Immediate treatment with Lynparza after standard surgery and chemotherapy should be considered for all patients with newly diagnosed stage 3 or 4 ovarian cancer that carries a BRCA gene mutation, even if residual disease remains, researchers have found.
The PARP inhibitor Lynparza (olaparib), given immediately after surgery and chemotherapy to those with recently diagnosed advanced ovarian cancer that expresses a BRCA gene mutation, significantly delays the time until disease worsens in a variety of patient subgroups, according to the findings of a completed study.
The phase 3 SOLO1 trial looked at patients in this population who received surgery followed by platinum-based chemotherapy and then either oral Lynparza maintenance or placebo. In 2018 researchers reported that, at 41 months of follow-up, the time until disease worsened was 13.8 months in those who received a placebo but had not yet been reached in those who received Lynparza. Of the patients receiving Lynparza, 60% remained free of disease progression 36 months after treatment began, compared with 27% of women in the placebo group, the drug’s developer, AstraZeneca, wrote in a press release at the time.
Lynparza was approved by the Food and Drug Administration for that use on Dec. 19, 2018.
On Aug. 4, 2020, researchers released new findings showing that Lynparza maintenance improved health outcomes across all subgroups studied in the trial, even those who had more moderate responses to surgery or chemotherapy, and regardless of which type of BRCA mutation they had. This will help clarify which patients are good candidates for the treatment.
PARP inhibitors disable the ability of cancer cells to repair their own DNA when it gets damaged and tend to work especially well in cancers that already have DNA-repair problems, such as those that express BRCA mutations like ovarian cancers.
The authors noted that most patients with newly diagnosed advanced ovarian cancer that expresses a BRCA gene mutation have no evidence of disease after receiving surgery and chemotherapy, but that 70% of them will experience a disease relapse within three years of diagnosis. After recurrence, they wrote, most patients receive additional multiple lines of treatment and will eventually die as a result of their disease.
Maintenance therapy is given before relapse occurs with the goal of maintaining the health benefits gained from primary treatment.
A total of 391 patients with stage 3 or 4 disease were included in the subgroup analysis, 260 of whom received Lynparza and 130 of whom received placebo. Of those, 123 completed two years of treatment with Lynparza and 35 completed two years of treatment with placebo.
Researchers found that Lynparza maintenance after surgery and chemotherapy, compared with placebo at 41 months after the start of study treatment, reduced the risk of disease progression by 69% in patients who underwent initial surgery; 63% in patients who had surgery in the midst of their treatment with chemotherapy; 56% in those with residual disease after surgery; 67% in patients with no residual disease after surgery; 66% in women with clinical complete response when they started Lynparza; 69% in women with partial response when they started Lynparza; 59% in patients with BRCA1 mutations; and 80% in patients with BRCA2 mutations.
The researchers also reported objective response rates (ORR), meaning the total proportion of women who experienced either a partial or complete response after taking Lynparza. Among the 80 women who had evidence of disease when starting Lynparza, ORR was 43% in the Lynparza arm versus 23% in the placebo arm. Complete responses among women in that population were reported for 28% treated with Lynparza versus 12% treated with placebo. Fifteen percent of the Lynparza patients in that population had partial responses, versus 12% of women treated with placebo.
“Patients with newly diagnosed advanced ovarian cancer achieve substantial benefit from maintenance olaparib treatment regardless of baseline surgery outcome, response to chemotherapy or BRCA mutation type,” the authors concluded. “Despite a large proportion of patients having optimal surgical outcomes and being in complete response after chemotherapy, outcomes after placebo treatment were poor, further supporting the use of maintenance olaparib for all patients regardless of baseline characteristics.”