Explore Ovarian Cancer Treatments Through Clinical Trials

The National Institutes of Health (NIH) estimates that ovarian cancer (OC) will have accounted for 1.2% of new cases and 2.3% of all cancer deaths in the United States in 2020.¹

The most recent global statistics from 2018 show that OC is ranked eighth in cancer incidence rates for women, with more than 295,000 or 3.8% cases diagnosed in 2018.²

There are no routine screenings for OC, which often results in delayed diagnosis beyond stage I and II, secondary to generalized vague symptoms.³ About 70% of the cases are diagnosed as advanced stage III or IV OC.¹ The patients' 5-year survival rate varies greatly, depending on the stage at which they are initially diagnosed (FIGURE³). The CDC reported that new cases are 10.2 of 100,000, with 6.6 of 100,000 women succumbing to death annually.²

Ovarian Cancer 5-year Relative Survival vs Diagnosis By Stage

EPIDEMIOLOGY

Patients in developed countries have a higher rate of OC, with a peak incidence occurring between 55 and 64 years of age with a higher prevalence in Caucasian women.⁴ The most common type of OC is epithelial, which accounts for about 90% of all cases, and the remaining 10% are considered to be nonepithelial.⁵ About 20% of all OCs have been associated with an inherited gene mutation, eg, BRCA1, BRCA2, MLH1, MSH2. This malignancy has been linked to 1 of 3 hereditary patterns: ovarian cancer alone, ovarian cancer plus breast cancer, and ovarian cancer plus colon cancer.⁶ Women of Ashkenazi Jewish and Eastern European descent are more likely to be carriers of BRCA gene mutations and therefore are at an increased risk of developing OC.⁷

DIAGNOSIS AND STAGING

The National Comprehensive Cancer Network (NCCN) does not offer screening recommendations for ovarian cancer. Online table 1⁷ outlines common symptoms that might be produced by OC. If a patient is experiencing any of these signs or symptoms for greater than 2 weeks, diagnostic tests such as a CA-125 blood test, transvaginal ultrasound, or vaginal pelvic exam may be ordered to investigate the presence of OC.⁸ The staging of OC is determined postsurgically, which should be performed by a gynecologic oncologist and then examined microscopically by a pathologist.⁷

Common symptoms

TREATMENT

Treatment options for OC include chemotherapy, hormone therapy, immunotherapy, radiation, surgery, and targeted therapy (Table 2^9-13).⁹ The NCCN Clinical Practice Guidelines for OC recommend that the primary treatment consist of debulking surgery, plus systemic chemotherapy in most patients.¹⁰

Common ovarian cancer treatments

Clinicians use genetic testing to assess for specific gene mutations, such as BRCA, homologous-recombination deficiency, which will guide treatment decisions.¹⁰ This allows clinicians to prescribe a targeted therapy that includes poly-ADP ribose polymerase (PARP) inhibitors and/or vascular endothelial growth factor inhibitors.¹⁰

Systemic immunotherapy enhances the activity of the immune system. Immune checkpoint inhibitors target key surface markers, eg, cytotoxic T-lymphocyte-associated protein 4, programmed cell death ligand, and programmed cell death protein 1.¹¹

Hormone therapy involves the use of hormones or hormone-blocking agents acting as anti-estrogen agents to suppress OC tumor growth. This type of therapy involves 3 classes of drugs: aromatase inhibitors, luteinizing-hormone-releasing hormone agonists, and tamoxifen. This mode of systemic therapy is rarely employed in epithelial OC but is more commonly used in refractory ovarian stromal tumors.

ON THE HORIZON

PARP inhibitors are vital in the treatment and maintenance of OC and may improve outcomes. Some recent clinical trials, ie, PAOLA-1/ENGOT-OV26, PRIMA/ENGOT-OV26, and SOLO-1, (Online table 3^14-18) show success in patients with OC.¹⁹

PARP inhibitors for ovarian cancer

Clinical trials evaluating combination products, eg, cediranib and olaparib, in patients that are considered to platinum-resistant and -sensitive, are showing promise. Cediranib, a VEGF inhibitor with olaparib, a PARP inhibitor, restricts blood supply to the area promoting apoptosis of the cancerous cells. Preliminary reports from the ICON 9 study demonstrate a significant improvement in progression-free survival.²⁰

CONCLUSION

OC negatively affects the lives of many women. It continues to remain one of the most lethal malignancies, despite continuing efforts and constant advances in treatments. The poor clinical outcomes associated with OC are attributable to chemotherapy resistance, its increased heterogeneity, and the ineffective tools for detecting the disease early in its course. New treatments are needed to enhance cure rates and provide long-term disease stability against platinum-resistance OC. Cellular and immune therapies combined with genetic testing and precision assays (biomarkers) are promising strategies that will inevitably lead to more favorable clinical outcomes. Accelerated research and novel approaches will also invariably spawn better therapeutic options to extend the life expectancy and improve the health of patients with OC.²¹

