Research ArticleClinical Studies

Response to Chemotherapy and Clinical Outcome of Patients With Recurrent Epithelial Ovarian Cancer After PARP Inhibitor Maintenance Treatment: A Multicenter Retrospective Italian Study

ANGIOLO GADDUCCI, STEFANIA COSIO, FABIO LANDONI, ANDREA ALBERTO LISSONI, PAOLO ZOLA, MARIA ELENA LAUDANI, ANTONIO ARDIZZOIA, ANGELA GAMBINO and ENRICO SARTORI
Anticancer Research April 2022, 42 (4) 2017-2022; DOI: https://doi.org/10.21873/anticanres.15681

Abstract

Background/Aim: To assess response rates and survival in patients with recurrent platinum-sensitive epithelial ovarian cancer (EOC) who received PARP inhibitor (PARP-i) maintenance and who subsequently underwent salvage chemotherapy for disease progression after PARPi. Patients and Methods: This retrospective investigation analyzed 103 patients who were treated in five Italian Gynecologic centers. The PARPi used was olaparib in 46 patients, niraparib in 55, and rucaparib in 2. The interval time between the last cycle of pre- PARPi platinum–based chemotherapy and the diagnosis of progression during PARPi maintenance was defined as platinum–free interval (PFI). Results: Of the 28 patients with PFI <6 months, 23 received chemotherapy (non-platinum single agent, 20; trabectedin + pegylated liposomal doxorubicin (PLD), 3). Forty-two of the 43 patients with PFI 6-12 months underwent chemotherapy (platinum–based chemotherapy,11; trabectedin + PLD, 10; non platinum–single agent, 21). Thirty-one of the 32 patients with PFI >12 months received chemotherapy (platinum-based chemotherapy, 23; trabectedin + PLD, 3; non platinum – single agent, 5). An objective response was found in 13.0%, 26.2% and 41.9 % of the patients with PFI <6 months, 6-12 months, and >12 months (p= 0.03), respectively, and the corresponding median survivals after PARPi were 8.9 months, 17.5 months and 24.1 months (p= 0.002), respectively. Conclusion: Before the PARPi era, some randomized trials on platinum rechallenge in patients with recurrent EOC after more than 6 months from the last platinum cycle have shown response rates ranging from 47.2% to 66%. Response rates to chemotherapy for progression after PARPi appear to be lower than those expected according to PFI.

Key Words:

Poly(ADP-ribose) (PAR) polymerase (PARP) inhibitors (PARPi) are widely used as maintenance treatment after platinum-based chemotherapy in patients with platinum-sensitive recurrent epithelial ovarian cancer (EOC) (1–6). Randomized placebo-controlled trials in this clinical setting have shown that olaparib significantly improved the progression free survival (PFS) of patients with mutated BRCA EOC with hazard ratio (HR)s ranging from 0.18 [95% confidence interval (CI)=0.10-0.31] to 0.30 (95%CI=0.22-0.41) (2, 3), whereas niraparib and rucaparib significantly improved PFS regardless of either BRCA status or homologous recombination status (4, 6). However, the HR for the risk of progression associated with niraparib ranged from 0.27 (95%CI=0.17-0.41) for BRCA-mutated patients to 0.38 (95%CI=0.24-0.59) for non-BRCA mutated patients with homologous recombination deficiency to 0.45 (95%CI=0.34-0.61) for the overall non-BRCA cohort (4), and similarly the HR for the risk of progression associated with rucaparib was 0.23 (95%CI=0.16-0.34) for BRCA-mutated patients, 0.32 (95%CI=0.24-0.42) for patients with homologous recombination deficiency, and 0.36 (95%CI=0.30-0.45) for intention to treat population (6). Approximately, 15-20% of patients with platinum-sensitive recurrent EOC experienced a long-term response to PARPi lasting at least two years (7, 8). However, the patients who recur after PARPi appear to be less sensitive to further therapy (9, 10).

