Roche immunotherapy drug may be "game changer" in lung cancer


* Engineered antibody drug helps immune system fight cancer

* Early trials promising for lung cancer in smokers

* Lung tumours normally notoriously difficult to treat

By Kate Kelland

AMSTERDAM, Sept 29 (Reuters) - An experimental Roche drug that seems to work particularly well against lungcancer in smokers may be a "game changer" for these normallydifficult-to-treat patients, researchers said on Sunday.

Presenting detailed data from an early-stage trial of thedrug, called MPDL3280A, in patients with a form of the diseasecalled non-small cell lung cancer (NSCLC), investigators saidwhat they had found was "great news for lung cancer patients".

Of 53 patients with NSCLC tumours treated with the drug, 23percent saw their tumours shrink, according to results presentedat the European Cancer Congress (ECC) in Amsterdam.

But the most encouraging numbers were among smokers, wherethe response rate was 26 percent compared with 10 percent ofpatients who had never smoked, said Professor Jean-Charles Soriaof France's Institut Gustave Roussy, who led the study.

Lung cancer, which is usually caused by smoking, isextremely difficult to treat successfully and once it hasstarted to spread to other parts of the body, it is incurable.

Roche's MPDL3280A is an engineered antibody that targets aprotein called PD-L1 - a defence mechanism that tumours use totrick the immune system's T-cells into being inactive.

By blocking PD-L1, the drug allows the T-cells to wake upand recognise the cancer, and then grow and multiply to attackit more efficiently.

Rival drugmakers including Merck and Bristol-MyersSquibb are developing immunotherapy drugs in a similarclass of drugs known as PD-1 inhibitors, also designed tomobilise the body's own immune system to fight cancer.

Soria's team suspected that because lung tumours in smokershave a higher rate of genetic mutations than tumours of lungcancer patients who have never smoked, their immune systems maybe more likely to respond vigorously when PD-L1 is blocked.

So they drilled down into the data more closely, separatingout the 81 percent of the 53 patients who were smokers or formersmokers, and the 19 percent of them who were not.

"And bingo, this is the first targeted agent (drug) thatshows more activity in smokers than in non-smokers," Soria toldreporters in a briefing at the ECC.

Cora Sternberg, co-chair of the ECC's scientific committeeand an oncologist at the San Camillo and Forlanini hospitals inRome who was not involved in the study, said that although theresults were from very early-stage trials, they suggested thedrug was "definitely a game changer" in lung cancer.

Roche is also investigating MPDL3280A's potential fortreating a range of other cancers, including melanoma skincancer and kidney cancer, where it has already shown somepromise in early trials.

Cornelis van de Velde, an oncologist at Leiden UniversityMedical Centre in the Netherlands and president of the EuropeanCancer Organisation, said Soria's was an extremely importantstudy for NSCLC patients, who currently have very few treatmentoptions that make much impact on their disease.

"Hundreds of millions of euros have been spent chasing thedream of immunotherapy for lung cancer patients, but with zeroresults." he said. "These early findings..suggest that it hasthe potential to open new therapeutic approaches."


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