AstraZeneca’s Lynparza (ingredient: olaparib) obtained additional indication for combination therapy with bevacizumab in the first-line maintenance treatment of ovarian cancer in Korea....The Ministry of Food and Drug Safety granted the use of Lynparza in combination with bevacizumab as the maintenance therapy for adult patients with HRD-positive advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who responded to the first-line combo of platinum-based chemotherapy and bevacizumab.

AstraZeneca and MSD’s Lynparza (olaparib) has been approved in Japan for the treatment of advanced ovarian, prostate and pancreatic cancers….The three approvals authorise Lynparza for: maintenance treatment after 1st-line chemotherapy containing bevacizumab (genetical recombination) for patients with homologous recombination repair deficient (HRD) ovarian cancer...The approval as 1st-line maintenance treatment with bevacizumab for patients with HRD-positive advanced ovarian cancer is based on a biomarker subgroup analysis of the PAOLA-1 Phase III trial...

AstraZeneca and MSD’s Lynparza (olaparib) has been approved in the European Union (EU) for the 1st-line maintenance treatment with bevacizumab of patients with homologous recombination deficient (HRD)-positive advanced ovarian cancer.

Food and Drug Administration (FDA) has approved LYNPARZA in combination with bevacizumab as a first-line maintenance treatment of adult patients with advanced epithelial ovarian...with homologous recombination deficiency (HRD) positive status defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability.

Lynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated: Ovarian cancer….in combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either....genomic instability.

Lynparza in combination with bevacizumab is indicated for the...maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinumbased chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either...a deleterious or suspected deleterious BRCA mutation

Ovarian Cancer...Maintenance Therapy...Category 1 added to bevacizumab + olaparib for HR deficient

Olaparib plus bevacizumab is recommended for use within the Cancer Drugs Fund as an option for maintenance treatment of advanced (International Federation of Gynecology and Obstetrics [FIGO] stages 3 and 4) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer in adults when...the cancer is associated with homologous recombination deficiency (HRD).

In lower-risk HRD-positive patients, the HR for progression-free survival was 0.26 (95% CI 0.15 to 0.45), with 5-year progression-free survival of 72% with olaparib plus bevacizumab versus 28% with bevacizumab alone; and the HR for overall survival was 0.31 (95% CI 0.14 to 0.66), with 5-year overall survival of 88% versus 61%, respectively.

The phase III PAOLA-1/ENGOT-ov25 study (NCT02477644) showed that addition of olaparib to bevacizumab maintenance improved progression-free survival (PFS) in patients with newly diagnosed advanced ovarian cancer....After median follow-up of 22.1 months, median PFS was 21.6 months with olaparib versus 16.6 months with placebo in the older population (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.41-0.75), comparable with the younger population (median 22.9 versus 16.9 months; HR 0.61, 95% CI 0.49-0.77). PFS benefits were observed in patients with a BRCA mutation or homologous recombination deficiency-positive tumours.

In PAOLA-1, maintenance olaparib plus bevacizumab provided a substantial PFS benefit in HRD-positive patients with a reduction of risk of progression or death of 61% in the higher-risk group and of 85% in the lower-risk group compared with bevacizumab alone.

Of 806 randomized pts, 292 (36%) were ≥65 y (Table). Median age: older pts, 69 y (range 65–87 y); younger pts, 56 y (range 26–64 y). A lower proportion of older vs younger pts had an ECOG performance status of 0 (62% vs 75%), upfront surgery (39% vs 57%) and, of pts who had upfront surgery, a lower proportion had complete macroscopic resection (54% vs 62%). Older pts were less likely to have a BRCA1/2 mutation (BRCAm) (17% vs 36% of younger pts) or a homologous recombination deficiency (HRD)-positive status (36% vs 55%) and were more likely to be HRD-negative (46% vs 28%). Data cut off was 22 March 2019. After a median follow-up (in censored pts) of 22.1 months (mo) in older pts and 24.0 mo in younger pts, similar PFS was observed in the older and younger pt subgroups (Table). In older pts, greater PFS benefits with olaparib were seen in those with a BRCAm or who were HRD-positive...Despite a lower rate of complete surgical debulking, older pts achieved a similar PFS benefit vs younger pts (including in the BRCAm and both HRD positive cohorts) when olaparib was added to first-line maintenance bev, with a comparable safety profile.

Median follow-up for PFS and PFS2 was respectively 24.8 and 37.2 mo in HRD+ stage III pts and 24.0 and 37.0 mo in HRD+ stage IV pts…. In the PAOLA-1 study, maintenance olaparib + bev provided a PFS and PFS2 benefit over pbo + bev in HRD+ pts…

...AstraZeneca and Merck, known as MSD outside the United States and Canada, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending LYNPARZA for the maintenance treatment of adult patients with advanced (FIGO stages III and IV) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy in combination with bevacizumab and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either a BRCA1/2 mutation and/or genomic instability....The positive opinion was based on a biomarker subgroup analysis of the Phase 3 PAOLA-1 trial, whichwas published in The New England Journal of Medicine....The addition of LYNPARZA to bevacizumab improved progression-free survival (PFS) to a median of 37.2 months vs. 17.7 months with bevacizumab alone in patients with HRD-positive advanced ovarian cancer.

Olaparib + bev provided a statistically significant reduction in the risk of second progression or death vs placebo + bev (ITT analysis; HR 0.78; 95% CI 0.64 -0.95; P=0.0125).... Adding maintenance olaparib to bev provided a benefit beyond first progression, with a substantial PFS2 benefit in tBRCAm and HRD-positive pts. The statistically significant improvement in PFS2 seen with olaparib + bev vs placebo + bev was supported by a similar TSST benefit.

In PAOLA-1, maintenance bev alone achieves a substantial ORR in pts with residual disease after initial therapy. Adding olaparib improved ORRs compared with bev. In both maintenance arms, BRCAm and HRD-positive pts are deriving the greatest benefit.

Addition of olaparib to bev maintenance therapy following 1L PCh plus bev led to a statistically significant and clinically meaningful PFS benefit in pts with advanced OC. The PFS benefit in pts with a tBRCAm and in HRD-positive pts was substantial.

Eligible patients were 18 years of age or older and had newly diagnosed advanced (International Federation of Gynecology and Obstetrics [FIGO] stage III or IV), high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian-tube cancer....The duration of investigator-assessed progression-free survival was significantly longer in the olaparib group than in the placebo group (median, 22.1 months vs. 16.6 months; hazard ratio for disease progression or death, 0.59; 95% CI, 0.49 to 0.72; P<0.001)

...Patients with histologically confirmed high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer and HRD-positive tumor according to the Myriad Mychoice CDx Plus evaluation....

...Concordance in HRD status identification between VHIO-CARD-300 test and SOPHiA DDM™ Dx HRD Solution...

In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR=0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR=0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%)...Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer.

Pts with high-grade AOC, in response after PBC + bev, were randomized 2:1 to ola tablets (300 mg bid; up to 24 months [mo]) + bev (15 mg/kg q3w; 15 mo total) or placebo [pbo] + bev....In HRD+ pts, OS was prolonged with ola + bev (HR 0.62, 95% CI 0.45–0.85; OS at 5 y, 65.5 vs 48.4%), with benefit in HRD+ pts with or without a tumour BRCAm (tBRCAm; Table)...ola + bev provided a clinically meaningful improvement in OS for 1L HRD+ pts with and without a tBRCAm, confirming ola + bev as standard of care in this setting.