This retrospective multicenter investigation assessed the response to subsequent chemotherapy and the clinical outcome of patients with EOC who progressed after PARPi given as maintenance treatment after response to platinum re-challenge for platinum-sensitive recurrent disease.

Patients and Methods

This retrospective study was conducted on 103 patients who i) underwent surgery and platinum-based chemotherapy for primary FIGO stage IIB-IV EOC; ii) received one or more lines of platinum-based chemotherapy for recurrent platinum-sensitive disease; iii) received at least 3 cycles of PARPi maintenance treatment after partial or complete response to the last platinum-based chemotherapy; and iv) subsequently underwent additional treatment for disease progression at the Departments of Gynecology and Obstetrics of the Universities of Pisa, Brescia, Milano (Monza) and Torino (Mauriziano Hospital), and the Division of Medical Oncology of Lecco Hospital between 2011 and 2019.

The hospital records, including surgical notes, pathological reports, chemotherapy and follow-up data, were collected using a common form with standardized items and a common database. The tumor stage and histological diagnosis of each case were determined according to the FIGO criteria and the histological typing system of the World Health Organization (WHO), respectively. The baseline characteristics (age, FIGO stage, histological type, tumor grade, presence or absence of ascites, germline and/or somatic BRCA1-2 status, timing of surgery (primary versus interval debulking), residual disease after surgery, and type of first-line chemotherapy were reported for each case. After completion of primary treatment, all the patients were followed-up at regular scheduled intervals with the modalities reported in a previous study (11). Only the patients with clinical and/or radiological evidence of relapse were included in the present analysis. The sites of recurrence and the chemotherapy regimens for recurrence after PARPi were reported for each patient. Median follow-up of survivors was 14,7 months (range=3.0-30.5 months).

Statistical analysis. IBM SPSS Statistics (Chicago, IL, USA) was used for computations. The interval between the last cycle of platinum–based chemotherapy before PARPi maintenance treatment for recurrent disease and the clinical and/or radiological diagnosis of progression during PARPi maintenance was defined as platinum–free interval (PFI). The interval between the diagnosis of progression during PARPi maintenance and death or last follow-up was defined as survival after PARPi. Response rate to chemotherapy after PARPi was correlated with PFI using Pearson’s Chi square test (or two-tailed Fisher’s exact test when appropriate). The cumulative probability of survival after PARPi was estimated by the product-limit method and the log-rank test was used to compare the survival by PFI.

Results

Table I and Table II show patient characteristics at presentation and at disease progression after PARPi maintenance treatment, respectively. The PARPi used was olaparib in 46 patients (all with mutated-BRCA), niraparib in 55 (54 with wild-type BRCA, one with mutated-BRCA) and rucaparib in two (both with wild-type BRCA). As shown in Table III, of the 28 patients with PFI <6 months, 23 received chemotherapy, consisting of non-platinum single agent in 20 (87.0%) and trabectedin + pegylated liposomal doxorubicin (PLD) in 3 (13.0%). Forty-two of the 43 patients with PFI between 6 and 12 months underwent chemotherapy, consisting of platinum–based chemotherapy in 11 (26.2%), trabectedin + PLD in 10 (23.8%) and non-platinum single agent in 21 (50.0%). Thirty-one of the 32 patients with PFI >12 months received chemotherapy, consisting of platinum-based chemotherapy in 23 (74.2%), trabectedin + PLD in 3 (9.7%), and non-platinum single agent in 5 (16.1%).

View this table:
Table I.

Patient characteristics at presentation.

View this table:
Table II.

Patient characteristics at the time of progression after PARP inhibitor (PARPi) maintenance.

View this table:
Table III.

Chemotherapy regimens after PARP inhibitor (PARPi) according to PFI.

