On January 15, 2018 Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) reported that the U.S. Food and Drug Administration (FDA) has approved the use of TRISENOX (arsenic trioxide) injection in combination with tretinoin for the treatment of adults with newly-diagnosed low-risk acute promyelocytic leukemia (APL) whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression (Press release, Teva, JAN 15, 2018, View Source;p=RssLanding&cat=news&id=2326522 [SID1234523123]). The approval was based on a Priority Review by the FDA on data from published scientific literature and a review of Teva’s global safety database for arsenic trioxide.

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"Today’s approval to expand the indication of TRISENOX is a testament to Teva’s commitment to providing solutions to advance cancer care," said Paul Rittman, Senior Vice President and General Manager, Teva Oncology. "This label expansion represents an important benefit as TRISENOX is now an FDA-approved first line treatment option for patients with acute promyelocytic leukemia."

The new indication reinforces the current practice guidelines by the National Comprehensive Cancer Network (NCCN).

Please see the Full Prescribing Information for TRISENOX and the Important Safety Information below including Boxed Warning regarding: DIFFERENTIATION SYNDROME AND CARDIAC CONDUCTION ABNORMALITIES.

TRISENOX (arsenic trioxide) Injection IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME AND CARDIAC CONDUCTION ABNORMALITIES

Differentiation Syndrome: Patients with acute promyelocytic leukemia (APL) treated with TRISENOX have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, weight gain or peripheral edema, hypotension, and renal, hepatic, or multi-organ dysfunction, in the presence or absence of leukocytosis. If differentiation syndrome is suspected, immediately initiate high-dose corticosteroid therapy and hemodynamic monitoring until resolution of signs and symptoms. Temporary discontinuation of TRISENOX may be required.

Cardiac Conduction Abnormalities: Arsenic trioxide can cause QTc interval prolongation, complete atrioventricular block, and a torsade de pointes-type ventricular arrhythmia, which can be fatal. Before initiating therapy, assess the QTc interval, correct pre-existing electrolyte abnormalities, and consider discontinuing drugs known to prolong QTc interval. Do not administer TRISENOX to patients with ventricular arrhythmia or prolonged QTcF.

Contraindications: TRISENOX is contraindicated in patients who are hypersensitive to arsenic.

Differentiation Syndrome: In clinical trials, 16-23% of patients treated with TRISENOX for APL developed differentiation syndrome. Differentiation syndrome has been observed with and without concomitant hyperleukocytosis, and it has occurred as early as day 1 of induction to as late as the second month induction therapy. When TRISENOX is used in combination with tretinoin, prednisone prophylaxis is advised.

Cardiac Conduction Abnormalities: In the clinical trials of patients with newly-diagnosed low-risk APL treated with TRISENOX in combination with tretinoin, 11% experienced QTc prolongation > 450 msec for men and > 460 msec for women throughout the treatment cycles. In the clinical trial of patients with relapsed or refractory APL treated with TRISENOX monotherapy, 40% had at least one ECG tracing with a QTc interval greater than 500 msec. A prolonged QTc was observed between 1 and 5 weeks after start of TRISENOX infusion, and it usually resolved by 8 weeks after TRISENOX infusion. There are no data on the effect of TRISENOX on the QTc interval during the infusion of the drug.

The risk of torsade de pointes is related to the extent of QT prolongation, concomitant administration of QT prolonging drugs, a history of torsade de pointes, pre-existing QT interval prolongation, congestive heart failure, administration of potassium-wasting diuretics, or other conditions that result in hypokalemia or hypomagnesemia. The risk may be increased when TRISENOX is co-administered with medications that can lead to electrolyte abnormalities (such as diuretics or amphotericin B).

