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Imfinzi approved in Japan for unresectable Stage III non-small cell lung cancer

On July 2, 2018 AstraZeneca and MedImmune, its global biologics research and development arm, reported that the Japanese Ministry of Health, Labour and Welfare approved Imfinzi (durvalumab) as maintenance therapy after definitive chemoradiation therapy (CRT) in locally-advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, JUL 2, 2018, View Source [SID1234527536]).

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Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit said: "Non-small cell lung cancer is a leading cause of death in Japan, and we are dedicated to bringing new treatment options to patients as quickly as possible. As the only immunotherapy approved in the curative-intent, Stage III lung cancer setting, Imfinzi has the potential to change the treatment paradigm for patients diagnosed with this disease."

The approval of Imfinzi is based on positive progression-free survival (PFS) data from the Phase III PACIFIC trial in unresectable Stage III NSCLC. In the trial, Imfinzi demonstrated an improvement in median PFS of 11.2 months compared to placebo. Imfinzi improved other meaningful outcomes such as time to distant metastasis or death and overall response rates. Detailed results of the PACIFIC trial were published in the New England Journal of Medicine (NEJM).

1 Blinded Independent Central Review (BICR).

2 Among the ITT population, 7% in the Imfinzi arm and 10% in the placebo arm had non-measurable disease as assessed by BICR according to RECIST v1.1.

3 Stratified by sex, age, and smoking history.

4 Pike estimator.

5 Compared with allocated α of 0.0104 (Lan DeMets spending function approximating O’Brien Fleming boundary) for interim analysis.

The incidence and severity of adverse events were comparable for patients receiving Imfinzi vs. patients receiving placebo. The most frequent adverse reactions were rash which occurred in 73 subjects (15.4%), hypothyroidism which occurred in 50 subjects (10.5%), diarrhoea which occurred in 46 subjects (9.7%) and interstitial lung disease which occurred in 46 subjects (9.7%).

In May 2018, AstraZeneca announced that the PACIFIC trial met its second primary endpoint, showing statistically-significant and clinically-meaningful overall survival (OS) in patients receiving Imfinzi compared to placebo. Full results will be presented at a forthcoming medical meeting.

Imfinzi is also approved in the US, Canada, Switzerland and India based on the Phase III PACIFIC trial. Regulatory reviews in the EU and other jurisdictions are ongoing with an EU decision expected in the second half of 2018.

About Stage III NSCLC

Stage III (locally-advanced) NSCLC is commonly divided into three sub-categories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally and the possibility of surgery. Stage III disease is different from Stage IV disease, when the cancer has spread (metastasised) to distant organs, as Stage III is currently treated with curative intent.

Stage III NSCLC represents approximately one-third of NSCLC incidence and was estimated to affect around 105,000 patients in the top-eight countries (China, France, Germany, Italy, Japan, Spain, UK, US) in 2017. The majority of Stage III NSCLC patients are diagnosed with unresectable tumours. Before the PACIFIC trial, the standard of care was chemotherapy and radiation therapy, followed by active surveillance to monitor for progression.

About PACIFIC

The PACIFIC trial is a randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi as treatment in patients with Stage III unresectable NSCLC whose disease has not progressed following platinum-based chemoradiation therapy (CRT).

The trial has been conducted in 235 centres across 26 countries involving 713 patients. The primary endpoints of the trial are PFS and OS, and secondary endpoints include landmark PFS and OS, objective response rate, and duration of response.

About Imfinzi

Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with chemotherapy, radiation therapy, small molecules, and tremelimumab, an anti-CTLA4 monoclonal antibody, as a 1st-line treatment for patients with NSCLC, small cell lung cancer, locally-advanced or metastatic urothelial carcinoma, head and neck cancer and other solid tumours.

Lynparza approved in Japan for BRCA-mutated metastatic breast cancer

On July 2, 2018 AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US (Merck: known as MSD outside the US and Canada) reported 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 (Press release, AstraZeneca, JUL 2, 2018, View Source [SID1234527535]). Patients are selected for therapy based on an approved companion diagnostic.

Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit at AstraZeneca, said: "Earlier this year, Lynparza became the first PARP inhibitor available in Japan for advanced ovarian cancer. Now patients in Japan with BRCA-mutated, metastatic breast cancer will also have the opportunity to benefit from Lynparza. This latest approval underlines our ongoing efforts to make Lynparza available across multiple cancers as quickly as possible to patients around the world."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "Metastatic breast cancer is a complex disease with remaining unmet medical need. This approval is significant for breast cancer patients as the evaluation of BRCA mutations, in addition to hormone receptor and HER2 status, now becomes an important step in the management of the disease."

