New drugs for ovarian cancer obtain reimbursement

Lynparza passed the Pharmaceutical Reimbursement Evaluation Committee (PREC) of the Health Insurance Review and Assessment Service (HIRA) …improved patient access to first-line maintenance therapy expected

Expanded treatment options for platinum-resistant ovarian cancer, including ADC and immunotherapy

The treatment landscape for ovarian cancer is rapidly changing, including early maintenance therapy to the post-recurrence, platinum-resistant stage.

Given that expanded reimbursement for PARP inhibitors is possible, antibody-drug conjugates (ADCs) and immunotherapies have demonstrated survival benefit in platinum-resistant ovarian cancer, further shaping patient-specific, biomarker-driven treatment strategies.

PARP inhibitor 'Lynparza'

​According to industry sources on July 16, the Pharmaceutical Reimbursement Evaluation Committee (PREC) of the Health Insurance Review and Assessment Service (HIRA) recently recognized the reimbursement appropriateness of 'Lynparza (olaparib)' as a first-line maintenance therapy for homologous recombination deficiency (HRD)-positive advanced ovarian cancer.

​Specifically, Lynparza passed the PREC review as a maintenance therapy in combination with bevacizumab for adult patients with HRD-positive, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who have responded to first-line platinum-based chemotherapy combined with bevacizumab.

This decision opens the possibility of expanding Lynparza's reimbursement, previously centered on BRCA-mutated patients, to include HRD-positive patients. Furthermore, in platinum-resistant ovarian cancer, the folate receptor alpha (FRα)-targeted ADC 'Elahere (mirvetuximab soravtansine)' is undergoing the reimbursement process. At the same time, the immunotherapy 'Keytruda (pembrolizumab)' recently added a new indication, expanding treatment options across the entire spectrum of ovarian cancer.

​A significant majority of ovarian cancer cases are diagnosed at an advanced stage. Even if patients respond to surgery and platinum-based chemotherapy, approximately 70% to 80% experience recurrence. A key characteristic of the disease is that as recurrences repeat, resistance to platinum-based chemotherapies develops, making treatment increasingly difficult.

This PREC decision is significant in that it opens the possibility of broadening the patient population eligible for early maintenance therapy in ovarian cancer.

Recently, the importance of early maintenance therapy, considering not only progression-free survival (PFS) to delay recurrence but also overall survival (OS), has been increasing in ovarian cancer treatment.

​Lynparza demonstrated long-term survival in BRCA-mutant patients in the SOLO-1 study and in HRD-positive patients in the PAOLA-1 study. Notably, the long-term follow-up results of PAOLA-1 supported the clinical value of early maintenance therapy, showing that the combination of Lynparza and bevacizumab reduced the risk of death by 38% in HRD-positive patients.

​Another PARP inhibitor, 'Zejula (niraparib)', is also reimbursed under national health insurance for first-line ovarian cancer maintenance therapy. The industry expects therapeutic strategies for selecting maintenance therapies to be further strengthened by comprehensively considering BRCA mutations, HRD status, and prior therapies.

Platinum-resistant ovarian cancer, The era of ADC therapy

ADC anticancer drug 'Elahere'

​The treatment landscape for platinum-resistant ovarian cancer is also changing.

​Previously, non-platinum chemotherapies such as pegylated liposomal doxorubicin, topotecan, and paclitaxel were primarily used.

However, their treatment response rates and survival benefits were limited, making this a therapeutic area with highly unmet medical needs, with some studies reporting objective response rates (ORRs) in the single digits.

In this situation, Elahere, which secured domestic approval last December, presented a new treatment option as the first folate receptor alpha (FRα)-targeted ADC for ovarian cancer. Its national health insurance reimbursement process also began in earnest after passing the Cancer Disease Review Committee (CDRC) this past May.

Elahere operates by selectively binding to FRα on the surface of cancer cells and then releasing a cytotoxic payload inside the cell. Approximately 35% to 40% of ovarian cancer patients are known to be FRα-positive, meeting the treatment criteria, and its expression is reported to remain relatively consistent from the time of diagnosis through the recurrence stage.

​In the MIRASOL study, Elahere extended the median OS to 16.46 months compared with conventional chemotherapy, approximately 4 months longer than the control group (12.75 months).

It also achieved an ORR of 42.3%, demonstrating a rare, statistically significant improvement in OS in the platinum-resistant ovarian cancer setting.

​Keytruda joins the race…expanding the role of immunotherapy

Immunotherapy 'Keytruda'

​​Immunotherapy has also entered the treatment arena for platinum-resistant ovarian cancer.

Keytruda recently added a therapeutic indication for patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer whose tumors express PD-L1 (CPS 1 or higher) and who have received 1 to 2 prior lines of systemic therapy.

​In the KEYNOTE-B96 study that served as the basis for approval, the Keytruda combination therapy reduced the risk of disease progression or death by 28% and the risk of death by 24%, confirming statistically significant improvements in both PFS and OS. The median OS for the Keytruda group was 18.2 months.

​While conventional immunotherapies previously failed to demonstrate meaningful survival improvements in ovarian cancer, KEYNOTE-B96 study is considered highly significant because it demonstrated clinical efficacy by specifically selecting PD-L1-positive patients.

Previously, ovarian cancer treatment was primarily limited to surgery and platinum-based chemotherapy, and targeted therapy was limited to choosing a PARP inhibitor based on BRCA mutation status.

Recently, the paradigm is rapidly transitioning toward biomarker-driven therapeutic strategies, such as expanding maintenance therapy eligibility based on HRD status and selecting ADCs or immunotherapies based on FRα or PD-L1 expression post-recurrence.

Opinions are also emerging that the importance of companion diagnostics (CDx) will grow alongside therapeutics. The prevailing outlook is that identifying key biomarkers, such as BRCA, HRD, FRα, and PD-L1, at the initial stage of diagnosis to inform the design of patient-specific treatment sequences will become the new standard of care.