Hepatotoxicity: In the clinical trials, 44% of patients with newly-diagnosed low-risk APL treated with TRISENOX in combination with tretinoin experienced elevated aspartate aminotransferase (AST), alkaline phosphatase, and/or serum bilirubin. These abnormalities resolved with temporary discontinuation of TRISENOX and/or tretinoin. During treatment with TRISENOX, monitor liver chemistries at least 2-3 times per week through recovery from toxicities. Withhold treatment with TRISENOX and/or tretinoin if elevations in AST), alkaline phosphatase, and/or serum bilirubin occur to greater than 5 times the upper limit of normal.

Long-term liver abnormalities can occur in APL patients treated with TRISENOX in combination with tretinoin. In a published series, mild liver dysfunction and hepatic steatosis were seen in 15% and 43%, respectively, of patients at a median of 7 years (range 0-14 years) after treatment with arsenic trioxide in combination with tretinoin.

Carcinogenesis: The active ingredient of TRISENOX, arsenic trioxide, is a human carcinogen. Monitor patients for the development of second primary malignancies.

Embryo-Fetal Toxicity: TRISENOX can cause fetal harm when administered to a pregnant woman. One patient who became pregnant while receiving arsenic trioxide had a miscarriage. Conduct pregnancy tests prior to starting treatment and advise pregnant women of the potential risk to a fetus. Advise patients of reproductive potential to use effective contraception during treatment with TRISENOX and after treatment for 6 months in females and 3 months in males. TRISENOX may also impair fertility in males.

Lactation: TRISENOX is excreted in human milk. Because of the potential for serious adverse reactions in the breastfed child, discontinue breastfeeding during treatment with TRISENOX and for two weeks after the final dose.

Patients with Renal Impairment: Exposure of arsenic trioxide may be higher in patients with severe renal impairment. Patients with severe renal impairment (creatinine clearance less than 30 mL/min) should be monitored for toxicity when these patients are treated with TRISENOX, and a dose reduction may be warranted. The use of TRISENOX in patients on dialysis has not been studied.

Patients with Hepatic Impairment: Since limited data are available across all hepatic impairment groups, caution is advised in the use of TRISENOX in patients with hepatic impairment. Monitor patients with severe hepatic impairment (Child-Pugh Class C) who are treated with TRISENOX for toxicity.

Most Common Adverse Reactions: The most common adverse reactions (greater than 30%) were leukocytosis, neutropenia, thrombocytopenia, nausea, vomiting, diarrhea, abdominal pain, hepatic toxicity, fever, rigors, fatigue, insomnia, tachycardia, QTc prolongation, edema, hyperglycemia, hypokalemia, hypomagnesemia, dyspnea, cough, rash or itching, sore throat, arthralgia, headaches, paresthesia, and dizziness.

TO REPORT SIDE EFFECTS: Contact us at 1-888-483-8279 or [email protected]

Indications

TRISENOX is indicated:

In combination with tretinoin for treatment of adults with newly-diagnosed low-risk acute promyelocytic leukemia (APL) whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
For induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

On January 15, 2018 Biotecnol and University of Naples reported a study on Journal of Immunology, Volume 42 Issue 1: pg 1-10,where it was shown that T-cell recruiting bispecific antibody derivatives (TRBA) offer a more effective alternative to standard antibody therapy (Press release, Biotecnol, JAN 15, 2018, View Source [SID1234570281]). The team evaluated a panel of TRBAs targeting 3 different epitopes on the HER2 receptor either in a bivalent targeting tribody structure or as a monovalent scFv-fusion (BiTE format) for binding, cytotoxicity on Trastuzumab-resistant cell lines, and induction of cardiotoxicity. All three TRBAs did bind with high affinity to the HER2 extracellular domain and a large panel of HER2-positive tumour cells. Tribodies had an increased in vitro cytotoxic potency as compared to BiTEs. It was noted that Tribodies targeting the epitopes on ErbB2 receptor domains I and II bind and activate lysis of mammary and gastric tumour cells more efficiently than a Tribody targeting the Trastuzumab epitope on domain IV. The first 2 are also active on Trastuzumab-resistant cancer cells lacking or masking the epitope recognized by Trastuzumab. None of the Tribodies studied showed significant toxicity on human cardiomyocytes. Altogether these results make these novel anti-HER2 bispecific Tribodies candidates for therapeutic development for treating HER2-positive Trastuzumab-resistant cancer patients.