The approval is based on data from the randomised, open-label, Phase III OlympiAD trial, which tested Lynparza vs chemotherapy. Patients were selected for therapy based upon a confirmed BRCA mutation. In the trial, Lynparza significantly prolonged progression-free survival (PFS) compared with chemotherapy, reducing the risk of disease progression or death by 42% (HR 0.58; 95% CI 0.43-0.80; p=0.0009, median PFS was 7.0 months with Lynparza vs 4.2 months with chemotherapy).

Lynparza was generally well tolerated with the majority of adverse events (AEs) reported as mild to moderate with a lower rate of Grade 3 or higher AEs compared with chemotherapy (36.6% vs 50.5%). The most common AEs were nausea (50.2%), anaemia (32.2%) and fatigue (22.4%).

Lynparza is also approved in Japan as maintenance treatment for women with platinum-sensitive relapsed ovarian cancer, regardless of BRCA mutation status. In Japan, the co-promotion of Lynparza by both companies will begin on 1 July 2018.

About OlympiAD

OlympiAD was a randomised, open-label, multicentre Phase III trial assessing the efficacy and safety of Lynparza tablets (300 mg twice daily) compared to physician’s choice of chemotherapy (capecitabine, eribulin, or vinorelbine) in 302 patients with HER2-negative metastatic breast cancer with germline BRCA1 or BRCA2 mutations, which are confirmed or suspected to be deleterious. The international trial was conducted in 19 countries across Europe, Asia, North America and South America.

Patients in the OlympiAD trial had HER2-negative gBRCA1- or gBRCA2-mutated breast cancer, which was hormone-receptor positive (HR+) or triple negative, and received Lynparza for metastatic disease. Approximately half of the patients in the Lynparza and chemotherapy arm of the trial were HR+ (n=152), and approximately half were triple negative (n=150). Among the 205 patients treated with Lynparza, the median age was 44 years (range: 22 to 76). Before enrolment, patients had prior treatment with an anthracycline (unless contraindicated) and a taxane chemotherapy either in the neoadjuvant, adjuvant or metastatic setting and no more than two prior lines of chemotherapy for metastatic disease. HR+ patients had received at least one endocrine medicine or were not eligible for endocrine medicines. Prior treatments with endocrine medicines were not counted as prior lines of chemotherapy.

The primary endpoint of the trial was PFS as measured by a Blinded Independent Central Review. Secondary endpoints included overall survival, time to second progression or death, objective response rate, and effect on health-related quality of life.

About BRCA mutations

BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role in maintaining the genetic stability of cells. When either of these genes is mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.

About breast cancer in Japan

In Japan, breast cancer is the fifth leading cause of death among women.[i] In Japanese women, breast cancer incidence peaks in the late forties, whereas in the US and Europe the peak incidence is in women over 60 years of age.[ii] Despite more treatment options becoming available during the past three decades, there is currently no cure for patients diagnosed with metastatic (Stage IV) breast cancer.[iii] In Japan, 5-year and 10-year relative survival rates for patients with Stage IV breast cancer are as low as 32.6% and 15.6%, respectively.[iv] Therefore, the primary aim of treatment is to slow progression of the disease for as long as possible and improve or maintain a patient’s quality of life.5

About Lynparza

Lynparza (olaparib) is the first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Specifically, in vitro studies have shown that Lynparza-induced cytotoxicity may involve inhibition of PARP-enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death. Lynparza is being tested in a range of DDR-deficient tumour types.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is approved for advanced ovarian cancer and metastatic breast cancer and has been used in over 20,000 patients. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor and AstraZeneca and MSD are working together to deliver it as quickly as possible to more patients across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

Compugen Announces FDA Clearance of IND Application for
COM701, a First-in-Class Immuno-Oncology Therapeutic Antibody

On July 2, 2018 Compugen Ltd. (Nasdaq: CGEN), a clinical-stage cancer immunotherapy company and a leader in predictive target discovery, reported that the U.S. Food and Drug Administration (FDA) has removed the clinical hold on its investigational new drug (IND) application for COM701, a first-in-class immuno-oncology therapeutic antibody targeting PVRIG in patients with advanced solid tumors, and informed the Company it may initiate the clinical study (Press release, Compugen, JUL 2, 2018, View Source [SID1234527529]).

"Today is a significant milestone for Compugen, having received clearance from the FDA to advance our lead immuno-oncology program into the clinic. COM701 is a first-in-class drug opportunity that was developed by Compugen from discovery of the drug target by computer prediction through preclinical development, to IND clearance," stated Anat Cohen-Dayag, PhD, President and CEO of Compugen. "We believe the COM701 preclinical data suggest that targeting PVRIG may effectively stimulate an anti-tumor immune response in certain cancers such as breast, endometrial, ovarian and lung, and specifically in patient populations that are unresponsive to current checkpoint inhibitors."

