...the Ministry of Food and Drug Safety approved Lynparza as adjuvant therapy for gBRCA-mutated HER2-negative high-risk early-stage breast cancer and as combination therapy for metastatic castration-resistant prostate cancer with abiraterone and prednisolone....The approval was based on the OlympiA study in the case of gBRCA-mutated HER2-negative high-risk early-phase breast cancer patients...

AstraZeneca and MSD’s Lynparza (olaparib) has been approved in Japan for the adjuvant treatment of patients with BRCA-mutated (BRCAm), HER2-negative early breast cancer at high risk of recurrence....This approval by the Japanese Ministry of Health, Labour, and Welfare was based on results from the OlympiA Phase III trial...

The Drugs Controller General of India (DCGI) has approved AstraZenca’s Lynparza (Olaparib) as a monotherapy for the adjuvant treatment of adult patients with BRCA-mutated HER2- negative high-risk early breast cancer...

Health Canada has granted a Notice of Compliance with Conditions (NOC/c) for Lynparza® (olaparib) for the adjuvant treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy....This approval was granted under Health Canada's accelerated review pathway and based on results from the OlympiA Phase III trial...

AstraZeneca and Merck...announced that the European Commission (EC) has approved LYNPARZA as monotherapy or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline BRCA1/2 mutations (gBRCAm), who have human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy....This approval by the EC was based on results from the Phase 3 OlympiA trial...In OlympiA, LYNPARZA demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival (IDFS), reducing the risk of invasive breast cancer recurrences, new cancers, or death by 42% (HR=0.58; [99.5% CI, 0.41-0.82]; p<0.0001) versus placebo.

Lynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated...for the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm human epidermal growth factor receptor 2 (HER2)-negative high risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza.

AstraZeneca and Merck & Co...announced that Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) has approved Lynparza (olaparib) tablets for use in patients with unresectable or recurrent BRCA-mutated (BRCAm), human epidermal growth factor receptor 2 (HER2) negative breast cancer who have received prior chemotherapy.

Lynparza is indicated as monotherapy for the treatment of adult patients with germline BRCA1/2-mutations, who have HER2 negative locally advanced or metastatic breast cancer. Patients should have previously been treated with an anthracycline and a taxane in the (neo)adjuvant or metastatic setting unless patients were not suitable for these treatments

LYNPARZA is indicated as monotherapy for the...treatment of adult patients with germline BRCA-mutated HER2-negative metastatic breast cancer who have previously been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting.

Lynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:...for the treatment of adult patients with deleterious or suspected deleterious gBRCAm, HER2-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza.

Olaparib (alone or with endocrine therapy) is recommended, within its marketing authorisation, as an option for the adjuvant treatment of HER2-negative high-risk early breast cancer that has been treated with neoadjuvant or adjuvant chemotherapy in adults with germline BRCA1 or 2 mutations.

The updated recommendation...For patients with early-stage, human epidermal growth factor receptor 2 (HER2)–negative breast cancer with high risk of recurrence and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, one year of adjuvant olaparib should be offered after completion of (neo)adjuvant chemotherapy and local treatment, including radiation.

While olaparib and talazoparib are FDA indicated in HER2-negative disease, the panel supports use in any breast cancer subtype associated with a germline BRCA1 or BRCA2 mutation.

Recommendations...Patients with HER2-negative MBC and germline pathogenic or likely pathogenic variants in BRCA1 or BRCA2 should be offered treatment with a PARP inhibitor (olaparib or talazoparib) independent of HR status...

In this open-label trial, pts with germline or somatic BRCAm, HER2-negative mBC received olaparib…Efficacy outcomes with olaparib were consistent across ER expression subgroups (Table)....Real-world results of the phase IIIb LUCY trial support the clinical effectiveness of olaparib in pts with gBRCAm, HER2-negative mBC, regardless of ER expression level.

Patients with germline BRCA1 and/or BRCA2 pathogenic variants and HER2-negative, high-risk early breast cancer who had received neoadjuvant or adjuvant chemotherapy and completed local treatment were eligible. Patients were randomized 1:1 to receive olaparib or placebo for 1 year....At the first pre-specified interim analysis (median follow-up: 2.9 years), hazard ratios (HRs) for adjuvant olaparib compared with placebo were 0.5 for IDFS (95% confidence interval [CI] 0.18–1.24) and 0.41 for DDFS (95% CI 0.11–1.16).

Investigator-assessed median PFS was longer across all subgroups with olaparib (range, 4.3-11.0 months) vs TPC (range, 2.9-5.5 months) and consistent with those derived from the FAS….Confirmed responses were numerically higher in each subgroup in the olaparib arm than in the TPC arm, at approximately double the rate in most subgroups...These findings support the use of olaparib monotherapy for a broad spectrum of patients with gBRCAm, HER2-negative mBC.

Four-year OS was 89.8% in the olaparib-group and 86.4% in the placebo-group (Δ 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for olaparib-group versus placebo-group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively....With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals.

AstraZeneca and MSD’s Lynparza (olaparib) has been recommended for marketing authorisation in the European Union (EU) as monotherapy or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline BRCA1/2 mutations (gBRCAm) who have HER2-negative high-risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on results from the OlympiA Phase III trial...

Eligible adults had germline (g) or somatic (s) BRCA1- and/or BRCA2-mutated (BRCAm), HER2-negative mBC...mPFS: 8.2 months (95% CI 7.0–9.2; 208 events, 81.6%). mOS: 24.9 months (95% CI 21.1–27.9; 142 events, 55.7%). OS rate at 30 months: 41.7% (95% CI 35.2–48.1)....The benefit of olaparib was similar across HR status and treatment lines. mOS was longer than reported in OlympiAD. No new safety signals were observed. These results strongly support olaparib as a chemotherapy-free alternative for gBRCAm, HER2-negative mBC.