REFERENCE

1. United States cancer statistics data visualizations. Centers for Disease Control and Prevention. June 2020. Accessed March 7, 2021. https://www.cdc.gov/cancer/dataviz

2. Worldwide cancer data. World Cancer Research/American Institute for Cancer Research. Accessed February 14, 2021. https://www.wcrf.org/dietandcancer/cancer-trends/worldwide-cancer-data

3. Stages of ovarian cancer. Ovarian Cancer Research Alliance. Accessed February 14, 2021. https://ocrahope.org/patients/about-ovarian-cancer/staging/

4. Gaona-Luviano P, Medina-Gaona LA, Magana-Perez K. Epidemiology of ovarian cancer. Chin Clin Oncol. 2020;9(4):47. doi:10.21037/cco-20-34

5. Ovarian germ cell tumors treatment (PDQ)-health professional version. National Cancer Institute. Updated September 3, 2020. Accessed February 14, 2021. https://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq

6. Risk factors. Ovarian Cancer Research Alliance. Accessed February 14, 2021. https://ocrahope.org/patients/about-ovarian-cancer/risk-factors/

7. Ovarian germ cell tumors treatment (PDQ)-patient version. National Cancer Institute. Updated January 8, 2021. Accessed February 14, 2021. https://www.cancer.gov/types/ovarian/patient/ovarian-epithelial-treatment-pdq

8. About ovarian cancer. Ovarian Cancer Research Alliance. Accessed February 14, 2021. https://ocrahope.org/patients/about-ovarian-cancer/

9. Treatment. Ovarian Cancer Research Alliance. Accessed February 14, 2021. https://ocrahope.org/patients/about-ovarian-cancer/treatment/

10. Kaplan DA. Overview of the updated NCCN guidelines on ovarian cancer. Journal of Clinical Pathways. June 17, 2020. Accessed February 14, 2021. https://www.journalofclinicalpathways.com/overview-updated-nccn-guidelines-ovarian-cancer

11. Borella F, Ghisoni E, Giannone G, et al. Immune checkpoint inhibitors in epithelial ovarian cancer: an overview on efficacy and future perspectives. Diagnostics (Basel). 2020;10(3):146. doi:10.3390/diagnostics10030146

12. Gershenson DM, Bodurka DC, Coleman RL, Lu KH, Malpica A, Sun CC. Hormonal maintenance therapy for women with low-grade serous cancer of the ovary or peritoneum. J Clin Oncol. 2017;35(10):1103-1111. doi:10.1200/JCO.2016.71.0632

13. Shylasree TS, Richa B, Lavanya G, Gulia S. Molecular signatures of gynecological cancers: clinicians perspective. Indian J Surg Oncol. 2021. doi:10.1007/s13193-020-01271-8

14. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379(26):2495-2505. doi:10.1056/NEJMoa1810858

15. Gonazlez-Martin A, Pothuri B, Vergote I, et al. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962

16. Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381(25):2416-2428. doi:10.1056/NEJMoa1911361

17. Coleman RL, Fleming GF, Brady MF, et al. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med. 2019;381(25):2403-2415. doi:10.1056/NEJMoa1909707

18. Clovis Oncology announces completion of target enrollment in the ATHENA trial, a phase 3 maintenance treatment study in front-line, newly-diagnosed advanced ovarian cancer. News release. Clovis Oncology. June 10, 2020. Accessed February 10, 2021. https://ir.clovisoncology.com/investors-and-news/news-releases/press-release-details/2020/Clovis-Oncology-Announces-Completion-of-Target-Enrollment-in-the-ATHENA-Trial-a-Phase-3-Maintenance-Treatment-Study-in-Front-line-Newly-Diagnosed-Advanced-Ovarian-Cancer/default.aspx

19. Mirza MR, Coleman RL, Gonzalez-Martin A, et al. The forefront of ovarian cancer therapy: update on PARP inhibitors. Ann Oncol. 2020;31(9):1148-1159. doi:10.1016/j.annonc.2020.06.004

20. Liu JF, Barry WT, Birrer M, et al. Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer. Ann Oncol. 2019;30(4):551-557. doi:10.1093/annonc/mdz018

21. Chandra A, Pius C, Nabeel M, et al. Ovarian cancer: current status and strategies for improving therapeutic outcomes. Cancer Med. 2019;8(16):7018-7031. doi:10.1002/cam4.2560