"The PVRIG pathway, a new pathway on which we have shed light, is part of a larger complex immuno-oncology biological axis involving the TIGIT and PD-1 pathways. By targeting this pathway, our COM701 program clearly presents a differentiated profile from other drug targets and combination options in the clinic. We are confident we are the only company with an anti-PVRIG candidate available for clinical testing, either as a single agent and in combination with a PD-1 and TIGIT inhibitors, and we are excited to initiate patient dosing with COM701 in a multicenter Phase 1 trial, early in the fall," Dr. Cohen-Dayag added.

"We worked closely with the FDA in connection with this IND application and are eager to evaluate COM701 in a clinical setting," said Henry Adewoye, MD, Chief Medical Officer of Compugen. "We received positive feedback from leading clinical investigators in the field of immuno-oncology who share our excitement for the potential role of the PVRIG pathway in immuno-oncology and our overall clinical program and strategy. We look forward to collaborating with them on this trial."

Under this IND, the Company intends to initiate a first-in-human Phase 1 study in patients with advanced solid tumors and for whom standard of care therapies are currently ineffective. The clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of COM701 as monotherapy and in combination with a PD-1 inhibitor. The Phase 1 trial is planned to be conducted at multiple centers in the United States and site initiation activities are currently underway.

About COM701
COM701 is a humanized hybridoma antibody that binds with high affinity to PVRIG, a novel B7/CD28-like immune checkpoint target candidate discovered by Compugen, blocking its interaction with its ligand, PVRL2. Blockade of PVRIG by COM701 has demonstrated potent, reproducible enhancement of T cell activation, consistent with the desired mechanism of action of activating T cells in the tumor microenvironment to generate anti-tumor immune responses. In addition, COM701 combined with antagonist anti-PD-1 antibodies has demonstrated synergistic effects on human T cell stimulation, indicating the potential of these combinations to further enhance immune response against tumors.

Preclinical data for COM701 suggest that PVRIG may be a dominant checkpoint in diverse patient populations with tumors that express elevated PVRL2 as compared to expression of the TIGIT ligand PVR. This include patients with breast, endometrial, and ovarian cancers. In addition, expression studies show that PVRIG and TIGIT, and their respective ligands, are expressed in a broad variety of tumor types, such as those noted above, as well as lung, kidney, and head & neck cancers. In these tumors the blockade of both TIGIT and PVRIG may be required to sufficiently stimulate an anti-tumor immune response, with or without additional PD-1 pathway blockade.

Celgene Corporation to Announce Second Quarter 2018 Results on July 26, 2018

On July 2, 2018 Celgene Corporation (NASDAQ: CELG) reported that it will host a conference call and live audio webcast on Thursday, July 26, 2018 at 9 a.m. ET to discuss second quarter 2018 financial and operational results (Press release, Celgene, JUL 2, 2018, View Source [SID1234527528]). The webcast can be accessed from the Investor Relations page at www.celgene.com.

LYNPARZA® (olaparib) Approved in Japan for BRCA-Mutated Metastatic Breast Cancer

On July 2, 2018 AstraZeneca and Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported 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 (Press release, Merck & Co, JUL 2, 2018, View Source [SID1234527525]). Patients are selected for therapy based on an approved companion diagnostic.

Dave Fredrickson, executive vice president, head of the oncology business unit at AstraZeneca, said, "Earlier this year, LYNPARZA became the first PARP inhibitor available in Japan for advanced ovarian cancer. Now patients in Japan with BRCA-mutated, metastatic breast cancer will also have the opportunity to benefit from LYNPARZA. This latest approval underlines our ongoing efforts to make LYNPARZA available across multiple cancers as quickly as possible to patients around the world."

Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, "Metastatic breast cancer is a complex disease with remaining unmet medical need. This approval is significant for breast cancer patients as the evaluation of BRCA mutations, in addition to hormone receptor and HER2 status, now becomes an important step in the management of the disease."

The approval is based on data from the randomized, open-label, Phase 3 OlympiAD trial, which tested LYNPARZA versus chemotherapy. Patients were selected for therapy based upon a confirmed BRCA mutation. In the trial, LYNPARZA significantly prolonged progression-free survival (PFS) compared with chemotherapy, reducing the risk of disease progression or death by 42 percent (HR=0.58 [95% CI, 0.43-0.80]; p=0.0009). Median PFS was 7.0 months with LYNPARZA versus 4.2 months with chemotherapy.

