On July 18, 2016 AstraZeneca reported that the Phase III trial met its primary endpoint, demonstrating superior progression-free survival (PFS) compared to standard platinum-based doublet chemotherapy (Press release, AstraZeneca, JUL 18, 2016, View Source [SID:1234513924]). The AURA3 randomised trial assessed the efficacy and safety of Tagrisso as a 2nd-line treatment in more than 400 patients with EGFR T790M mutation-positive, locally-advanced or metastatic NSCLC, whose disease had progressed following 1st-line EGFR tyrosine kinase inhibitor (TKI) therapy. Tagrisso also demonstrated a safety profile consistent with previous trials.

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In addition to PFS, the objective response rate (ORR), disease control rate (DCR) and duration of response (DoR) also achieved clinically meaningful improvement versus chemotherapy. A full evaluation of AURA3 data, including an analysis of overall survival (OS), is ongoing, and results will be presented at an upcoming medical meeting.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "These results confirm Tagrisso as a meaningful alternative to benefit EGFR T790M lung cancer patients. The AURA3 results demonstrate the benefits of our science-led approach that enabled the rapid development of Tagrisso as a targeted treatment to address the most common cause of resistance to a first-generation EGFR-TKI for patients with metastatic EGFR-mutant lung cancer. We remain committed to exploring the potential of Tagrisso to further extend its reach and help meet patient need."

Tagrisso is one of the fastest development programmes ever, from start of clinical trials to approval in just over two and a half years. It was approved in the US, EU, Japan, Canada, Switzerland, Israel and Mexico as the first treatment for patients with EGFR T790M mutation-positive advanced NSCLC. Tagrisso is also approved in South Korea in the same indication. Eligibility for treatment with Tagrisso is dependent on confirmation that the EGFR T790M mutation is present in the tumour.

AstraZeneca is committed to exploring the full potential of Tagrisso as monotherapy and in combination, for patients with lung cancer, including in adjuvant and locally-advanced/ metastatic 1st-line EGFRm settings. In addition, AstraZeneca is exploring Tagrisso in NSCLC patients with and without brain metastases, and has presented encouraging data in a small cohort of patients with leptomeningeal disease.

About Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths and more than breast, prostate and colorectal cancers combined. Patients who have the EGFRm form of NSCLC, which occurs in 10-15% of NSCLC patients in the US and Europe and 30-40% of NSCLC patients in Asia, are particularly sensitive to treatment with currently-available EGFR-TKIs, which block the cell signalling pathways that drive the growth of tumour cells. However, tumours almost always develop resistance to treatment, leading to disease progression. In approximately two-thirds of patients treated with approved EGFR-TKIs such as gefitinib and erlotinib, this resistance is caused by the secondary mutation, T790M.

About Tagrisso

Tagrisso (osimertinib, AZD9291) 80mg once-daily tablet is the first medicine indicated for the treatment of adult patients with locally-advanced or metastatic EGFR T790M mutation-positive NSCLC. Tagrisso is as an irreversible EGFR inhibitor, born out of scientific exploration and engineered to combat the mechanism of resistance by targeting the T790M resistance mutation.

Tagrisso is also being investigated in the adjuvant and metastatic 1st-line settings, including in patients with and without brain metastases, in leptomeningeal disease, and in combination with other treatments.

About AURA3

AURA3 compared the efficacy and safety of Tagrisso 80mg once daily and platinum-based doublet chemotherapy in 419 patients with EGFR T790M mutation-positive, locally-advanced or metastatic NSCLC whose disease had progressed on or after treatment with a previous EGFR-TKI. The trial was carried out in more than 130 locations worldwide, including the USA, Canada, Europe, China, Japan, Korea, Taiwan and Australia.

The primary endpoint of the trial was PFS, and secondary endpoints included OS, ORR, DoR, DCR, safety and measures of health-related quality of life (HRQoL).

On July 15, 2016 Celgene International Sàrl, a wholly owned subsidiary of Celgene Corporation (NASDAQ: CELG) reported that the European Commission (EC) has approved REVLIMID (lenalidomide) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) (Press release, Celgene, JUL 15, 2016, View Source [SID:1234513887]).

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MCL is a rare sub-type of aggressive non-Hodgkin’s lymphoma (NHL), which starts in the lymph nodes but can move to other organs, causing tumours known as lymphomas. Between 3 and 6 percent of NHL patients have MCL. MCL has the poorest long-term survival of all B-cell lymphoma subtypes, with fewer than 50 percent of patients surviving at 5 years1. In Europe there were 93,433 new cases of non-Hodgkin lymphoma, and 37,900 deaths in 20122. MCL has a median age of onset of 70 years and affects men more often than women3.

