The UK’s National Institute for Health and Care Excellence has approved olaparib for the maintenance treatment of adult patients with relapsed, platinum-sensitive, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer whose disease responded to platinum-based chemotherapy and harbor BRCA1/2 mutations.
The UK’s National Institute for Health and Care Excellence has approved olaparib (Lynparza) for the maintenance treatment of adult patients with relapsed, platinum-sensitive, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer whose disease responded to platinum-based chemotherapy and harbor BRCA1/2 mutations.1
Before this expanded indication, olaparib was available as a capsule formulation within NHS England and Wales via routine commissioning for patients with relapsed BRCA-mutant ovarian cancer who had received ≥3 lines of chemotherapy. With the updated indication, olaparib is now available as a tablet formulation for these patients, as well as for patients within NHS England via the Cancer Drugs Fund (CDF) if they have had 2 courses of platinum-based chemotherapy.
The new indication is based on findings from the phase III SOLO2 and the phase II Study 19 trials. SOLO2 showed a clinically meaningful and statistically significant improvement in progression-free survival (PFS) at 19.1 months with olaparib compared with 5.5 months with placebo (HR, 0.30; 95% CI, 0.22-0.41; P <.0001) via investigator assessment. The estimated 2-year PFS rates were 43% and 15%, respectively.2
In Study 19, the risk of progression or death was reduced by 65% with maintenance olaparib versus placebo for women with ovarian cancer, regardless of BRCA status.3
“Clinical trials show that olaparib extends the time until the cancer progresses compared with routine surveillance, regardless of whether the person has a BRCA mutation,” NICE stated in its final appraisal document recommending use of olaparib in this setting. “But the company has offered a commercial arrangement that applies to olaparib tablets when used for people with a BRCA mutation who have had 2 or more courses of platinum-based chemotherapy. This means that olaparib is cost effective only when used for the subgroup of people with a BRCA mutation. For people with a BRCA mutation who have had 3 or more courses of platinum-based chemotherapy, olaparib meets NICE’s end-of-life criteria. It is cost effective for this group of people and is therefore recommended for routine use in the NHS.”
In SOLO2, patients were randomized 2:1 to olaparib as a 300-mg tablet twice daily dose (n = 196) or placebo (n = 99). All patients had relapsed ovarian cancer, confirmed BRCA1/2 mutation, and were in response to their most recent platinum-containing regimen following ≥2 prior systemic regimens. The primary endpoint was investigator-assessed PFS.
The median age was 56 years and baseline characteristics did not differ substantively between treatment groups. Most patients had an ECOG performance status of 0 (83% with olaparib vs 78% for placebo) and 47% of patients had a complete response (CR) to prior chemotherapy. Prior bevacizumab (Avastin) was received by 17% of those in the olaparib group and for 20% of those in the placebo arm. Approximately 40% of patients had received ≥3 prior lines of therapy.
Results also included a prespecified analysis of PFS by a blinded central review committee, which showed a median PFS of 30.2 months for the olaparib group versus 5.5 months for placebo, a 75% reduction in the hazard for progression and death (HR, 0.25; 95% CI, 0.18-0.35; P <.0001).
The 12-month PFS rate was 65% in the olaparib group (95% CI, 57.8%-71.4%) versus 21% in the placebo arm (95% CI, 13.3%-29.6%). PFS also favored olaparib at 24 months (43% vs 15%). For patients with confirmed or suspected deleterious BRCA1/2 mutations (n = 286), PFS was superior for olaparib compared with placebo at 19.3 vs 5.5 months, respectively (HR, 0.33; 95% CI, 0.24-0.44; P <.0001).
In Study 19, patients with platinum-sensitive, recurrent high-grade serous ovarian cancer (n = 265) were randomized to olaparib capsules as 400 mg twice daily (n = 136) or placebo (n = 129). Patients had received ≥2 prior regimens of platinum-based chemotherapy and experienced CR or partial response to their most recent regimen.
The median PFS for patients taking maintenance olaparib was 8.4 months compared with 4.8 months for the control group (HR, 0.35; P <.0001). For those with BRCA mutations, the median PFS was 11.2 versus 4.3 months for placebo, which led to an 82% reduction in the risk of disease progression or death (HR, 0.18; P <.0001).
In the third interim analysis of Study 19, across the full study the median OS was 29.8 months in the olaparib group and 27.8 months in the placebo group (HR, 0.73; 95% CI, 0.55-0.96; nominal P = .02483). In the BRCA mutation group (n = 136), median OS was 34.9 months for the olaparib group and 30.2 months for placebo (HR, 0.62; 95% CI, 0.41-0.94; nominal P = .02480). However, these were not considered to be statistically significant.