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On January 15, 2018 Ipsen (Euronext: IPN; ADR: IPSEY) reported that irinotecan liposome injection (Onivyde), cabozantinib (Cabometyx), lanreotide (Somatuline Autogel / Depot), and telotristat ethyl (Xermelo) are the subject of 11 posters, along with 2 others focusing on patients living with neuroendocrine tumors, at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Gastrointestinal Cancers Symposium (ASCO-GI), January 18-20, 2018 in San Francisco (CA, USA) (Press release, Ipsen, JAN 15, 2018, View Source [SID1234523186]). In addition, cabozantinib (Cabometyx) will be featured in one oral abstract session:

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Oral Abstract Session B – Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract Friday, January 19: 2:15 PM-3:45 PM

Abstract 207:
Cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC) who have received prior sorafenib: results from the randomized phase 3 CELESTIAL trial.

First Author: Ghassan Abou-Alfa, MD

"Ipsen has a strong presence in oncology at ASCO (Free ASCO Whitepaper)-GI 2018 with 13 posters dealing with clinical outcomes in pancreatic cancer, advanced hepatocellular carcinoma, neuroendocrine tumors and carcinoid syndrome. We and Exelixis, our partner, are excited to announce that the results of the pivotal Phase 3 CELESTIAL Trial of Cabozantinib in Previously Treated Advanced Hepatocellular Carcinoma will be shared for the first time with the medical community as a late breaking presentation, on January 19th," said Alexandre Lebeaut, MD, Executive Vice-President, R&D, Chief Scientific Officer, Ipsen.

2 poster sessions (poster session B and poster session C) with 7 abstracts/posters featuring nal-IRI / liposomal irinotecan (ONIVYDE) :

Poster Session B – Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Poster Display Session, Friday, January 19: 11:30 AM-1:00 PM and 5:30 PM-6:30 PM

BOARD F20 – (Abstract 335)
Deposition characteristics and resulting DNA damage patterns of liposomal irinotecan (nal-IRI) in pancreatic cancer xenografts.

First Author: Shannon Leonard

BOARD H16 – (Abstract 379)
Subgroup analysis by baseline pain intensity (BPI) and analgesic use (BAU) in NAPOLI-1: A phase III study of liposomal irinotecan (nal IRI)±5-fluorouracil/ leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy.

First Author: Teresa Macarulla, MD, PhD

BOARD J2 – (Abstract 388)
Dose modifications of liposomal irinotecan (nal-IRI) + 5-fluorouracil/leucovorin (5-FU/LV) in NAPOLI-1: Impact on efficacy.

First Author: Andrea Wang-Gillam, MD, PhD

BOARD K3 – (Abstract 410)
Subgroup analysis by baseline (BL) weight-associated parameters: A phase III study of liposomal irinotecan (nal IRI)±5 fluorouracil/leucovorin (5 FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based (gem) therapy.

First Author: Teresa Macarulla, MD, PhD

BOARD M6 – (Abstract 459)
Nomogram for predicting overall survival (OS) in patients (pts) treated with liposomal irinotecan (nal-IRI) ± 5-fluorouracil/leucovorin (5-FU/LV) in metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy in NAPOLI-1.
First Author: Andrea Wang-Gillam, MD, PhD

BOARD M7 – (Abstract 460)
Subgroup analysis by measurable metastatic lesion (ML) number and selected lesion locations (LL) at baseline (BL) in NAPOLI 1: A phase III study of liposomal irinotecan (nal-IRI)±5 fluorouracil/leucovorin (5 FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy.
First Author: Jens Siveke, Prof. Dr. med.