LYNPARZA was generally well tolerated, with the majority of adverse events (AEs) reported as mild to moderate with a lower rate of Grade ≥3 AEs compared with chemotherapy (36.6% vs 50.5%). The most common AEs were nausea (50.2%), anemia (32.2%) and fatigue (22.4%).

LYNPARZA is also approved in Japan as maintenance treatment for women with platinum-sensitive relapsed ovarian cancer, regardless of BRCA mutation status. In Japan, the co-promotion of LYNPARZA by both companies began on July 1, 2018.

Important Safety Information

Contraindications

There are no contraindications for LYNPARZA.

Warnings and Precautions

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some also had a history of more than one primary malignancy or of bone marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals,

LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

Females

Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

Males

Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

Adverse Reactions—Maintenance Setting

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA in the maintenance setting for SOLO-2: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), and decreased appetite (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

Adverse Reactions—Advanced gBRCAm Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of

LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue (including asthenia) (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer (pooled from 6 studies) were: decrease in hemoglobin (90%), increase in mean corpuscular volume (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).

Adverse Reactions—gBRCAm, HER2-Negative Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).

Drug Interactions

Anticancer Agents: Clinical studies of LYNPARZA in combination with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be co-administered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers when using LYNPARZA. If a moderate inducer cannot be avoided, there is a potential for decreased efficacy of LYNPARZA.

Use In Specific Populations

Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

Hepatic Impairment: No adjustment to the starting dose is required in patients with mild hepatic impairment (Child-Pugh classification A). There are no data in patients with moderate or severe hepatic impairment.

Renal Impairment: No adjustment to the starting dose is necessary in patients with mild renal impairment (CLcr=51-80 mL/min). In patients with moderate renal impairment (CLcr=31-50 mL/min), reduce the dose to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

Indications

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.

For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

In patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have previously 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 treatment. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Please see complete Prescribing Information, including Patient Information (Medication Guide).

About OlympiAD

OlympiAD was a randomized, open-label, multi-center Phase 3 trial assessing the efficacy and safety of LYNPARZA tablets (300 mg twice daily) compared to physician’s choice of chemotherapy (capecitabine, eribulin, or vinorelbine) in 302 patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer with germline BRCA1 (gBRCA1) or BRCA2 (gBRCA2) mutations, which are confirmed or suspected to be deleterious. The international trial was conducted in 19 countries across Europe, Asia, North America and South America.

Patients in the OlympiAD trial had HER2-negative gBRCA1- or gBRCA2-mutated breast cancer, which was hormone receptor positive (HR+) or triple negative, and received LYNPARZA for metastatic disease. Approximately half of the patients in the LYNPARZA and chemotherapy arm of the trial were HR+ (n=152) and approximately half were triple negative (n=150). Among the 205 patients treated with LYNPARZA, the median age was 44 years (range, 22 to 76). Before enrollment, patients had prior treatment with an anthracycline (unless contraindicated) and a taxane chemotherapy either in the neoadjuvant, adjuvant or metastatic setting, and no more than two prior lines of chemotherapy for metastatic disease. HR+ patients had received at least one endocrine medicine or were not eligible for endocrine medicines. Prior treatments with endocrine medicines were not counted as prior lines of chemotherapy.

The primary endpoint of the trial was progression-free survival (PFS) as measured by a Blinded Independent Central Review. Secondary endpoints included overall survival (OS), time to second progression or death (PFS2), objective response rate (ORR) and effect on health-related quality of life.

About BRCA Mutations

About Breast Cancer in Japan

In Japan, breast cancer is the fifth leading cause of death among women. In Japanese women, breast cancer incidence peaks in the late forties, whereas in the U.S. and Europe, the peak incidence is in women over 60 years of age. Despite more treatment options becoming available during the past three decades, there is currently no cure for patients diagnosed with metastatic (Stage 4) breast cancer. In Japan, five- and 10-year relative survival rates for patients with Stage 4 breast cancer are as low as 32.6 percent and 15.6 percent, respectively. Therefore, the primary aim of treatment is to slow progression of the disease for as long as possible and improve or maintain a patient’s quality of life.

About LYNPARZA (olaparib) 100 mg tablets

LYNPARZA is the first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Specifically, in vitro studies have shown that LYNPARZA-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death. LYNPARZA is being tested in a range of DDR-deficient tumor types.

LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, is approved for advanced ovarian cancer and metastatic breast cancer and has been used in over 20,000 patients worldwide. LYNPARZA has a broad and advanced clinical trial development program and AstraZeneca and Merck are working together to deliver it as quickly as possible to more patients across multiple cancer types.