An objective response of 13.0%, 26.2% and 41.9% of patients with PFI <6 months, between 6 and 12 months, and >12 months (p= 0.03), respectively, was found (Table IV). Survival after PARPi is reported in Table V. Median survival after PARPi was 8.9 months, 17.5 months and 24.1 months (p= 0.002), respectively, for patients with a PFI <6 months, between 6 and 12 months, and >12 months.

View this table:
Table IV.

Response to chemotherapy in patients who recurred after PARP inhibitor (PARPi).

View this table:
Table V.

Survival in patients who recurred after PARP inhibitor (PARPi).

Discussion

Before the PARPi era, some randomized trials on platinum rechallenge in patients with recurrent EOC after more than 6 months from last platinum cycle have shown response rates ranging from 47.2% to 66% (12–16). PARPi maintenance significantly improves PFS in patients responsive to platinum re-treatment (1–6), but pharmacological mechanisms of resistance could reduce the sensitivity to further chemotherapy for tumor progression after PARPi (17–25). In particular, secondary reversion mutations of BRCA, and more rarely of RAD 51, can induce a genetic frameshift and restore the open reading frame of the genes, thus leading to expression of functional proteins, rendering tumors homologous recombination proficient and enhancing the resistance to both PARPi and platinum-based chemotherapy (23–28).

An Italian retrospective study conducted by Cecere et al. (9) analyzed the response rates to additional chemotherapy in 66 patients with BRCA-mutated EOC who relapsed following olaparib maintenance after one or more lines of platinum-based therapies Salvage treatment consisted mainly of platinum–based chemotherapy in the patients with PFI >12 months, either platinum-based chemotherapy or trabectedin ±PLD in those with PFI of 6-12 months, and non-platinum single agent in those with PFI <6 months. The response rates were 9.5%, 11.1% and 22.2% in patients with PFI <6 months, 6-12 months, and >12 months, respectively, and therefore they were lower than expected according to PFI.

The phase 3 SOLO2 trial that enrolled 295 platinum-sensitive, relapsed BRCA-mutated EOC patients in complete or partial response to their most recent platinum-based regimen, showed that olaparib maintenance provided a significant PFS improvement with no detrimental effect on quality of life (3). Recently, Frenel et al. (10) assessed women who failed after PARPi or placebo. Subsequent chemotherapy was platinum-based in 63% of the patients of the olaparib arm and in 56% of those of the placebo arm. Time to subsequent progression was longer in the placebo arm compared to olaparib arm in the whole series (HR=2.17; 95%CI=1.47-3.19) and even more in the patients who received salvage platinum-based chemotherapy (HR=2.89; 95%CI=1.73-4.82).

In the present retrospective multicenter study, that included both patients with mutant-BRCA and those with wild-type BRCA, response rates to chemotherapy for progression after PARPi were 41.9% and 26.2% in patients with PFI >12 months and between 6 and 12 months, respectively, and the corresponding 2-year PFS rates were 57.3% and 47.3%, respectively. These response rates were better than those reported by Cecere et al. (9) (11.1-22.2%), but worse than those reported with platinum re-treatment before the PARPi era (47.2%-66%) (12–16). In any case some degree of resistance to subsequent chemotherapy can occur in patients who recur after PARPi maintenance. The strengths of the study are the relatively large number of patients and the fact that patient information was collected using a common form with standardized items and a common database, whereas the weaknesses of the investigation are represented by its retrospective nature, by the different PARPi used and by the different salvage chemotherapy regimens administered after PARPi. Multicenter studies on larger series of patients, stratified for BRCA status and chemotherapy regimens used after PARPi, are strongly recommended to better define the clinical and biological behavior of recurrent EOC after PARPi.

Footnotes

  • Authors’ Contributions

    Study concepts: AG; Study design: AG, Recruitment and quality control of data: SC, AAL, MEL, AA, AGambino. Data analysis and interpretation: AG, FL, AAL, PZ, ES; Statistical analysis: AG, SC; Article preparation: AG; Article editing: All Authors; Article review: All Authors.