Poster Session C – Cancers of the Colon, Rectum, and Anus

Poster Session Display, Saturday, January 20: 7:00 AM-7:55 AM and 11:30 AM-1:00 PM

BOARD G24 – (Abstract 711)
Influence of liposomal irinotecan (nal-IRI) and non-liposomal irinotecan, alone and in combination, on tumor growth and angiogenesis in colorectal cancer (CRC) models.
First Author: Annette Larsen, DVM, PhD

Cabozantinib (Cabometyx) is featured in 2 sessions:

Oral Abstract Session B – Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract Friday, January 19: 2:15 PM-3:45 PM

Abstract 207:
Cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC) who have received prior sorafenib: results from the randomized phase 3 CELESTIAL trial.

First Author: Ghassan Abou-Alfa, MD

Poster Session B – Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Poster Session Display, Friday, January 19: 11:30 AM-1:00 PM and 5:30 PM-6:30 PM

BOARD A4 – (Abstract 207)
Cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC) who have received prior sorafenib: results from the randomized phase 3 CELESTIAL trial.

First Author: Ghassan Abou-Alfa, MD

Lanreotide (Somatuline Autogel / Depot) is featured in 1 poster session:

Poster Session B – Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Poster Session Display, Friday, January 19: 11:30 AM-1:00 PM and 5:30 PM-6:30 PM

BOARD G8 – (Abstract 347)
Lanreotide for the prolonged control of carcinoid syndrome (CS) in somatostatin analog (SSA)-naïve or experienced patients.

First Author: Edward Wolin, MD

Neuroendocrine tumors clinical research is featured in 1 poster session:

Poster Session B – Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Poster Session Display, Friday, January 19: 11:30 AM-1:00 PM and 5:30 PM-6:30 PM

BOARD G20 – (Abstract 359)
Living with neuroendocrine tumors: Assessing quality of life (QoL) through a mobile application.
First Author: Jared Adams, MD, PhD

BOARD E8 – (Abstract 299)
Physical, emotional, and informational challenges of patients living with neuroendocrine tumors in the United States: Understanding their unmet needs.
First Author: Grace Goldstein

Telotristat ethyl (Xermelo) is featured in 1 poster session

Poster Session B – Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Poster session, Friday, January 19: 11:30 AM-1:00 PM and 5:30 PM-6:30 PM

BOARD J9 – (Abstract 395)
Time to sustained improvement in bowel movement frequency with telotristat ethyl: Analysis of the phase III TELECAST study.
First Author: Joseph Dillon

Nota bene: Approved indications for products vary by country and not all indications are available in every country. The product safety and efficacy profiles have not yet been established outside the approved indications.

On January 12, 2018 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that the U.S. Food and Drug Administration (FDA) approved BRACAnalysis CDx for use as a companion diagnostic by healthcare professionals to identify patients with HER2-negative metastatic breast cancer who have a germline BRCA mutation and are candidates for treatment with the PARP inhibitor Lynparza (olaparib), marketed by AstraZeneca and Merck, known as MSD outside of the U.S. and Canada (Press release, Myriad Genetics, JAN 12, 2018, View Source [SID1234523106]). BRACAnalysis CDx is the first and only FDA-approved test for use in this indication.

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"This important advance underscores the need for patients with HER2-negative metastatic breast cancer to know their BRCA status with an FDA approved test to help ensure that they will receive the best available therapy," said Johnathan Lancaster, M.D., Ph.D., chief medical officer of Myriad Genetics. "As shown in the OlympiAD study, Myriad’s BRACAnalysis CDx test was proven to accurately identify those patients who had a germline BRCA mutation and may benefit from Lynparza."

The approval also adds to the body of knowledge about the clinical use and value of companion diagnostics to enable personalized medicine for people with cancer.

