Drug combination gives ‘exciting’ results in ovarian and lung cancer

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Combining a new targeted cancer drug with chemotherapy has shown promise in an early clinical trial, in patients with ovarian or lung cancer for whom all other treatments had failed.

The combination of targeted drug vistusertib along with paclitaxel chemotherapy caused tumours of over half of patients with ovarian cancer and over a third with lung cancer to shrink, and stopped patients’ tumours from growing for nearly six months.

The study, led by a team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, was so successful that a phase II trial began while the phase I trial was still recruiting.

The study is published in Annals of Oncology and was funded by AstraZeneca, with support from the NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research (ICR) and the Experimental Cancer Medicine Centre (ECMC) and part of the Combinations Alliance portfolio.

“It’s wonderful that the study has given many of the women and men enrolled in the trial many months extra to spend with their loved ones”

The researchers at the ICR and The Royal Marsden, along with teams at nine other centres across the UK, tested the combination on 25 women with high-grade, serous ovarian cancer and 40 patients with squamous non-small cell lung cancer.

All the patients in the study had advanced tumours that had spread round their body, and in each case standard treatment had failed. As this was an early trial, the researchers initially tested if the drug combination was safe, and found it was well tolerated with manageable side-effects.

But the study also looked at the effectiveness of the combination – and found that 52% of the ovarian cancer patients and 35% of the lung cancer patients had a reduction of at least 30% in the size of their tumours.

For each of these cancer types – which had become resistant to all other types of available treatment, including chemotherapy – the combination stopped tumours growing for an average of 5.8 months.

The idea for this drug combination came about after a previous study led by ICR researchers who painstakingly isolated ovarian cancer cells from fluid in the abdomen and found that chemotherapy-resistant ovarian cancers typically have high levels of molecule a called p-S6K. This helps tumours grow quickly – and the researchers believe this may help the disease resist the effects of chemotherapy.

Vistusertib works by targeting proteins called mTOR1 and 2 which ‘turn on’ p-S6K. By combining vistusertib with paclitaxel chemotherapy, the cancer cells can’t use p-S6K to grow and resist chemotherapy, so tumours shrank in many of the patients, the researchers believe.

Although ovarian cancer is sensitive to platinum-based chemotherapies, most patients eventually become resistant to them. There is an urgent need to find new ways to treat patients with platinum-resistant ovarian cancer.

Study leader Professor Udai Banerji, Deputy Director of the Drug Development Unit at the ICR, and The Royal Marsden NHS Foundation Trust, said: “We combined chemotherapy with a targeted drug which blocks the way cancer cells react to treatment in order to survive. What we saw was very exciting. Over half the women with ovarian cancer and over a third of lung cancer patients saw their tumours shrink – and these are patients who had exhausted all other options. The phase II clinical trial of this drug is going well and I very much look forward to seeing the initial results, coming out later this year.

Professor Paul Workman, Chief Executive of the ICR, said: “Drug combinations hold huge promise for tackling cancer’s adaptation, evolution and drug resistance, just as they have in other areas of medicine such as HIV. But it is essential that we choose which drug combinations to test out in trials rationally based on our scientific understanding of what will work. This study is a perfect example of a rational drug combination, selected because of scientific observations made here at the ICR that resistant ovarian cancer cells seemed to rely on a particular protein for their survival after chemotherapy. It’s wonderful that the study has given many of the women and men enrolled in the trial many months extra to spend with their loved ones, where previously they had run out of all treatment options. I eagerly await the results from larger trials of this drug combination.”