"New treatment options are vitally needed in order to change the course of MCL for patients, given the severity of the disease, and there are still limited existing treatment options," said Prof. Marek Trneny, Charles University in Prague. "Lenalidomide is a proven medicine that has shown efficacy in relapsed/refractory MCL, with the MCL-002 study meeting its primary endpoint of an improvement in progression-free survival (PFS)."

Tuomo Pätsi, President of Celgene in Europe, Middle East and Africa (EMEA), adds: "Today is an important milestone in the fight to find new treatment options for patients with MCL, a difficult-to-treat disease with a high unmet medical need. The approval by the European Commission for REVLIMID in relapsed/refractory MCL gives us the opportunity to support patients in their fight against this disease, with an innovative treatment, and it is only the beginning of our work to support the needs of patients with MCL. We have a robust clinical program of lymphoma studies reaching patients across the globe with an aim to find new treatment options across numerous types of lymphoma."

The EC decision was based on data from MCL-002, a phase II, multicenter, randomized open-label study to determine the efficacy and safety of REVLIMID versus the investigator’s choice (IC), in 254 patients who were refractory to their last treatment or had relapsed one to three times. In the study, REVLIMID showed a significant improvement in progression-free survival (PFS) of 8.7 months vs. 5.2 in the control arm (HR = 0.61, p value of .004)4.

In the study, the most frequently observed adverse reactions which occurred more frequently in the REVLIMID arm compared with the IC arm were neutropenia (50.9%), anaemia (28.7%), diarrhoea (22.8%), fatigue (21.0%), constipation (17.4%), pyrexia (16.8%), and rash (16.2%).

The EC decision for the use of REVLIMID in adult patients with relapsed/refractory MCL follows the positive opinion issued by the Committee for Medicinal Products for Human Use (CHMP) earlier this year. The EC decision marks the 6th new product or indication granted to Celgene in the last 18 months in the European Union. In 2015, Celgene announced the EC approval of medicines for newly diagnosed multiple myeloma, another form of blood cancer; psoriasis and psoriatic arthritis; a specific subset of acute myeloid leukaemia (AML) patients; and non-small-cell lung cancer (NSCLC).

In addition to the EU approval, REVLIMID is indicated for the treatment of patients with relapsed/refractory MCL in the United States, Switzerland, Israel, Turkey, Australia, and numerous countries in Latin America. REVLIMID is also indicated in various countries including the EU for treatment of newly diagnosed and relapsed/refractory multiple myeloma and myelodysplastic syndromes.

IMPORTANT SAFETY INFORMATION

WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

Do not use REVLIMID during pregnancy. Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study. Thalidomide is a known human teratogen that causes severe life-threatening human birth defects. If lenalidomide is used during pregnancy, it may cause birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting REVLIMID treatment. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treatment.

Hematologic Toxicity (Neutropenia and Thrombocytopenia)

REVLIMID can cause significant neutropenia and thrombocytopenia. Eighty percent of patients with del 5q MDS had to have a dose delay/reduction during the major study. 34% of patients had to have a second dose delay/reduction. Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled in the study. Patients on therapy for del 5q MDS should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or reduction. Patients may require use of blood product support and/or growth factors.

Venous and Arterial Thromboembolism

REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as risk of myocardial infarction and stroke in patients with MM who were treated with REVLIMID and dexamethasone therapy. Monitor for and advise patients about signs and symptoms of thromboembolism. Advise patients to seek immediate medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. Thromboprophylaxis is recommended and the choice of regimen should be based on an assessment of the patient’s underlying risks.

About REVLIMID

REVLIMID is approved in Europe for the treatment of adult patients with previously untreated multiple myeloma (MM) who are not eligible for transplant. REVLIMID is also approved in combination with dexamethasone for the treatment of patients with MM who have received at least one prior therapy in nearly 70 countries, encompassing Europe, the Americas, the Middle-East and Asia, and in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy in Australia and New Zealand.

REVLIMID is also approved in the United States, Canada, Switzerland, Australia, New Zealand and several Latin American countries, as well as Malaysia and Israel, for transfusion-dependent anaemia due to low- or intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities and in Europe for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.

In addition, REVLIMID is approved in the United States for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. In Switzerland, REVLIMID is indicated for the treatment of patients with relapsed or refractory MCL after prior therapy that included bortezomib and chemotherapy/rituximab.