  • Conflicts of Interest

    The Authors declare no conflicts of interest regarding this study.

  • Received February 7, 2022.
  • Revision received February 21, 2022.
  • Accepted March 2, 2022.

References

  1. ↵
    1. Ledermann J,
    2. Harter P,
    3. Gourley C,
    4. Friedlander M,
    5. Vergote I,
    6. Rustin G,
    7. Scott C,
    8. Meier W,
    9. Shapira-Frommer R,
    10. Safra T,
    11. Matei D,
    12. Macpherson E,
    13. Watkins C,
    14. Carmichael J and
    15. Matulonis U
    : Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 366(15): 1382-1392, 2012. PMID: 22452356. DOI: 10.1056/NEJMoa1105535
    OpenUrlCrossRefPubMed
  2. ↵
    1. Ledermann J,
    2. Harter P,
    3. Gourley C,
    4. Friedlander M,
    5. Vergote I,
    6. Rustin G,
    7. Scott CL,
    8. Meier W,
    9. Shapira-Frommer R,
    10. Safra T,
    11. Matei D,
    12. Fielding A,
    13. Spencer S,
    14. Dougherty B,
    15. Orr M,
    16. Hodgson D,
    17. Barrett JC and
    18. Matulonis U
    : Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol 15(8): 852-861, 2014. PMID: 24882434. DOI: 10.1016/S1470-2045(14)70228-1
    OpenUrlCrossRefPubMed
  3. ↵
    1. Pujade-Lauraine E,
    2. Ledermann JA,
    3. Selle F,
    4. Gebski V,
    5. Penson RT,
    6. Oza AM,
    7. Korach J,
    8. Huzarski T,
    9. Poveda A,
    10. Pignata S,
    11. Friedlander M,
    12. Colombo N,
    13. Harter P,
    14. Fujiwara K,
    15. Ray-Coquard I,
    16. Banerjee S,
    17. Liu J,
    18. Lowe ES,
    19. Bloomfield R,
    20. Pautier P and SOLO2/ENGOT-Ov21 investigators
    : 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. Lancet Oncol 18(9): 1274-1284, 2017. PMID: 28754483. DOI: 10.1016/S1470-2045(17)30469-2
    OpenUrlCrossRefPubMed
  4. ↵
    1. Mirza MR,
    2. Monk BJ,
    3. Herrstedt J,
    4. Oza AM,
    5. Mahner S,
    6. Redondo A,
    7. Fabbro M,
    8. Ledermann JA,
    9. Lorusso D,
    10. Vergote I,
    11. Ben-Baruch NE,
    12. Marth C,
    13. Mądry R,
    14. Christensen RD,
    15. Berek JS,
    16. Dørum A,
    17. Tinker AV,
    18. du Bois A,
    19. González-Martín A,
    20. Follana P,
    21. Benigno B,
    22. Rosenberg P,
    23. Gilbert L,
    24. Rimel BJ,
    25. Buscema J,
    26. Balser JP,
    27. Agarwal S,
    28. Matulonis UA and ENGOT-OV16/NOVA Investigators
    : Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 375(22): 2154-2164, 2016. PMID: 27717299. DOI: 10.1056/NEJMoa1611310
    OpenUrlCrossRefPubMed
    1. Swisher EM,
    2. Lin KK,
    3. Oza AM,
    4. Scott CL,
    5. Giordano H,
    6. Sun J,
    7. Konecny GE,
    8. Coleman RL,
    9. Tinker AV,
    10. O’Malley DM,
    11. Kristeleit RS,
    12. Ma L,
    13. Bell-McGuinn KM,
    14. Brenton JD,
    15. Cragun JM,
    16. Oaknin A,
    17. Ray-Coquard I,
    18. Harrell MI,
    19. Mann E,
    20. Kaufmann SH,
    21. Floquet A,
    22. Leary A,
    23. Harding TC,
    24. Goble S,
