Advances in Ovarian Cancer Care and Unmet Treatment Needs for Patients With Platinum Resistance

Abstract

ImportancePlatinum-based chemotherapy has been the standard of care for ovarian cancer for the past 3 decades. Although most patients respond to platinum-based treatment, emergence of platinum resistance in recurrent ovarian cancer is inevitable during the disease course. Outcomes for patients with platinum-resistant ovarian cancer are poor, and options remain limited, highlighting a substantial unmet need for new treatment options.ObservationsThis review summarizes the current and evolving treatment landscape for platinum-resistant ovarian cancer with a focus on the development of novel compounds. Biologic and targeted therapies such as bevacizumab and poly (ADP-ribose) polymerase (PARP) inhibitors—originally approved in the platinum-resistant setting but since withdrawn—are now used in the up-front or platinum-sensitive setting, prolonging the duration of platinum sensitivity and delaying the use of nonplatinum options.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. In this contemporary setting, recent trials in platinum-resistant ovarian cancer have mostly had negative outcomes, with none having a clinically significant effect on progression-free or overall survival since the approval of bevacizumab in combination with chemotherapy. Nonetheless, a multitude of new therapies are under evaluation; preliminary results are encouraging. A focus on biomarker-directed treatment and patient selection may provide greater success in identifying novel therapies for treating platinum-resistant ovarian cancer.Conclusions and RelevanceAlthough many clinical trials in platinum-resistant ovarian cancer have had 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.

Losartan rewires ovarian cancer tumor-immune microenvironment and suppresses IGF-1 to amplify chemo-immunotherapy sensitivity

“…OvCa has the highest mortality rate of all gynecological cancers. Despite high initial response rates towards chemotherapy, approximately 70% of all patients relapse and develop resistant disease within five years after diagnosis 2 . There is an urgent need for the development of novel and effective therapeutic strategies.…”

“…The density and spatial distribution of immune infiltrates in tumors are associated with patient survival and response to immune therapy in melanoma, pancreatic, and other cancers 2,37-39 . In OvCa, although checkpoint inhibitors have had limited efficacy, a positive trend in objective response rate (ORR) was reported for patients with high CD8 T cells who received avelumab in JAVELIN Ovarian 200 35 or pembrolizumab in KEYNOTE-100 40 .…”

“…Ovarian Cancer (OvCa) is the most lethal gynecologic malignancy worldwide, with an estimated 19,710 new diagnoses and 13,270 deaths in the U.S. in 2023 1 . Following initial debulking surgery, OvCa patients generally receive a chemotherapy regimen that includes a platinum complex (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel) 2 . However, despite initial responsiveness, the majority of patients with advanced OvCa eventually relapse with resistant disease 2 .…”

“…Following initial debulking surgery, OvCa patients generally receive a chemotherapy regimen that includes a platinum complex (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel) 2 . However, despite initial responsiveness, the majority of patients with advanced OvCa eventually relapse with resistant disease 2 . Outcomes for patients with platinum-resistant OvCa are poor, and options remain limited, making the development of new OvCa treatment a high clinical priority.…”

Targeted DNA sequencing of high‐grade serous ovarian carcinoma reveals association of TP53 mutations with platinum resistance when combined with gene expression

“…Approximately 85%–90% of ovarian cancer originates in epithelial cells and is thus designated epithelial ovarian cancer (EOC). High mortality of this malignancy is mainly due to most EOC patients being diagnosed in advanced stages (International Federation of Gynecology and Obstetrics [FIGO] III or IV) when the 5‐year survival rate reaches approximately 20%–45% 2,3 and treatment options are often limited 4 …”