Vistusertib Plus Paclitaxel – Promising Results In Ovarian Cancer

Administering 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 vistusertib along with paclitaxel (Taxol) chemotherapy caused tumours of over half of patients with ovarian cancer and over a third with lung cancer to shrink, and stopped patients’ cancers from growing for nearly six months.

The result far exceeds what is expected with standard treatments in patients with advanced disease who have already had, and have now become resistant to, standard treatment. In fact, 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.

Ovarian Cancer Cells

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 cancers that had spread round their body, and in each case standard treatment had failed. Because this was an early phase clinical 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 per cent of the ovarian cancer patients and 35 per cent of the lung cancer patients had a reduction of at least 30 per cent 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 cancers growing for an average of 5.8 months (progression free survival).

Vistusertib

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 cancer cells grow quickly – and the researchers believe this may help cancer 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.

Chemotherapy With A Targeted Drug

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. We collaborated with multiple ECMC sites and delivered the study in record time so it could seamlessly move into a randomised phase II study. This is a testament to all the high-quality research infrastructure in our ECMC and NIHR centres along with the commitment and altruism of patients in the UK.”

Effective treatment options for women with relapsed ovarian cancer are limited, so these results are very encouraging, said Dr Susana Banerjee, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Team Leader in Gynaecological Cancers at the ICR, who is leading the phase II trial.

The research 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.

B Basu, M G Krebs, R Sundar, R H Wilson, J Spicer, R Jones, M Brada, D C Talbot, N Steele, A H Ingles Garces, W Brugger, E A Harrington, J Evans, E Hall, H Tovey, F M de Oliveira, S Carreira, K Swales, R Ruddle, F I Raynaud, B Purchase, J C Dawes, M Parmar, A J Turner, N Tunariu, S Banerjee, J S de Bono, U Banerji
Vistusertib (dual m-TORC1/2 inhibitor) in combination with paclitaxel in patients with high-grade serous ovarian and squamous non-small-cell lung cancer
Annals of Oncology, mdy245, https://doi.org/10.1093/annonc/mdy245

Image: Wellcome Images