Current Treatments, Future Strategies for Platinum-Resistant Ovarian Cancer: Review

A new review outlined the current treatment landscape for platinum-resistant ovarian cancer and focused on the development of novel compounds. The findings were published in JAMA Oncology.

Although many clinical trials for this disease have yielded negative outcomes, “these failures provide insights into how clinical trial design, biomarker-directed therapy, and patient selection could facilitate future successes in platinum-resistant ovarian cancer treatment,” authors wrote.

For the past 30 years, platinum-based chemotherapy has been the standard of care for ovarian cancer.

Credit: Sherry Young - stock.adobe.com

For the past 30 years, platinum-based chemotherapy has been the standard of care for ovarian cancer, though some patients experience platinum resistance in recurrent forms of the disease. Outcomes for these patients are poor, researchers explained, and treatment options remain limited.

However, biologics and targeted therapies like bevacizumab and poly (ADP-ribose) polymerase (PARP) inhibitors are now used in the platinum-sensitive setting. These agents can prolong the duration of platinum sensitivity and help delay use of nonplatinum options.

“The greater use of maintenance therapy and the emphasis on using platinum beyond first-line treatment has most likely been associated with a greater number of lines of platinum therapy before a patient is designated as having platinum-resistant ovarian cancer,” authors wrote.

In addition, since the approval of bevacizumab plus chemotherapy, no trials in platinum-resistant ovarian cancer have resulted in a clinically significant effect on progression-free survival or overall survival. Bevacizumab was approved in the United States in 2014 after a clinical trial found the treatment plus chemotherapy was associated with an overall response rate of 30.9%.

The treatment has been associated with adverse events, including hypertension, hemorrhage, and thrombosis. Despite the success of bevacizumab, other antiangiogenic therapies, such ascediranib, have failed to improve outcomes or been withdrawn from development.

Similarly, immunotherapies, which have been successful in treating other solid malignant neoplasms, have had less promise in ovarian cancer. Despite this, some biomarker-based strategies in patient subgroups defined by PD-L1 and CD8 expression are being explored.

Preliminary results of new therapies under evaluation are promising, while focusing on biomarker directed treatment and patient selection could aid investigators in identifying novel therapies for treating platinum-resistant ovarian cancer, authors added.

Ovarian cancer is the third most common gynecologic malignant neoplasm around the world, and is the deadliest. In 2022 alone, 12,810 deaths were reported in the United States.

However, the increased uptake of maintenance therapy in platinum-sensitive patients may have contributed to a decline in the annual death rate.

The disease has a response rate of 75% to 80 % with frontline therapy, although around 70% of tumors will recur and become platinum-resistant. While several mechanisms of platinum resistance have been proposed, ultimately the mechanisms are “heterogenous and unclear,” authors wrote.

Potential future therapeutic strategies for platinum-resistant ovarian cancer include antibody drug conjugates, replication stress inhibitors, and other targeted therapies. These include phosphatidylinositol-3-kinase inhibitors, AKT inhibitors, antiglucocorticoids, antiangiogenic therapies, andnewcombinationswithvascular endothelial growth factor inhibitors. 

Future strategies that aim to improve patient selection and personalize treatment will also depend on identifying biomarkers that are differentially expressed on ovarian cancer vs normal tissues, researchers explained.

Overall, new maintenance strategies and the strategy of using platinum therapy until it’s no longer appropriate have resulted in a cohort of heavily pretreated patients with platinum-resistant ovarian cancer.

“The effects of heavier pretreatment on disease biology demand more thoughtful implementation and design of clinical trials,” authors concluded. “Ultimately, effective treatment must provide clinically meaningful improvements in [progression-free survival] without compromising [quality of life].”

Reference

Richardson DL, Eskander RN, and O’Malley DM. Advances in ovarian cancer care and unmet treatment needs for patients with platinum resistance a narrative review. JAMA Oncol. Published online April 20, 2023. doi: 10.1001/jamaoncol.2023.0197