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Bevacizumab treatment for patients with recurrent ovarian cancer

Updated: Sep 10


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Ovarian cancer is highly prevalent and accounts for high mortality rate among cancers relating to female reproductive system (1). As per the Global Cancer Statistics (2020), every year almost 24,000 women are diagnosed with ovarian cancer. Most of the patients are diagnosed at advanced stages. Unfortunately, it is noted that 70% of patients treated with standard Platinum chemotherapy have recurrence of ovarian cancer within 18 to 28 months (1, 2).


Challenges with recurrent ovarian cancer


Recurrent ovarian cancer has been a major concern. First line treatment options include Platinum based chemotherapy drugs such as carboplatin and cisplatin (3). Recurrence of ovarian cancer within 6 month treatment period is quite common, leading to Platinum resistant ovarian cancer. Around 25% of ovarian cancer patients are prone to Platinum resistance (3).


Treatment options for recurrent ovarian cancer


Treatment options for Platinum resistant ovarian cancer include monotherapy agents such as and Topotecan, pegylated liposomal Doxorubicin (PLD), and Paclitaxel. There have been many instances where combination of two or more chemotherapy agents leads to increased toxicity and decreased efficiency of drug activity. Therefore, recovery prospects for recurrent ovarian cancer patients are quite poor with a median overall survival (OS) rate of 12 months approximately. Hence, there is a dire need to identify novel treatment options that are safer in this population (3).


Earlier treatment options for ovarian cancer include cytoreductive surgery along with Platinum based chemotherapy. This treatment demonstrated good response rate among patients initially, but later resulted in relapse of ovarian cancer within 6 months (4). Combination of monotherapy with biological therapy such as monoclonal antibodies is a promising novel approach. 


Role of Bevacizumab


Vascular Endothelial Growth factor (VEGF) is known to promote angiogenesis resulting in progression of ovarian cancer. Bevacizumab, a monoclonal antibody that targets vascular endothelial growth factor (VEGF) is a preferred treatment option in combination other chemotherapy agents and also as monotherapy for Platinum resistant ovarian cancer (3).


Clinical evidence - Aurelia study


Aurelia study was a phase III open label randomized trail conducted among 361 patients relapsed with ovarian cancer within 6 month time period, after completion of Platinum based therapy(3). Patients were randomly treated with monotherapy or in combination with Bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks). Addition of Bevacizumab to chemotherapy significantly improved PFS and ORR with no new safety signals. Median progression free survival (mPFS) was 6.7 months with Bevacizumab plus chemotherapy and 3.4 months with chemotherapy alone (3). Objective Response Rate (ORR) was 30.9% with Bevacizumab plus chemotherapy and 12.6% with chemotherapy (3).


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Clinical evidence - OCEANS study


OCEANS study was a randomized, placebo-controlled, blinded, phase III trial conducted among 484 patients with Platinum-sensitive recurrent ovarian cancer (5).

Patients were randomly treated with Gemcitabine plus Bevacizumab or Placebo for 6 to 10 cycles. There was a statistically significant improvement in PFS and ORR in GC plus BVZ followed by BVZ until progression as compared to GC plus PL in platinum-sensitive ROC (See Figure 1). mPFS was 12.4 months with Gemcitabine plus Bevacizumab and 8.4 months in Gemcitabine + Placebo. Objective Response Rate (ORR) was 78.5% with Gemcitabine plus Bevacizumab and 57.4% in Gemcitabine plus Placebo (5).


Figure 1:  Improvement in PFS and ORR in GC plus BVZ  followed by BVZ until progression as compared to GC plus PL in platinum-sensitive ROC.

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In Platinum sensitive recurrent ovarian cancer, a significant improvement in mPFS and ORR was noted in Gemcitabine plus Bevacizumab treatment combination, followed by Bevacizumab until progression, in comparison to Gemcitabine plus Placebo (5).


Clinical evidence - GOG-0218 trial 


GOG-0218 trial was conducted to evaluate the efficacy of Bevacizumab in high grade ovarian cancer patients (6). 1,873 patients were randomly treated with Carboplatin-paclitaxel +/- concurrent Bevacizumab/Placebo and patient KELIM values were estimated during the first 100 chemotherapy days (6). 


mPFS of 9.1 months was noted in Bevacizumab and 5.6 months in Placebo. mOS of 35.1 months was noted in Bevacizumab and 29.1 months in Placebo, with a difference of 6 months.  Patients with unfavourable KELIM score with high-risk diseases (stage  IV, or incompletely resected stage III) were benefited the most from  Bevacizumab therapy (See figure 2) (6). 


Figure 2:   Bevacizumab is effective in patients with  high-risk diseases and poor chemosensitivity - GOG - 0218 validation study.

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Over all, Bevacizumab was effective in patients with high grade ovarian cancer and poor chemosensitivity patients(6).


About the Author


Dr. Sishir Kumar is a medical communications professional with a research doctorate (PhD) in oncology research and drug discovery. He has published 13 articles in reputed international journals like Drug Discovery Today, Nanomedicine, Medicinal Research Reviews, Wiley - Food Bioengineering, Frontiers in Nutrition, etc. His interest and expertise are in publication writing and the development of medico-marketing materials in different therapeutic areas such as Cardiology, Oncology, and Diabetes, etc., He is passionate and keen on the development of effective medical communication materials for a wide variety of clinical research projects. 


Reference


  1. Satora M, Kułak K, Zaremba B, Grunwald A, Świechowska-Starek P, Tarkowski R. New hopes and promises in the treatment of ovarian cancer focusing on targeted treatment—a narrative review. Frontiers in Pharmacology. 2024;15.

  2. Fan Z, Han D, Fan X, Zhao L. Ovarian cancer treatment and natural killer cell-based immunotherapy. Frontiers in Immunology. 2023;14.

  3. Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, et al. Bevacizumab Combined With Chemotherapy for Platinum-Resistant Recurrent Ovarian Cancer: The AURELIA Open-Label Randomized Phase III Trial. Journal of Clinical Oncology. 2014;32(13):1302-8.

  4. Abodunrin F, Tauseef A, Silberstein PT. Bevacizumab combined with platinum-based chemotherapy in patients with primary or relapsed ovarian cancer: Meta-analysis and literature review. Journal of Clinical Oncology. 2022;40(16_suppl):5582-.

  5. Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, 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. Journal of Clinical Oncology. 2012;30(17):2039-45.

  6. You B, Purdy C, Copeland LJ, Swisher EM, Bookman MA, Fleming G, et al. Identification of Patients With Ovarian Cancer Experiencing the Highest Benefit From Bevacizumab in the First-Line Setting on the Basis of Their Tumor-Intrinsic Chemosensitivity (KELIM): The GOG-0218 Validation Study. Journal of Clinical Oncology. 2022;40(34):3965-74.


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