    25. Maloney L,
    26. Isaacson J,
    27. Allen AR,
    28. Rolfe L,
    29. Yelensky R,
    30. Raponi M and
    31. McNeish IA
    : Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol 18(1): 75-87, 2017. PMID: 27908594. DOI: 10.1016/S1470-2045(16)30559-9
    OpenUrlCrossRefPubMed
  6. ↵
    1. Coleman RL,
    2. Oza AM,
    3. Lorusso D,
    4. Aghajanian C,
    5. Oaknin A,
    6. Dean A,
    7. Colombo N,
    8. Weberpals JI,
    9. Clamp A,
    10. Scambia G,
    11. Leary A,
    12. Holloway RW,
    13. Gancedo MA,
    14. Fong PC,
    15. Goh JC,
    16. O’Malley DM,
    17. Armstrong DK,
    18. Garcia-Donas J,
    19. Swisher EM,
    20. Floquet A,
    21. Konecny GE,
    22. McNeish IA,
    23. Scott CL,
    24. Cameron T,
    25. Maloney L,
    26. Isaacson J,
    27. Goble S,
    28. Grace C,
    29. Harding TC,
    30. Raponi M,
    31. Sun J,
    32. Lin KK,
    33. Giordano H,
    34. Ledermann JA and ARIEL3 investigators
    : Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390(10106): 1949-1961, 2017. PMID: 28916367. DOI: 10.1016/S0140-6736(17)32440-6
    OpenUrlCrossRefPubMed
  7. ↵
    1. Lheureux S,
    2. Lai Z,
    3. Dougherty BA,
    4. Runswick S,
    5. Hodgson DR,
    6. Timms KM,
    7. Lanchbury JS,
    8. Kaye S,
    9. Gourley C,
    10. Bowtell D,
    11. Kohn EC,
    12. Scott C,
    13. Matulonis U,
    14. Panzarella T,
    15. Karakasis K,
    16. Burnier JV,
    17. Gilks CB,
    18. O’Connor MJ,
    19. Robertson JD,
    20. Ledermann J,
    21. Barrett JC,
    22. Ho TW and
    23. Oza AM
    : Long-term responders on olaparib maintenance in high-grade serous ovarian cancer: clinical and molecular characterization. Clin Cancer Res 23(15): 4086-4094, 2017. PMID: 28223274. DOI: 10.1158/1078-0432.CCR-16-2615
    OpenUrlAbstract/FREE Full Text
  8. ↵
    1. Mirza MR,
    2. Benigno B,
    3. Dørum A,
    4. Mahner S,
    5. Bessette P,
    6. Barceló IB,
    7. Berton-Rigaud D,
    8. Ledermann JA,
    9. Rimel BJ,
    10. Herrstedt J,
    11. Lau S,
    12. du Bois A,
    13. Herráez AC,
    14. Kalbacher E,
    15. Buscema J,
    16. Lorusso D,
    17. Vergote I,
    18. Levy T,
    19. Wang P,
    20. de Jong FA,
    21. Gupta D and
    22. Matulonis UA
    : Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial. Gynecol Oncol 159(2): 442-448, 2020. PMID: 32981695. DOI: 10.1016/j.ygyno.2020.09.006
    OpenUrlCrossRefPubMed
  9. ↵
    1. Cecere SC,
    2. Giannone G,
    3. Salutari V,
    4. Arenare L,
    5. Lorusso D,
    6. Ronzino G,
    7. Lauria R,
    8. Cormio G,
    9. Carella C,
    10. Scollo P,
    11. Ghizzoni V,
    12. Raspagliesi F,
    13. Di Napoli M,
    14. Mazzoni E,
    15. Marchetti C,
    16. Bergamini A,
    17. Orditura M,
    18. Valabrega G,
    19. Scambia G,
    20. Maltese G,
    21. De Matteis E,
    22. Cardalesi C,
    23. Loizzi V,
    24. Boccia S,
    25. Naglieri E,
    26. Scandurra G and
