, The Lancet. Oncology.

[17]  Ignace Vergote,et al.  Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. , 2016, The New England journal of medicine.

[18]  L. Massuger,et al.  Cytoreductive surgery followed by chemotherapy versus chemotherapy alone for recurrent platinum-sensitive epithelial ovarian cancer (SOCceR trial): a multicenter randomised controlled study , 2014, BMC Cancer.

[19]  J. Huober,et al.  Surgery in Recurrent Ovarian Cancer: The Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR Trial , 2006, Annals of Surgical Oncology.

[20]  M Schemper,et al.  A note on quantifying follow-up in studies of failure time. , 1996, Controlled clinical trials.

[21]  David A. Schoenfeld,et al.  Partial residuals for the proportional hazards regression model , 1982 .

[22]  N. Spirtos,et al.  The role of secondary cytoreductive surgery in the treatment of patients with recurrent epithelial ovarian carcinoma , 2000, Cancer.