Lung cancer is a complex disease that can be classified by the types of cells seen under microscope, and also can be described further by mutation—the changes to the cell causing cancer growth . In other words, lung cancer could occur due to the mutation of different kind of genes. Thus far, researchers had identified a few mutations that might be found in lung cancer. These discoveries introduced the era of personalised care for this disease.
In the media workshop held by AstraZeneca at ESMO Asia 2016 Congress, Mohamed Raza Dewji, Senior Global Medical Affairs Leader, EGFR Therapies Team said, one of the challenges of lung cancer is when the patients come to doctors, most of them are already in their advanced stage as the symptoms unfortunately will only show out at later stage of the disease, and leading to late diagnosis. It is vital to access to early diagnosis for appropriate therapeutic intervention, and thus maximising the likelihood of cure. Mr. Mohamed Raza also mentioned that there is an unmet need to move from “one-size-fits-all” model to a more tailored, personalised approach to optimise the treatment for individual patients.
In Asia, mutation of epidermal growth factor receptor (EGFR) is the most common among Non-Small Cell Lung Cancer (NSCLC) patients. The prevalence is more than double than in Caucasians (15%), recorded at about 30-40%, which is likely due to the underlying genetic predisposition.
How does osimertinib overcome 1st line TKI treatment resistance?
Most patients with advanced EGFR mutation NSCLC disease respond well to the 1st-line EGFR tyrosine kinase inhibitor (TKI) therapy. TKI can bind to EGFR and block the signalling. However, tumours on many patients progress even after the therapy. In around 60 percent of cases, the EGFR patients develop a T790M mutation so that TKI can no longer bind and block the EGFR. In the past, these EGFR T790M mutation-positive NSCLC patients will have to receive chemotherapy to prolong their lives. Good news for these patients is, a drug called osimertinib is an alternative to chemotherapy.
Osimertinib indicated for lung cancer
At AstraZeneca media workshop, clinical experts presented positive data from the AURA3 trial, supported osimertinib as a new standard of care for 2nd-line treatment for patients who have progressed following EGFR TKI treatment. The data was first presented at the 17th World Conference on Lung Cancer in December last year.
A total of 419 patients were enrolled in AURA3 comparing the efficacy and safety of osimertinib 80mg once daily and standard platinum-based doublet chemotherapy. These patients have EGFR T790M mutation-positive, locally-advanced or metastatic NSCLC whose disease had progressed on or after treatment with a previous EGFR TKI therapy. They were randomised (2:1) between the treatment with osimertinib (279 patients) and chemotherapy (140 patients). The trial was carried out in more than 130 clinical centres worldwide, including the USA, Canada, Europe, China, Japan, Korea, Taiwan and Australia.
This first randomised Phase III data showed that osimertinib improved progression-free survival (PFS) by 5.7 months compared with chemotherapy. This means that osimertinib is demonstrated to be more effective in extending lives of patients with no progression and fewer side effects reported, compared to the patients receiving chemotherapy.
The trial result is consistent with earlier findings from the AURA Phase II studies (AURA extension and AURA2). (Refer to the AURA3 Clinical Trial Data Infographics)
Evidently, EGFR mutated lung cancer occurs more in the Asia than in other parts of the world. Asian patients significantly contributed to the data of all the three phases of AURA trials, comprising over 60% of the overall patient population. On top of AURA3, a China-specific study, AURA 17, was completed with 171 patients (98% were Asians) and presented by Prof. Wu Yi-Long at WCLC 2016.
Osimertinib was approved in over 40 countries such as US, EU, Japan, South Korea, Australia, Hong Kong and also Singapore. It is currently under review in China, where nearly half of lung cancer patients are thought to have the EGFR mutation. Patients can be treated with osimertinib once the EGFR T790M mutation is confirmed present in the tumour.
Osimertinib is useful for CNS metastases as well?
Lung cancer could be spread to other areas of the body such as central nervous system (CNS). In patients with EGFR mutation-positive NSCLC, up to 44% might develop CNS metastases, i.e. brain metastases and leptomeningeal (LM) disease .
Patients with CNS metastases have shorter life expectancy than those without, as the treatment of CNS metastases is very challenging.
“The confirmatory Phase III data suggest the potential for osimertinib to replace chemotherapy as the standard of care for patients who have progressed following EGFR TKI treatment. As lung cancer is the most common type of cancer to spread to the brain, it is also encouraging to see the activity of osimertinib in patients with CNS metastases whose prognosis is often particularly poor,” said Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at Astra Zeneca.
The treatment with osimertinib is shown useful in the patients with CNS metastases in the AURA3 study. Progression-free survival in patients with CNS metastases at baseline was longer with osimertinib (8.5 months) than with chemotherapy (4.2 months). (Refer to the AURA3 Clinical Trial Data Infographics)
Lung cancer mutation testing
Tissue biopsy is the current gold standard for lung cancer mutation testing. Tumour samples taken from the patients are used to assess the mutation status. Circulating tumour DNA (ctDNA) testing can be used to replace it for those patients who are not eligible for the repeated biopsy.
ctDNA test is a blood test to detect fragmented tumour DNA circulating in the blood. It is particularly useful for patients who are not suitable for tumour biopsy or cytology procedure, especially when the patients are too ill or when the tumour is too small or inaccessible. However, though it is a non-invasive and low-risk test, ctDNA mutation testing is associated with the possibility of getting false negative result. Thus, tumour sampling procedure is advised to be scheduled at the same time when the blood sample is taken for ctDNA testing so that tumour testing can be carried out quickly if negative ctDNA test result is obtained.
- LUNGevity Foundation. Types of Lung Cancer. Available at: https://www.lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer. Accessed 13 January 2017.
- Eichler et al. EGFR mutation status and survival after diagnosis of brain metastasis in non-small cell lung cancer. Neuro-Oncology. 2010;12;1193-1199.
This article is written by APBN editors, Carmen J.W. Loh and Catherine D. Ong,
based on the information and press materials provided by AstraZeneca.