    27. Pignata S
    : Olaparib as maintenance therapy in patients with BRCA 1-2 mutated recurrent platinum sensitive ovarian cancer: Real world data and post progression outcome. Gynecol Oncol 156(1): 38-44, 2020. PMID: 31699415. DOI: 10.1016/j.ygyno.2019.10.023
    OpenUrlCrossRefPubMed
  10. ↵
    1. Frenel J,
    2. Kim J,
    3. Berton-Rigaud D,
    4. Asher R,
    5. Vidal L,
    6. Pautier P,
    7. Ledermann J,
    8. Penson R,
    9. Oza A,
    10. Korach J,
    11. Huzarski T,
    12. Pignata S,
    13. Colombo N,
    14. Park-Simon T,
    15. Tamura K,
    16. Sonke G,
    17. Freimund A,
    18. Lee C and
    19. Pujade-Lauraine E
    : 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. Annals of Oncology 31: S615, 2021. DOI: 10.1016/j.annonc.2020.08.952
    OpenUrlCrossRef
  11. ↵
    1. Gadducci A,
    2. Fuso L,
    3. Cosio S,
    4. Landoni F,
    5. Maggino T,
    6. Perotto S,
    7. Sartori E,
    8. Testa A,
    9. Galletto L and
    10. Zola P
    : Are surveillance procedures of clinical benefit for patients treated for ovarian cancer?: A retrospective Italian multicentric study. Int J Gynecol Cancer 19(3): 367-374, 2009. PMID: 19407561. DOI: 10.1111/IGC.0b013e3181a1cc02
    OpenUrlAbstract/FREE Full Text
  12. ↵
    1. Parmar MK,
    2. Ledermann JA,
    3. Colombo N,
    4. du Bois A,
    5. Delaloye JF,
    6. Kristensen GB,
    7. Wheeler S,
    8. Swart AM,
    9. Qian W,
    10. Torri V,
    11. Floriani I,
    12. Jayson G,
    13. Lamont A,
    14. Tropé C and ICON and AGO Collaborators
    : Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet 361(9375): 2099-2106, 2003. PMID: 12826431. DOI: 10.1016/s0140-6736(03)13718-x
    OpenUrlCrossRefPubMed
    1. Pfisterer J,
    2. Plante M,
    3. Vergote I,
    4. du Bois A,
    5. Hirte H,
    6. Lacave AJ,
    7. Wagner U,
    8. Stähle A,
    9. Stuart G,
    10. Kimmig R,
    11. Olbricht S,
    12. Le T,
    13. Emerich J,
    14. Kuhn W,
    15. Bentley J,
    16. Jackisch C,
    17. Lück HJ,
    18. Rochon J,
    19. Zimmermann AH,
    20. Eisenhauer E, AGO-OVAR., NCIC CTG. and EORTC GCG
    : Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J Clin Oncol 24(29): 4699-4707, 2006. PMID: 16966687. DOI: 10.1200/JCO.2006.06.0913
    OpenUrlAbstract/FREE Full Text
    1. Aghajanian C,
    2. Blank SV,
    3. Goff BA,
    4. Judson PL,
    5. Teneriello MG,
    6. Husain A,
    7. Sovak MA,
    8. Yi J and
    9. Nycum LR
    : 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 30(17): 2039-2045, 2012. PMID: 22529265. DOI: 10.1200/JCO.2012.42.0505
    OpenUrlAbstract/FREE Full Text
    1. Coleman RL,
    2. Brady MF,
    3. Herzog TJ,
    4. Sabbatini P,
    5. Armstrong DK,
    6. Walker JL,
    7. Kim BG,
    8. Fujiwara K,
    9. Tewari KS,
    10. O’Malley DM,
    11. Davidson SA,
    12. Rubin SC,
    13. DiSilvestro P,
    14. Basen-Engquist K,
    15. Huang H,
    16. Chan JK,
    17. Spirtos NM,
