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Pembrolizumab in combination with bevacizumab and oral cyclophosphamide in heavily pre-treated platinum-resistant ovarian cancer
  1. Angeliki Andrikopoulou1,
  2. Michalis Liontos1,
  3. Efthymia Skafida1,
  4. Konstantinos Koutsoukos1,
  5. Kleoniki Apostolidou1,
  6. Maria Kaparelou1,
  7. Angeliki Rouvalis1,
  8. Garyfallia Bletsa2,
  9. Meletios-Athanasios Dimopoulos1 and
  10. Flora Zagouri1
  1. 1Oncology Unit, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
  2. 2Hellenic Anticancer Institute, 10680 Athens, Greece, Attica, Greece
  1. Correspondence to Dr Angeliki Andrikopoulou, Oncology Unit, Dept of Clinical Therapeutics, National and Kapodistrian University of Athens, 11528 Athens, Greece; aggelikiandrikop{at}gmail.com

Abstract

Objective Immune checkpoint inhibitors have been widely implemented in the treatment of solid tumors. Combinations of immune checkpoint inhibitors with chemotherapy, anti-vascular endothelial growth factor (VEGF) compounds, and poly-adenosine diphosphate-ribose polymerase inhibitors (PARP) are under evaluation in ovarian cancer. We aim to explore the efficacy of pembrolizumab in combination with bevacizumab and oral cyclophosphamide in patients with recurrent epithelial ovarian cancer.

Methods This was a retrospective study of all patients who received pembrolizumab in combination with bevacizumab and oral cyclophosphamide for recurrent platinum-resistant heavily pre-treated ovarian cancer in the Oncology Unit of Alexandra University Hospital from January 2021 to July 2022.

Results Median age at diagnosis was 56 years (SD 9.2; range 37–72). All patients were diagnosed with high-grade serous ovarian carcinoma. Initial disease stage was International Federation of Gynecology and Obstetrics (FIGO) IIIC in most cases (11/15, 73%). Patients were heavily pre-treated with a median of six (range 4–9) prior lines of systemic therapy. All patients experienced disease progression on first-line platinum-based chemotherapy, and median progression-free survival on first-line treatment was 22 months (95% CI 10.6 to 33.4). Patients received a median of four cycles of pembrolizumab in combination with cyclophosphamide and bevacizumab (range 3–20). Overall response rate was 13% (2/15) and disease control rate was 33% (5/15) with two patients achieving partial response and three patients achieving stable disease. Median progression-free survival was 3.5 months (95% CI 1.3 to 5.7) and the 6-month progression-free survival rate was 20%. Treatment was well tolerated with no dose-limiting toxicities.

Conclusion We showed that the combination of pembrolizumab with bevacizumab and oral cyclophosphamide is an effective alternative in heavily pre-treated patients with ovarian cancer who have otherwise limited treatment options.

  • Ovarian Neoplasms

Data availability statement

Data presented in our study can be found in the patients’ archives which are safely stored by our institution. The datasets generated during the current study are available from the corresponding author upon request.

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Data availability statement

Data presented in our study can be found in the patients’ archives which are safely stored by our institution. The datasets generated during the current study are available from the corresponding author upon request.

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Footnotes

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  • AA and ML contributed equally.

  • Contributors Data curation, AA, ES, AR, MK, and GB; Formal analysis, KA and GB; Investigation, ES, AR, and GB; Project administration, ML and FZ; Supervision, KK, M-AD, and FZ; Writing – original draft, AA and MK; Writing – review & editing, AA, ML, and KK; Guarantor, FZ.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests ML has received honoraria from Roche, Astra Zeneca, Astellas, MSD, Janssen, Bristol-Myers-Squibb, and IPSEN. MAD has received honoraria from participation in advisory boards from Amgen, Bristol-Myers-Squibb, Celgene, Janssen, and Takeda. FZ has received honoraria for lectures and has served in an advisory role for Astra-Zeneca, Daiichi, Eli-Lilly, Merck, Novartis, Pfizer, and Roche. KK has received honoraria from Roche, BMS, MSD, and IPSEN. MAD has received honoraria from participation in advisory boards from Amgen, Bristol-Myers-Squibb, Celgene, Janssen, and Takeda. The remaining authors declare no conflict of interest.

  • Provenance and peer review The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of Alexandra University Hospital.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.