AstraZeneca and Merck...announced additional positive results from the Phase 3 OlympiA trial. In OlympiA, LYNPARZA demonstrated a statistically significant improvement in overall survival (OS) versus placebo for the adjuvant treatment of patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy.

AstraZeneca’s supplemental New Drug Application (sNDA) for Lynparza (olaparib) has been accepted and granted Priority Review in the US for the adjuvant treatment of patients with BRCA-mutated (BRCAm) HER2-negative high-risk early breast cancer who have already been treated with chemotherapy either before or after surgery.

At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease–free survival was 85.9% in the olaparib group and 77.1% in the placebo group...95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001)....Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo.

Of 563 patients screened, 252 patients with gBRCAm were enrolled and received at least one dose of olaparib....Olaparib was clinically effective in patients with gBRCAm, HER2-negative mBC...

Pts were randomized 1:1 to 1 year of continuous oral OL (300 mg BID) or placebo (PL)....Adjuvant OL following ACT or NACT significantly improved IDFS and DDFS with acceptable toxicity in pts with gBRCAm and high-risk HER2-negative EBC.

AstraZeneca and Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced the Phase 3 OlympiA trial for LYNPARZA will move to early primary analysis and reporting following a recommendation from the Independent Data Monitoring Committee (IDMC)....Based on the planned interim analysis, the IDMC concluded that the trial crossed the superiority boundary for its primary endpoint of invasive disease-free survival (iDFS) versus placebo in the adjuvant treatment of germline BRCA-mutated (gBRCAm), high-risk human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer following definitive local treatment and neoadjuvant or adjuvant chemotherapy.

All patients were randomized 2:1 to olaparib tablets...The prevalence of gBRCAm in the OlympiAD Asian subgroup screened for study recruitment was 13.5%. Asian patients in the olaparib arm achieved longer median progression-free survival, assessed by blinded independent central review, versus the chemotherapy TPC arm (5.7 vs 4.2 months; HR = 0.53 [95% CI: 0.29-0.97]), which was consistent with findings in the global OlympiAD study population.

This Phase IIIb, open-label, single-arm study of olaparib 300 mg twice-daily, enrolled pts with HER2- gBRCAm MBC.…Median total treatment duration: 7.9 months (mo; range 0.2-20.0). Median PFS: 8.1 mo (95% confidence interval [CI] 6.9, 8.7; 166 events [65.9%])....Interim results in this real-world population of pts with HER2- gBRCAm MBC were consistent with the OlympiAD study, and support olaparib as a chemotherapy-free alternative treatment for pts with gBRCAm advanced BC.

Among patients with HER2-negative metastatic breast cancer and a germline BRCA mutation, olaparib monotherapy provided a significant benefit over standard therapy; median progression-free survival was 2.8 months longer and the risk of disease progression or death was 42% lower with olaparib monotherapy than with standard therapy.

NON SUPPORTIVE: HR for OS with olaparib versus TPC in prespecified subgroups were: prior chemotherapy for mBC [no (first-line setting): 0.51, 95% CI 0.29-0.90; yes (second/third-line): 1.13, 0.79-1.64]; receptor status (triple negative: 0.93, 0.62-1.43; hormone receptor positive: 0.86, 0.55-1.36); prior platinum (yes: 0.83, 0.49-1.45; no: 0.91, 0.64-1.33). While there was no statistically significant improvement in OS with olaparib compared to TPC...

...Assess the efficacy of olaparib in HER2-negative early Breast Cancer and HRD (BRCA 1/2 mutations and/or HRD positive)...

...To be regarded as BRCA1/2 (+ve), the patient must have a mutation that is predicted...

The open-label, single-arm LUCY trial of olaparib (300 mg, twice daily) enrolled adults with gBRCAm or somatic BRCA-mutated (sBRCAm), HER2-negative mBC….In the gBRCAm cohort, median investigator-assessed PFS (primary endpoint) was 8.18 months and median OS was 24.94 months....The LUCY patient population reflects a real-world population in line with the licensed indication of olaparib in mBC. These findings support the clinical effectiveness and safety of olaparib in patients with gBRCAm, HER2-negative mBC.

We analyzed data of patients with HER2-ve ABC with germline and/or somatic mutation of BRCA 1 or BRCA 2 or in the Homologous Recombination Repair genes, treated with olaparib or talazoparib in daily clinical practice...The rwORR was 47.0%, and the median rwPFS1 was 7.77 months (CI95% 5.67-14.7)....

In all analysed populations, olaparib was associated with improved median PFS vs TPC or capecitabine (Table). Safety was aligned with published data. Table: 200P…Olaparib was associated with longer PFS vs TPC or capecitabine with an acceptable safety profile in gBRCAm HER2-negative mBC. These results may aid in the optimal treatment selection for patients with gBRCAm BC.

Patients with gBRCAm, human epidermal growth factor receptor 2-negative mBC, who had received ≤2 lines of chemotherapy for metastatic disease, were randomised 2:1 to olaparib...In the overall population (302 patients; 76.8% maturity), median OS was 19.3 months for olaparib and 17.1 months for TPC (hazard ratio 0.89, 95% confidence interval 0.67-1.18); median follow-up was 18.9 and 15.5 months, respectively. Three-year survival was 27.9% for olaparib versus 21.2% for TPC.

68 pts received PO and 37 PCb....Overall, pCR rates were higher in pts with BRCA1/2 mutations than in pts without (62.7% vs. 41.3%; P=0.047).

Olaparib monotherapy provided a statistically significant increment of PFS in almost 2/3 (63%) of heavily pretreated MBC pts harboring gBRCAm and lBRCAm.