PARP anticancer drugs raise expectations of ovarian cancer

[Interview] Lee Taek-sang, professor of obstetrics and gynecology at Boramae Hospital in Seoul

Zejula·Lynparza improve treatment prognosis by applying primary maintenance benefits

BRCA - group has not yet been recognized for its benefit adequacy

Challenges of improving the diagnostic environment

Lee Taek-sang, professor of obstetrics and gynecology at Boramae Hospital, Seoul Metropolitan Government

As benefits are applied to the primary maintenance therapy of PARP inhibitors in ovarian cancer treatment in Korea, the treatment site is rapidly changing.

 

Above all, a specialist evaluates that the use of PARP inhibitors for early treatment has significantly improved the patient's prognosis.

 

However, the expansion of benefits and commercialization of HRd diagnosis in BRCA negative patients are considered tasks to be improved.

 

◆ Improved prognosis with recurrent ovarian cancer and PARP inhibitors Unlike other solid cancers, ovarian cancer has less remote metastasis and excellent sensitivity to anticancer drugs.

 

Therefore, regardless of the stage of ovarian cancer, surgery and chemotherapy are considered the first-line treatment.

 

However, the initial symptoms were insignificant, so cancer was often diagnosed after progression, and eight out of 10 patients suffered recurrence after the first treatment, making treatment difficult.

 

PARP inhibitors have made new changes in the treatment of ovarian cancer.

 

In the past, in addition to cytotoxic anticancer drugs, vascular endothelial growth factor (VEGF) inhibitors have appeared, but they were far from customized treatments due to specific biomarkers.

 

PARP inhibitors were able to perform customized treatment according to biomarkers such as BRCA and homologous recombination deficiency (HRd).

 

In an interview with Dailypharm, Lee Taek-sang, a professor of obstetrics and gynecology at Boramae Hospital, said, "PARP inhibitors have improved ovarian cancer prognosis and changed the treatment paradigm with survival rate.

 

The PARP inhibitors used in Korea are Takeda's Zejula and AstraZeneca's Lynparza.

 

Recently, PARP inhibitors in the U.S.

 

have withdrawn their indications for the fourth or higher treatment of ovarian cancer, but the impact is expected to be minimal as both drugs are used in early treatment such as primary maintenance therapy.

 

◆ Same but different Zejula Lynparza Zejula and Lynparza show some differences in primary maintenance therapy.

 

Basically, both drugs are used as maintenance therapy in platinum-sensitive patients, while Zejula can be used regardless of BRCA or HRd, while Lynparza can be used alone in BRCA-positive and in combination with Avastin in HRd-positive patients.

 

Professor Lee said, "Lynparza is also likely to be effective in patients without BRCA or HRd mutations, but there is no indication because it was only for patients with BRCA mutations in the clinical trial on the basis of permission." Zejula added that through large-scale phase 3 clinical trials, consistent data are also available in BRCA-negative and HRp (homologous recombinant negative) patients.

 

Health insurance benefits apply only to BRCA-positive patients on both drugs.

 

In addition, when Lynparza is used as primary maintenance therapy, the benefit is applied only up to two years after initial administration, while Zejula can be used continuously until recurrence.

 

This is because the follow-up period was only up to two years in clinical trials on which Lynparza permits were based.

 

In addition, the two drugs also show differences in the number, dose, and safety profile of the drug.

 

This difference is the standard for selecting drugs in the clinical field.

 

Professor Lee said, "Lynparza is taken twice a day, but Zejula is taken only once a day.

 

In addition, Zejula has data that shows consistent treatment effects even with adaptive doses, he said.

 

"The more worrisome part is the benefit recognition period, and patients taking Lynparza are converted to non-reimursement two years after the benefit is applied," he said.

 

◆What is the direction of ovarian cancer treatment? The disappointing part of the benefit standard is the BRCA-negative patient.

 

Zejula also demonstrated consistent benefits in BRCA-negative patients but was not recognized for benefit adequacy in the group.

 

Professor Lee said, "It is certain that Zejula is helpful in this patient group, but the patient has to make a difficult decision because the drug has to be used as a non-payment." For HRd biomarkers, improving the diagnostic environment is a priority.

 

Unlike the BRCA test, the HRd test method has not yet been commercialized, so it is limited to some institutions on a trial basis.

 

The cost of the test also amounts to 5 million won.

 

It is judged that more patients will be able to benefit from PARP inhibitors only when an environment where HRd tests can be freely used at the medical site is created.

 

Professor Lee said, "If the results show that PARP inhibitor + Avastin combination therapy is more meaningful, the treatment pattern and paradigm can be changed again.

 

In this case, the drug will be selected in consideration of the side effects and cost problems caused by Avastin, he said.

 

"If the non-inferiority results show that there is no significant difference between the two treatments, it is expected to be a landslide victory for PARP inhibitor alone."