Lung cancer management is about to undergo a paradigm shift where patients will get cancer therapy tailored to their tumour’s molecular profile, experts told journalists last week during a European Society for Medical Oncology (ESMO) international chest tumour symposium in Geneva.

New diagnostics to detect specific biomarkers will be able to predict which non-small cell lung cancer (NSCLC) patients will respond best to targeted therapies giving them a greatly enhanced chance of longer survival. There is already a parallel in breast cancer where detection of HER 2 positivity identifies patients who will respond to breast cancer treatment with Roche's Herceptin (trastuzumab).

In NSCLC, detection of a specific biomarker could soon identify candidates most likely to respond to targeted therapy with the Swiss firm's Tarceva (erlotinib). A greater than 80% chance of response and at least one-year survival is predicted for patients with the right profile.

Developments will start to unfold later this year as data from two groundbreaking studies, start to become available. Roche hopes that these will reveal the benefits of targeting patients with specific biomarkers in NSCLC with Tarceva.

New prospective trial data on biomarkers will be presented at this year’s ASCO in June and at the World Congress on Lung Cancer to be held in Seoul in September. Speaking in Geneva Dr Luiz Paz-Ares Rodriguez of the 12 October University Hospital, Madrid, Spain said the Phase II MERIT study of 250 patients will define the value of biomarkers identified by different strategies including immunohistochemistry, FISH (fluorescent in situ hybridisation) and gene analysis for presence of specific mutations. Next year will see the results of the phase III placebo-controlled SATURN trial described by Roche as “the most important randomised and adequately powered Phase III trial to answer the question of whether or not patients can be selected on the basis of biomarkers.” The study involving 152 centres has randomised patients to treatments according to their biomarker profile.

Earlier data from Spanish studies strongly suggest that patients with two specific epidermal growth factor receptor (EGFR) gene mutations located on the kinase domain of EXON 19 and 21 respond particularly well to Tarceva, said Dr Paz-Ares Rodriguez. According to retrospective analyses, patients with the mutation show a much higher response rate to Tarceva compared to those without – up to 80% compared to 10% overall. A small prospective study where lung cancer patients were treated with Tarceva only if they had the gene mutation showed a response rate of 82% and a one-year survival rate also of 82%.

Presence of the mutation varies among different races and type of NSCLC, he said. Among Asian people (excluding the Indian subcontinent) the mutation is present in around 25% of lung cancers whilst among western Europeans the prevalence is between 10% and 15%. It is also more likely to be found in the lung adenocarcinomas affecting non-smokers, a condition rising among women in the 30 to 50 age group. However, Tarceva also benefits male patients with lung cancers caused by tobacco, stressed Professor Nick Thatcher, a lung cancer specialist at the Christie Hospital and University of Manchester.

New assays in development

According to Roche’s International Product Manager George Gauthier, Roche is working with tissue diagnostics companies to develop tests for biomarkers which can currently be identified only by a few specialised laboratories . “Our goal is to try to have commercially available validated assays on the market at the same time the SATURN data become available” he disclosed. “If the data indicate that patients with a specific biomarker do well, clinicians will need to have a test for that biomarker which is easily accessible. Hopefully, within the next four years patients will have ready access to tests to help them assess their best treatment options,” he predicted.

The discovery of biomarkers could pave the way for wider uptake of targeted therapies throughout Europe and drugmakers see it as an opportunity of getting some of their more expensive medicines onto the market for targeted populations. Currently, only 14% of European lung cancer patients are benefiting from newer treatments. Research shows access is patchy. Dr Jesme Fox of the Global Lung Cancer Coalition said patients across Europe report difficulty in accessing new cancer drugs. While Tarceva is available in some countries such as Scotland, France, Spain, Austria and Switzerland, access is difficult or non-existent in other countries such as England, Poland, Norway, and the Czech Republic.

When Tarceva was originally turned down for recommended use by England’s National Health Service patients on cost grounds by the UK’s National Institute for Health and Clinical Effectiveness, chief executive Andrew Dillon recommended that further research be undertaken into subgroups for whom the drug may provide greater benefit. The NICE guidance on Tarceva should be considered for early review in February 2008, he added. Restricting treatment to the patients most likely to respond could encourage wider approval of reimbursement in other countries also. By Olwen Glynn Owen