PARP inhibitors, which had emerged as the most common targeted therapy for unresectable ovarian cancer, could increase death risk in patients who experienced several chemotherapies, a recent study showed, forcing developers to withdraw their indications.
AstraZeneca reportedly distributed an official notice about the change of permission on Lynpazar (olaparib) to medical experts in the U.S. on Aug. 26.
The content of the notice was that the U.K.-headquartered pharmaceutical company withdrew the “Lynpazar’s indication as a monotherapy for progressive ovarian cancer patients with gBRCA mutations who have received three or more chemotherapies,” as approved by the U.S. Food and Drug Administration.
AstraZeneca’s decision came after the subgroup analysis results for the overall survival (OS) of the SOLO-3 study, a phase 3 clinical trial of Lynpazar, were released.
The SOLO-3 study showed that death risks even increased by 33 percent in the participants who had received three or more chemotherapies compared to those who received existing chemotherapies. Also, in the entire participants who had received two more chemotherapies, the death risks were similar between the Lynpazar-administered group and the chemotherapy group.
The indication withdrawn this time was the “conditional approval” based on objective response rate (ORR) and duration of response (DoR) Lynpazar had shown in Study 42, a phase 2 clinical study on the single group. However, Lynpazar failed to prove survival benefits in the SOLO-3 study, a trial for final confirmation, forcing AZ to withdraw the indication.
Lynpazar is not the only PARP (poly ADP ribose polymerase) inhibitor that withdrew indication for terminally ill patients with extensive treatment experiences.
This past June, Clovis Oncology withdrew Rubraca's (rucaparib) indication for the tertiary treatment of ovarian cancer, and GSK also withdrew Zejula's (niraparib) indication for quarternary or more treatment of ovarian cancer.
Rubraca increased the death risk by 31.3 percent in patients who had received two or more chemotherapies compared to existing chemotherapies in the ARIEL4 study, a phase 3 clinical trial.
Zejula also showed a shorter survival period than chemotherapies in patients without BRCA (breast cancer) mutations. It showed the overall survival median value of 43.6 months, two months longer than chemotherapies, but it was statistically insignificant.
The PARP inhibitor developers’ moves are likely to affect the domestic market, according to industry watchers.
Lynpazar has yet to receive domestic approval for the pertinent indication, and Rubraca also remains an unapproved product, causing no damages. However, Zejula has received approval from the Ministry of Food and Drug Safety for indication to treat quarternary or more ovarian cancer and got insurance coverage, too.
Industry watchers pay attention to whether the ministry and the Health Insurance Review and Assessment Service would begin to verify Zejula’s survival benefits. Takeda Pharmaceutical Korea has the right to the domestic sales of Zejula.