AstraZeneca's Potential $3 Billion Cancer Pill Wins Early Approval

“A new lung cancer pill from AstraZeneca, designed for patients whose disease has worsened after treatment with other therapies, won early U.S. approval on Friday, in a boost for the British drugmaker.

“Tagrisso, also known as AZD9291, is one of several cancer medicines AstraZeneca hopes will rebuild its sales following patent losses on older drugs. During its defense against a takeover attempt by Pfizer last year, the firm forecast the drug could eventually sell as much as $3 billion a year.

“Industry analysts are more cautious about sales in the next few years, with consensus expectations pointing to revenue of $1.1 billion in 2020, according to Thomson Reuters Cortellis.”


AZD9291 Shows Clinical Activity in Non-Small Cell Lung Cancer Patients with Leptomeningeal Disease

“The epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) AZD9291 crossed the blood-brain barrier and showed clinical activity in heavily pretreated non-small cell lung cancer (NSCLC) patients with leptomeningeal disease, a disease in which lung cancer cells spread to the membranes surrounding the brain and spinal cord, according to data from a phase I BLOOM clinical trial presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Nov. 5–9.

” ‘Leptomeningeal disease at initial diagnosis of NSCLC is rare; however, as their lung cancer progresses, up to 15 percent of patients will develop this devastating complication. Additionally, an increased risk of central nervous system [CNS] involvement has been reported among patients with EGFR-mutant NSCLC, in particular those treated with a first-generation EGFR-TKI,’ said Dae Ho Lee, MD, PhD, associate professor in the Department of Oncology in the University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.”


High Response Rate Produced by Osimertinib in EGFR T790M-Mutant NSCLC

“Osimertinib (AZD9291), the third-generation TKI, demonstrated a 71% objective response rate (ORR) in those with EGFR T790M-mutant non-small cell lung cancer (NSCLC), following resistance to frontline anti-EGFR therapy, according the findings of the phase II AURA2 trial that was presented at this year’s World Conference on Lung Cancer (WCLC).

“The ORR consisted of 2 complete responses and 139 partial responses. The stable disease rate at ≥6 weeks was 21%, for a disease control rate of 92%. After a median follow-up of 6.7 months, the median progression-free survival (PFS) was 8.6 months. The median duration of response was 7.8 months (27% maturity).”


AstraZeneca Presents Further Evidence for the Potential of AZD9291 in First-Line and Pre-Treated Non-Small Cell Lung Cancer

“AstraZeneca today announced updated data on AZD9291 in first-line patients with epidermal growth factor receptor mutation (EGFRm) positive advanced non-small cell lung cancer (NSCLC) and previously-treated patients with EGFRm T790M mutation-positive NSCLC. The data being presented today at the World Conference on Lung Cancer (WCLC) 2015 were from the AURA Phase I trial first-line cohort and two AURA Phase II studies.

“Data demonstrated that in 60 patients who received AZD9291 once daily in the first-line setting, 72% (95% confidence interval (CI) 58% to 82%) were progression free (PFS) at 12 months. Confirmed overall response rate (ORR) was 75% (95% CI 62% to 85%). The longest duration of response (DoR) was ongoing at 18 months.

“ ‘While the data are still preliminary, these latest results from the AURA trial first-line cohort further reinforce the potential of AZD9291 in treatment-naïve EGFRm advanced NSCLC patients,’ said Professor Suresh S. Ramalingam, presenting author of the AURA trial first-line cohort data and Chief of Thoracic Oncology and Director of Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.”


AstraZeneca Presents Positive Data on AZD9291 in First-Line EGFR Mutated Lung Cancer at ASCO 2015

“AstraZeneca today announced preliminary efficacy and safety data for AZD9291 in the first-line treatment of epidermal growth factor receptor mutation positive (EGFRm) advanced non-small cell lung cancer (NSCLC). Data showed that 81% (95% confidence interval (CI) 68% to 89%) of patients on a once daily dose of AZD9291 were progression free at 9 months; overall response rate was 73% (95% CI 60% to 84%). The longest duration of response was ongoing at 13.8 months at the time of data cutoff.1

