EFFICACY OF IRESSA CONFIRMED IN CAUCASIANS WITH EGFR MUTATION-POSITIVE ADVANCED NON -SMALL-CELL LUNG CANCER

New data presented at the EMCTO congress showed that first-line therapy with gefitinib (IRESSA) in Caucasian patients with EGFR mutation-positive advanced non-small-cell lung cancer, resulted in a response rate of 70% (95% CI 61-78)

Objective Response Rate (ORR) and Progression-Free Survival (PFS) from the phase IV gefitinib (IRESSA) Follow Up Measure (IFUM) ^[i] study has confirmed that gefitinib is an effective treatment for Caucasian patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC). The data was presented at the European Multidisciplinary Conference in Thoracic Oncology (EMCTO) 2013 in Lugano, Switzerland, on May 10^th, 2013.

Results showed that first-line therapy with gefitinib (n=106)resulted in an ORR of 70% (95% CI 61-78). The ORR seen in this EGFR mutation-positive Caucasian population is similar to that seen in the EGFR mutation-positive IPASSⁱⁱ population, therefore gefitinib appears to be consistent in its efficacy in patients with EGFR mutation-positive NSCLC irrespective of whether they are Asian or Caucasian. The secondary efficacy endpoints of disease control rate (DCR; complete/partial response or stable disease ≥6 weeks) was 91% (95% C.I. 84 - 95), estimated median PFS was 9.7 months, and estimated median OS was 19 months. The adverse event profile of gefitinib in this population was consistent with previous clinical experience and prescribing information.

“Gefitinib pioneered targeted therapy for non-small-cell lung cancer patients, and these results confirm that gefitinib is as effective in Caucasian patients with advanced NSCLC with epidermal growth factor receptor mutations, as in other ethnicities”, says Dr Odd Terje Brustugun, Oslo University hospital, Radiumhospitalet, Norway.

IFUM, a Phase IV, open-label, multicentre, single arm study was conducted in 13 countries in Europe, including Norway, to characterise the efficacy, safety and tolerability of gefitinib in Caucasian patients with EGFR mutation-positive advanced NSCLC.

Gefitinib was granted a full Marketing Authorisation Approval in Europe in June 2009 in patients with EGFR mutation-positive advanced NSCLC. This ‘Follow Up Measure’ study was designed to better characterize the profile of gefitinib in the Caucasian patients with EGFR mutation positive advanced NSCLC in the first line setting.

Gefitinib is a single once-daily oral tablet, is an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), which targets and blocks the activity of the EGFR-TK, an

enzyme that regulates intracellular signaling pathways implicated in cancer cell proliferation and survival. Growth factor signaling has been identified as a key driver of tumor growth and spread in a wide range of cancers. Studies have shown that EGFR mutation positive advanced NSCLC is particularly sensitive to gefitinib.^[ii],[iii]

About IFUM

The primary endpoint was the Objective Response Rate (Complete Response or Partial Response) based on investigators assessment in patients treated with gefitinib (IRESSA™ ) using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, in Caucasian patients with EGFR mutation positive (EGFR M+) NSCLC. ORR (95% C.I.) was 70% (61% to 78%).

Sensitivity analysis of the ORR was planned in the protocol to be derived by an independent central review of all scans. ORR (95% CI) was 50% (41% to 59%). Of note, a number of patients were reported as not having measurable disease at baseline by the central reviewers and therefore non-evaluable for tumour response; ORR (95%CI) excluding these patients was 60%(49% - 69%). Since measurable disease was an inclusion criterion for the IFUM study, this supplementary analysis may be considered to represent the likely outcome if the central review had been the primary derivation of ORR.

The majority of patients experienced adverse events (AEs) (93.5%), and reported adverse events were severe (CTC grade 3 or higher) in 15% of patients.  AEs leading to discontinuation of study treatment were reported in 7.5% of patients. Serious Adverse Events were reported in 18.7% of patients, only 2 patients reported an SAE that was considered as potentially related to gefitinib by the investigators. Five SAEs have been reported with an outcome of death, none of them considered potentially related to study treatment by the investigator. The most common adverse events reported were rash (45%) and diarrhoea (31%) and were mainly of mild or moderate severity (CTC grade 1 and 2).  One case of ILD was reported and one case of pneumonitis, neither of those cases was fatal.

About Lung Cancer

More than 3.300 people are diagnosed with lung cancer yearly in Sweden and more than 12.000 are diagnosed in the Nordics. Lung cancer is causing the most cancer deaths in the Nordics – more than 11.000 people die annually due to lung cancer. Non-small-cell lung cancer is the most common type of lung cancer. The other main type is small-cell lung cancer.⁶

Lung cancer has been the most common cancer in the world for several decades and by 2008, there were an estimated 1.61 million new cases. It was also the most common cause of death from cancer, with 1.38 million deaths.^[iv]When lung cancer is detected at early stages, before it has spread to other organs or lymph nodes, around half of patients can survive for five years or more. However, few lung cancers are found at early stage and it is usually diagnosed at the advanced stage, when five year survival falls to approximately 15%.^[v]

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialisation of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com.

Contactpersons

Petra Eurenius, Kommunikationschef AstraZeneca Nordic-Baltic, +46 709 186562

Odd Terje Brustugun, Assoc. prof., MD, Ph.D, Oslo University hospital, Radiumhospitalet,

+47 22 93 40 00, e-mail: odd.terje.brustugun@ous-hf.no

References

[i] Douillard et al. Efficacy, safety and tolerability results from a phase IV, open-label, single arm study of 1st-line gefitinib in Caucasian patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) - EMBARGOED BY ECTMO CONGRESS UNTIL 10th MAY 2013

[ii] Mok TS et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. New Engl J Med 2009; 361: 947-957.

[iii] Sequist LV. et al. First-line gefitinib in patients with advanced non-small cell lung cancer harbouring somatic EGFR mutations. Journal of Clinical Oncology; 26: 2442-2449. 2008.

[iv] Ferlay, J. et al. GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No. 5. version 2.0. Lyon: IARC Press, 2004.

[v] Bepler G.Lung cancer epidemiology and genetics. J Thorac Imaging 1999; 14(4):228-234.

⁶http://www.cancerfonden.se/Global/Dokument/Cancerfonden/Cancerfondsrapporter/Cancerfondsrapporten%202011.pdf