Ovarian Cancer Research From the 2022 ASCO® Annual Meeting: Treatment, Clinician Engagement, and the Future of Early Detection

The American Society of Clinical Oncology (ASCO®) held its Annual Meeting from June 3 through June 7, 2022, and featured more than 5000 abstracts on new oncology research and live interactive sessions from industry and clinical experts on the latest in oncology technologies and practices.
 
Colleen McCormick, MD, is currently a member of the department of obstetrics and gynecology, and faculty of the gynecologic oncology fellowship program at the University of New Mexico School of Medicine in Albuquerque. Dr McCormick attended The Johns Hopkins School of Medicine, where she also completed an obstetrics and gynecology residency and gynecologic oncology fellowship. She then spent 12 years in private practice in Portland, Oregon, where she built a clinical trials program and was involved in resident education.
 
Dr McCormick shared her perspective on groundbreaking ovarian cancer research presented at the 2022 ASCO Annual Meeting.

What was the single most practice-changing research on ovarian cancer presented at this year’s conference?

The highlight for ovarian cancer at this year’s ASCO Annual Meeting was the ATHENA-MONO trial (ClinicalTrials.gov Identifier: NCT03522246).¹ The ATHENA-MONO trial examined the use of rucaparib, a poly adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitor, for maintenance therapy after first-line treatment of ovarian cancer. Women who had completed first-line treatment consisting of surgery and chemotherapy were then randomly assigned to rucaparib or placebo for maintenance therapy. Women who received rucaparib had a median progression-free survival (PFS) of 20.2 months compared with 9.2 months for those who received placebo. For women with homologous recombination deficiency (HRD), PFS was 28.7 months with rucaparib vs 11.3 months with placebo. In a subgroup analysis, even women with tumors without evidence of HRD showed a benefit. Patients who received rucaparib had a PFS of 12.1 months compared with patients who received placebo, who had a PFS of 9.1 months.

This trial is important as it confirms the beneficial role of PARP inhibitor maintenance therapy after first-line treatment of ovarian cancer. The results are in line with those of the PRIMA trial (ClinicalTrials.gov Identifier: NCT02655016), which was a randomized, double-blind, phase 3 trial in which women with ovarian cancer undergoing maintenance therapy with niraparib — another PARP inhibitor — had significantly greater PFS than those given placebo.² ATHENA-MONO reinforces that maintenance therapy with PARP inhibitors after first-line treatment of ovarian cancer provides clinical benefit to all women. Clinicians should discuss this treatment option with their patients after the completion of upfront treatment.
 
I’m cheating because you asked for just one, but the data presented by Dr Toshiyuki Seki are also important.³ This study looked at historical data comparing survival outcomes for patients with advanced ovarian clear cell carcinoma (ACCC) before bevacizumab was approved for ACCC treatment vs after it was approved for ACCC treatment in Japan. This is a rare, aggressive form of ovarian cancer that is more prevalent in Asian countries; thus, we have less data about the best treatment options for ACCC. This study showed statistically and clinically significant improvement in PFS (29.7 months vs 12.5 months; P =.006) and overall survival (51.4 vs 34.7 months; P =.027).³ For women with this rare form of ovarian cancer, bevacizumab maintenance therapy appears to provide significant benefit. Clinicians should discuss this treatment option with their patients after completion of upfront treatment.

Analysis of tumor-based next-generation sequencing (tbNGS) in a large cohort of patients with high-grade epithelial ovarian cancer revealed that most patients (74.6%) had an actionable mutation, and certain genetic patterns were associated with outcomes such as PFS and overall survival.⁴ What impact does tbNGS have on therapeutic targets and clinical decision tools in patients with ovarian cancer?

As we move to a more molecular-based understanding of cancer, we are able to develop new treatments that target molecular changes. Molecular profiling of tumors allows us to find molecular changes and make treatment decisions based on those changes.⁵ For ovarian cancer, BRCA and HRD status are very important in guiding decisions regarding use and benefit of PARP inhibitors.⁶ Germline testing for BRCA is important for assessing a patient’s risk of developing other cancers and provides information about potential familial risks. If germline testing is negative, somatic testing of the tumor should be done to check for these mutations.⁷ More extensive somatic testing allows for identification of other potential targets and therapies. Additionally, it can help identify mutations that would qualify a patient for a clinical trial, which provides more treatment options for patients and is how we are able to develop new therapies.

Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin improves overall survival in patients with epithelial ovarian cancer; however, cisplatin is associated with significant renal toxicity. A prospective study showed that adding sodium thiosulfate as adjuvant therapy to HIPEC with cisplatin reduced nephrotoxicity.⁸ Is there a need for more therapies that protect renal function in these patients?

The use of HIPEC for ovarian cancer is a promising avenue, and several randomized trials have shown improved outcomes.^9,10 However, further large clinical trials are planned, and the results of these trials are needed before HIPEC becomes the standard of care. The toxicities are certainly one of the stumbling blocks that needs to be overcome before HIPEC can be routinely adopted.¹¹ Upcoming trials will definitely focus on ways to decrease toxicity.

Researchers presented an educational program for gynecologists regarding maintenance therapy for ovarian cancer, as they are more likely than gynecologic oncologists to consistently see patients with ovarian cancer.¹² How much of a problem is continuity of care for patients with ovarian cancer, and do you think an educational program for gynecologists is an effective way to address it?

It is not accurate to say that gynecologists are more likely to see ovarian cancer patients than gynecologic oncologists. Distance from the specialist can indeed be problematic for many patients. Outreach, improved utilization of virtual visits, and shared surveillance with local gynecologists and medical oncologists are certainly important strategies to address these concerns and to ensure that patients have access to care.¹³ However, the role of the gynecologist should not be managing maintenance chemotherapy or targeted therapies for patients with gynecologic cancer.
 