"We congratulate AstraZeneca and Merck on obtaining FDA approval of Lynparza for patients with metastatic breast cancer, which is the first approval of a PARP inhibitor outside of ovarian cancer. As the pioneers in identifying likely responders to PARP inhibitors, we are excited to broaden the use of BRACAnalysis CDx as the companion diagnostic for this important new indication," said Mark C. Capone, president and CEO, Myriad Genetics. "We will be actively working with all stakeholders to raise awareness so that patients can be immediately tested to determine if they are likely to benefit from Lynparza."

Approximately one in eight women are diagnosed with breast cancer in the United States, and one-third are diagnosed with or will progress to the metastatic stage of the disease.

"There are more than 155,000 patients with metastatic breast cancer in the United States, and we estimate that 125,000 do not know their BRCA status," said Lancaster. "This new FDA approval of BRACAnalysis CDx for patients with metastatic breast cancer significantly expands the population who can access BRCA testing and potentially benefit from PARP inhibition therapy."

The collaboration with AstraZeneca to develop a novel companion diagnostic test to identify candidates for treatment with olaparib began in 2007. The new metastatic breast cancer indication is the second FDA approval of BRACAnalysis CDx for use in conjunction with Lynparza. In Dec. 2014, Myriad received FDA approval for BRACAnalysis CDx to help identify patients with advanced ovarian cancer who are eligible for fourth-line treatment with olaparib. BRACAnalysis CDx is Myriad’s first FDA-approved companion diagnostic and was the first-ever laboratory developed test approved by the FDA.

About BRACAnalysis CDx

BRACAnalysis CDx is an in vitro diagnostic device intended for the qualitative detection and classification of variants in the protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA. Single nucleotide variants and small insertions and deletions (indels) are identified by polymerase chain reaction (PCR) and Sanger sequencing. Large deletions and duplications in BRCA1 and BRCA2 are detected using multiplex PCR. Results of the test are used as an aid in identifying breast and ovarian cancer patients with deleterious or suspected deleterious germline BRCA variants, who are or may become eligible for treatment with Lynparza (olaparib). Detection of deleterious or suspected deleterious germline BRCA variants by the BRACAnalysis CDx test in ovarian cancer patients is also associated with enhanced progression-free survival (PFS) from Zejula (niraparib)maintenance therapy. This assay is for professional use only and is to be performed only at Myriad Genetic Laboratories, a single laboratory site located at 320 Wakara Way, Salt Lake City, UT 84108. Learn more at: View Source

About Lynparza

Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that exploits tumor DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DNA damage response (DDR) mechanisms in cancer cells. Lynparza is currently approved in the United States for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy and for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Patients are selected for therapy based on Myriad’s FDA-approved companion diagnostic. It is also approved by regulatory health authorities in the EU for use as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

In July 2017, AstraZeneca and Merck announced a global strategic oncology collaboration to jointly co-develop and co-commercialize Lynparza.

On January 12, 2018 AstraZeneca and Merck & Co., Inc., (Merck: known as MSD outside the US and Canada) reported that the US Food and Drug Administration (FDA) has approved Lynparza (olaparib), for use in patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been previously treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting (Press release, AstraZeneca, JAN 12, 2018, View Source [SID1234523071]). Patients with hormone receptor positive (HR+) breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Patients are selected for therapy based on an FDA-approved companion diagnostic from Myriad Genetics.

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Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit, AstraZeneca, said: "This new approval for Lynparza makes it the first and only PARP inhibitor approved in metastatic breast cancer, and the only PARP inhibitor approved beyond ovarian cancer. This is significant for breast cancer patients, as the identification of BRCA status, in addition to hormone receptor and HER2 status, becomes a potentially critical step in the management of their disease."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories said: "This additional approval for Lynparza represents an important advance for women with HER2-negative metastatic breast cancer with a germline BRCA mutation, which is a difficult-to-treat cancer. Moreover, this approval adds further impetus to our important collaboration with AstraZeneca in developing cancer therapies."