    18. Ashfaq R and
    19. Mannel RS
    : Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 18(6): 779-791, 2017. PMID: 28438473. DOI: 10.1016/S1470-2045(17)30279-6
    OpenUrlCrossRefPubMed
  16. ↵
    1. Colombo N,
    2. Sessa C,
    3. du Bois A,
    4. Ledermann J,
    5. McCluggage WG,
    6. McNeish I,
    7. Morice P,
    8. Pignata S,
    9. Ray-Coquard I,
    10. Vergote I,
    11. Baert T,
    12. Belaroussi I,
    13. Dashora A,
    14. Olbrecht S,
    15. Planchamp F,
    16. Querleu D and ESMO-ESGO Ovarian Cancer Consensus Conference Working Group
    : ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease†. Ann Oncol 30(5): 672-705, 2019. PMID: 31046081. DOI: 10.1093/annonc/mdz062
    OpenUrlCrossRefPubMed
  17. ↵
    1. Romeo M,
    2. Pardo JC,
    3. Martínez-Cardús A,
    4. Martínez-Balibrea E,
    5. Quiroga V,
    6. Martínez-Román S,
    7. Solé F,
    8. Margelí M and
    9. Mesía R
    : Translational research opportunities regarding homologous recombination in ovarian cancer. Int J Mol Sci 19(10): 3249, 2018. PMID: 30347758. DOI: 10.3390/ijms19103249
    OpenUrlCrossRefPubMed
    1. Lord CJ and
    2. Ashworth A
    : Mechanisms of resistance to therapies targeting BRCA-mutant cancers. Nat Med 19(11): 1381-1388, 2013. PMID: 24202391. DOI: 10.1038/nm.3369
    OpenUrlCrossRefPubMed
    1. Kim Y,
    2. Kim A,
    3. Sharip A,
    4. Sharip A,
    5. Jiang J,
    6. Yang Q and
    7. Xie Y
    : Reverse the resistance to PARP inhibitors. Int J Biol Sci 13(2): 198-208, 2017. PMID: 28255272. DOI: 10.7150/ijbs.17240
    OpenUrlCrossRefPubMed
    1. D’Andrea AD
    : Mechanisms of PARP inhibitor sensitivity and resistance. DNA Repair (Amst) 71: 172-176, 2018. PMID: 30177437. DOI: 10.1016/j.dnarep.2018.08.021
    OpenUrlCrossRefPubMed
    1. Liu L,
    2. Cai S,
    3. Han C,
    4. Banerjee A,
    5. Wu D,
    6. Cui T,
    7. Xie G,
    8. Zhang J,
    9. Zhang X,
    10. McLaughlin E,
    11. Yin M,
    12. Backes FJ,
    13. Chakravarti A,
    14. Zheng Y and
    15. Wang QE
    : ALDH1A1 contributes to PARP inhibitor resistance via enhancing DNA repair in BRCA2–/– ovarian cancer cells. Mol Cancer Ther 19(1): 199-210, 2020. PMID: 31534014. DOI: 10.1158/1535-7163.MCT-19-0242
    OpenUrlAbstract/FREE Full Text
    1. Kim DS,
    2. Camacho CV and
    3. Kraus WL
    : Alternate therapeutic pathways for PARP inhibitors and potential mechanisms of resistance. Exp Mol Med 53(1): 42-51, 2021. PMID: 33487630. DOI: 10.1038/s12276-021-00557-3
    OpenUrlCrossRefPubMed
  23. ↵
    1. Norquist B,
    2. Wurz KA,
    3. Pennil CC,
    4. Garcia R,
    5. Gross J,
    6. Sakai W,
    7. Karlan BY,
    8. Taniguchi T and
    9. Swisher EM
    : Secondary somatic mutations restoring BRCA1/2 predict chemotherapy resistance in hereditary ovarian carcinomas. J Clin Oncol 29(22): 3008-3015, 2011. PMID: 21709188. DOI: 10.1200/JCO.2010.34.2980
    OpenUrlAbstract/FREE Full Text