“The data from the first-line expansion cohorts of the AURA Phase I study were presented at the annual meeting of the American Society of Clinical Oncology in Chicago. The first-line cohorts included 60 patients with EGFRm advanced NSCLC who received AZD9291 80mg or 160mg once daily. The data are not fully mature with an approximate 11 month median follow up in the 80mg cohort, and an approximate 8.5 month median follow up in the 160mg cohort. The most common adverse events in both cohorts included rash (grade 3:0% at 80mg)(grade 3:3% at 160mg) and diarrhea (grade 3:0% at 80mg)(grade 3:7% at 160mg).1

“ ‘These preliminary data demonstrate the potential of AZD9291 in treatment-naive advanced NSCLC patients with EGFR mutation. These promising results with AZD9291 will be studied further by the ongoing Phase III FLAURA trial2 in the first-line setting,’ said Professor Suresh S. Ramalingam, Chief of Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA, who presented the AURA first-line data and is lead principal investigator for the FLAURA study.”


AZD9291 Shows Durable Responses in Patients With EGFR-Positive Lung Cancers

“A clinical trial of the EGFR inhibitor AZD9291 in patients with advanced non–small cell lung cancer (NSCLC) who had disease progression after previous treatment with EGFR tyrosine kinase inhibitors has found that the drug was highly active—achieving a 95% disease control rate—in patients with the EGFR T790M mutation. The median progression-free survival was 9.6 months in the EGFR T790M–positive patients, and 2.8 months in EGFR–negative patients. Why the drug is less effective in patients whose cancers lacked the T790M mutation is unclear. The study by Jänne et al is published in The New England Journal of Medicine.

“A total of 253 patients were enrolled in the study. The researchers administered AZD9291 at doses of 20 mg to 240 mg once daily in patients with advanced lung cancer who had radiologically documented disease progression after previous treatment with EGFR tyrosine kinase inhibitors.

“The study included dose-escalation cohorts and dose-expansion cohorts; prestudy tumor biopsies were required for central determination of EGFR T790M status in the expansion cohorts. Patients were assessed for safety, pharmacokinetics, and efficacy.”


Two New Drugs for EGFR+ Lung Cancer That Has Progressed

“Two new drugs for a specific lung cancer scenario are approaching the market –― AZD9291 (AstraZeneca Pharmaceuticals LP) and rociletinib (Clovis Oncology), and both companies are preparing to file for approval.

“Both drugs are third-generation EGFR inhibitors destined for use in patients who have non–small cell lung cancer (NSCLC) that is EGFR-mutation-positive and has responded to treatment with first-line EGFR inhibitors, but is now progressing.

“In about 60% of these cases, the disease is progressing because the tumor has developed a new mutation, known as EGFR T790M. This mutation confers resistance to treatment with first- generation EGFR inhibitors, such as erlotinib (Tarceva, Osi Pharmaceuticals, Inc) and gefitinib (Iressa, AstraZeneca Pharmaceuticals LP) or the second-generation EGFR inhibitor afatinib (Gilotrif, Boehringer Ingelheim Pharmaceuticals, Inc).”


AZD9291 Delays Progression of EGFR-Mutant Lung Cancers by 1 Year

“An experimental lung cancer pill from AstraZeneca delays disease progression by more than a year, according to new data presented at a medical meeting on Friday.

“AZD9291, which the company expects to file for U.S. approval in the second quarter of 2015, is one of a number of cancer medicines AstraZeneca is hoping will rebuild its sales following patent losses on older drugs.

“An analysis presented at the European Lung Cancer Conference in Geneva demonstrated a median progression-free survival for patients on the drug of 13.5 months.”


Lung Cancer Pioneer Thomas Lynch Discusses the State of the Art

“Thomas Lynch, MD, has been a leader in the development of numerous novel therapies for the treatment of lung cancer. His significant contributions to the field have earned him great recognition, including the 2013 Giants of Cancer CareTM award in Lung Cancer for his pioneering use of molecular testing for EGFR mutations.

“Lynch, who is director of the Yale Cancer Center and physician-in-chief at the Smilow Cancer Hospital at Yale-New Haven, recently sat down with OncLive and discussed key strategies and trends in the management of lung cancer. In a wide-ranging interview, Lynch provides expert insight across the spectrum of care, from screening to the challenges associated with resistance mutations.”