The approval was based on data from the randomised, open-label, Phase III OlympiAD trial which investigated Lynparza versus physician’s choice of chemotherapy (capecitabine, eribulin, or vinorelbine). In the trial, Lynparza significantly prolonged progression-free survival (PFS) compared with chemotherapy, and reduced the risk of disease progression or death by 42% (HR 0.58; 95% CI 0.43-0.80; P=0.0009 median 7.0 vs 4.2 months). Patients with measurable disease taking Lynparza (n=167) experienced an objective response rate of 52% (95% CI 44-60), double the response rate for those in the chemotherapy arm (n=66) which was 23% (95% CI 13-35). Additionally, patients experienced a confirmed complete response rate of 7.8% for Lynparza compared to 1.5% for the chemotherapy arm. The data from the OlympiAD trial can be found in the June 2017 issue of the New England Journal of Medicine.

Susan M. Domchek, Executive Director of the Basser Center for BRCA at the Abramson Cancer Center of the University of Pennsylvania, and a national leader on the OlympiAD trials, said: "Patients diagnosed with BRCA-related metastatic breast cancer are often younger than other breast cancer patients, and their disease is often much more aggressive and difficult to treat. While there is currently no cure for metastatic breast cancer, today’s approval offers a new, targeted option that may help to delay disease progression for these patients."

The most common adverse reactions (≥20%) in the OlympiAD trial of patients who received Lynparza were nausea (58%), anaemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhoea (21%), and headache (20%). The percentage of patients who discontinued treatment in the Lynparza arm was 5% compared to the chemotherapy arm which was 8%.

This is the third indication approved for Lynparza in the US, where it has been used to treat nearly 4,000 advanced ovarian cancer patients. Lynparza has the broadest clinical development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to deliver Lynparza as quickly as possible to more patients across multiple settings, including breast, ovarian, prostate and pancreatic cancers.

Sustainable and Ongoing Externalisation Revenue
Under the oncology collaboration with Merck, announced in July 2017, AstraZeneca is potentially eligible for more than $6 billion of future Sustainable and Ongoing Externalisation Revenue in the form of sales-related and approval-related payments in addition to option payments until 2019. Following this new approval for Lynparza, AstraZeneca will receive $70 million in Sustainable and Ongoing Externalisation Revenue.

About OlympiAD
OlympiAD is 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 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 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. Hormone receptor-positive 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 Metastatic Breast Cancer (MBC)
Three main receptors drive tumour growth in breast cancer: progesterone receptors (PR), estrogen receptors (ER) and HER2 receptors. A patient’s breast cancer will test either negative or positive for these three receptors. If a tumour tests positive for PR and/or ER, it is considered HR+. If a tumour tests negative for all three receptors, it is considered triple negative.

MBC is the most advanced stage of breast cancer (Stage IV), and occurs when cancer cells have spread beyond the initial tumour site to other parts of the body outside of the breast.

Despite the increase in treatment options during the past three decades, there is currently no cure for patients diagnosed with MBC and only 26.9% of patients survive five years after diagnosis. Thus, the primary aim of treatment is to slow progression of the disease for as long as possible, improving, or at least maintaining, a patient’s quality of life.

It is estimated that in 2018, there will be approximately 155,000 women in the US living with MBC, and this number is projected to increase to approximately 160,000 by the year 2020.

About Germline BRCA Mutations
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role 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 Lynparza (olaparib)
Lynparza is the first FDA-approved oral poly ADP-ribose polymerase (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 investigated in a range of DDR-deficient tumour types and is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DDR mechanisms in cancer cells.

About the AstraZeneca and MSD Strategic Oncology Collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. The collaboration is based on increasing evidence that PARP and MEK inhibitors can be combined with PD-L1/PD-1 inhibitors for a range of tumour types. Working together, the companies will develop Lynparza and selumetinib in combination with other potential new medicines and as a monotherapy. Independently, the companies will develop Lynparza and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.