    1. Kondrashova O,
    2. Nguyen M,
    3. Shield-Artin K,
    4. Tinker AV,
    5. Teng NNH,
    6. Harrell MI,
    7. Kuiper MJ,
    8. Ho GY,
    9. Barker H,
    10. Jasin M,
    11. Prakash R,
    12. Kass EM,
    13. Sullivan MR,
    14. Brunette GJ,
    15. Bernstein KA,
    16. Coleman RL,
    17. Floquet A,
    18. Friedlander M,
    19. Kichenadasse G,
    20. O’Malley DM,
    21. Oza A,
    22. Sun J,
    23. Robillard L,
    24. Maloney L,
    25. Bowtell D,
    26. Giordano H,
    27. Wakefield MJ,
    28. Kaufmann SH,
    29. Simmons AD,
    30. Harding TC,
    31. Raponi M,
    32. McNeish IA,
    33. Swisher EM,
    34. Lin KK,
    35. Scott CL and AOCS Study Group
    : Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma. Cancer Discov 7(9): 984-998, 2017. PMID: 28588062. DOI: 10.1158/2159-8290.CD-17-0419
    OpenUrlAbstract/FREE Full Text
  25. ↵
    1. Lin KK,
    2. Harrell MI,
    3. Oza AM,
    4. Oaknin A,
    5. Ray-Coquard I,
    6. Tinker AV,
    7. Helman E,
    8. Radke MR,
    9. Say C,
    10. Vo LT,
    11. Mann E,
    12. Isaacson JD,
    13. Maloney L,
    14. O’Malley DM,
    15. Chambers SK,
    16. Kaufmann SH,
    17. Scott CL,
    18. Konecny GE,
    19. Coleman RL,
    20. Sun JX,
    21. Giordano H,
    22. Brenton JD,
    23. Harding TC,
    24. McNeish IA and
    25. Swisher EM
    : BRCA reversion mutations in circulating tumor DNA predict primary and acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma. Cancer Discov 9(2): 210-219, 2019. PMID: 30425037. DOI: 10.1158/2159-8290.CD-18-0715
    OpenUrlAbstract/FREE Full Text
    1. Klotz DM and
    2. Wimberger P
    : Overcoming PARP inhibitor resistance in ovarian cancer: what are the most promising strategies? Arch Gynecol Obstet 302(5): 1087-1102, 2020. PMID: 32833070. DOI: 10.1007/s00404-020-05677-1
    OpenUrlCrossRefPubMed
    1. Hinchcliff E,
    2. Chelariu-Raicu A and
    3. Westin SN
    : Current and future landscape of poly (ADP-ribose) polymerase inhibition resistance. Curr Opin Obstet Gynecol 33(1): 19-25, 2021. PMID: 33315700. DOI: 10.1097/GCO.0000000000000678
    OpenUrlCrossRefPubMed
  28. ↵
    1. Gadducci A and
    2. Cosio S
    : The resistance to PARP inhibitors in epithelial ovarian cancer: State of art and perspectives of biological and clinical research. J Transl Sci 7: 1-8, 2021.
    OpenUrl
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Reprints and Permissions
Response to Chemotherapy and Clinical Outcome of Patients With Recurrent Epithelial Ovarian Cancer After PARP Inhibitor Maintenance Treatment: A Multicenter Retrospective Italian Study
ANGIOLO GADDUCCI, STEFANIA COSIO, FABIO LANDONI, ANDREA ALBERTO LISSONI, PAOLO ZOLA, MARIA ELENA LAUDANI, ANTONIO ARDIZZOIA, ANGELA GAMBINO, ENRICO SARTORI
Anticancer Research Apr 2022, 42 (4) 2017-2022; DOI: 10.21873/anticanres.15681
Twitter logo Facebook logo Mendeley logo

Jump to section

Keywords