The gynecologist should be aware of signs and symptoms that would be concerning in a patient with ovarian cancer. Additionally, gynecologists are on the front lines, seeing patients without a diagnosis but with a family history of gynecologic cancers. Educating gynecologists regarding the importance of family history, genetic counseling/testing, and the best management strategies for risk reduction for patients with increased genetic risk for cancer is very important.¹⁴ Improved awareness of, and access to, genetic testing allows for prophylactic surgery, which can prevent cancer.

A common concern with ovarian cancer among patients, clinicians, and researchers is ovarian high-grade serous carcinoma, which is the most lethal form and can go undetected until it is in its late stages. Several early detection tests and biomarkers, such as tumor immune microenvironment,¹⁵ DNA methylation signatures,¹⁶ and others were discussed in abstracts. Are there any you would highlight as promising?

Finding a screening method for ovarian cancer has long been the goal. However, thus far we have come up short. There are several intriguing early scientific studies, but at this time they all remain hypothesis-generating and are not yet ready for clinical use.^17,18

References

1. Monk BJ, Parkinson C, Lim MC, et al. A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45).  J Clin Oncol. Published online June 6, 2022. doi:10.1200/JCO.22.01003
 
2. González-Martín A, Pothuri B, Vergote I, et al; for the PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962
 
3. Seki T, Tate S, Nishikimi K, et al. Bevacizumab in first-line chemotherapy to improve the survival outcome for advanced ovarian clear cell carcinoma: a multicenter, retrospective analysis. J Clin Oncol. Published online June 2, 2022. doi:10.1200/JCO.2022.40.16_suppl.5502
 
4. Foster K, Shaw KR, Jin J, et al. Clinical implications of tumor-based next-generation sequencing in ovarian cancer. J Clin Oncol. Published online June 2, 2022. doi:10.1200/JCO.2022.40.16_suppl.5545
 
5. Malone ER, Oliva M, Sabatini PJB, Stockley TL, Siu LL. Molecular profiling for precision cancer therapies. Genome Med. 2020;12(1):8. doi:10.1186/s13073-019-0703-1
 
6. Ngoi NYL, Tan DSP. The role of homologous recombination deficiency testing in ovarian cancer and its clinical implications: do we need it? ESMO Open. 2021;6(3):100144. doi:10.1016/j.esmoop.2021.100144
 
7. Konstantinopoulos PA, Norquist B, Lacchetti C, et al. Germline and somatic tumor testing in epithelial ovarian cancer: ASCO guideline. J Clin Oncol. 2020;38(11):1222-1245. doi:10.1200/JCO.19.02960
 
8. Santiago NL, Han ES, Raoof M, et al. Cisplatin-induced nephrotoxicity in hyperthermic intraperitoneal chemotherapy (HIPEC) is mitigated by sodium thiosulfate: clinical and toxicotranscriptomic results of a prospective trial. J Clin Oncol. Published online June 2, 2022. doi:10.1200/JCO.2022.40.16_suppl.5570
 
9. Lim MC, Chang S-J, Park B, et al; for the HIPEC for Ovarian Cancer Collaborators. Survival after hyperthermic intraperitoneal chemotherapy and primary or interval cytoreductive surgery in ovarian cancer: a randomized clinical trial. JAMA Surg. 2022;157(5):374-383. doi:10.1001/jamasurg.2022.0143
 
10. van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med. 2018;378(3):230-240. doi:10.1056/NEJMoa1708618
 
11. Chen W-C, Huang H-J, Yang L-Y, et al. Hyperthermic intraperitoneal chemotherapy for recurrent epithelial ovarian cancer. Biomed J. Published online October 14, 2021. doi:10.1016/j.bj.2021.10.003
 
12. Carranza V, Taylor BC, Gitzinger SH, Fowler JB, Hall J. The impact of virtual live education on the competence and knowledge of gynecologists caring for ovarian cancer patients. J Clin Oncol. Published online June 2, 2022. doi:10.1200/JCO.2022.40.16_suppl.e23003
 
13. Temkin SM, Smeltzer MP, Dawkins MD, et al. Improving the quality of care for patients with advanced epithelial ovarian cancer: program components, implementation barriers, and recommendations. Cancer. 2022;128(4):654-664. doi:10.1002/cncr.34023
 
14. Committee Opinion No. 716: The role of the obstetrician-gynecologist in the early detection of epithelial ovarian cancer in women at average risk. Obstet Gynecol. 2017;130(3):e146-e149. doi:10.1097/AOG.0000000000002299
 
15. Zhu L, Cao G, Hua D, Cui L, Zhao X, Wang S. The tumor immune microenvironment correlates with neoadjuvant chemotherapy response in high-grade serious ovarian cancer. J Clin Oncol. Published online June 2, 2022. doi:10.1200/JCO.2022.40.16_suppl.e17605
 
16. Ferris JS, Wang T, Wang S, et al. Identifying DNA methylation signatures in high-grade serous ovarian cancer: results vary by control tissue type. J Clin Oncol. Published online June 2, 2022. doi:10.1200/JCO.2022.40.16_suppl.e17559
 
17. Otsuka I, Matsuura T. Screening and prevention for high-grade serous carcinoma of the ovary based on carcinogenesis — fallopian tube- and ovarian-derived tumors and incessant retrograde bleeding. Diagnostics (Basel). 2020;10(2):120. doi:10.3390/diagnostics10020120
 
18. Han C, Bellone S, Siegel ER, et al. A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma. Gynecol Oncol. 2018;149(3):585-591. doi:10.1016/j.ygyno.2018.03.050