Combination therapy shows promising results for treatment of advanced ovarian and lung cancer

A combination of drugs has offered promising results in an early clinical trial, where it has shrunk tumours in ovarian and lung cancer patients and prevented tumour growth for nearly six months.

The combination included the targeted drug vistusertib and paclitaxel chemotherapy and was studied by researchers from The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust. Twenty-five women with high-grade, serous ovarian cancer and 40 patients with squamous non-small cell lung cancer were included in the study, all of whom had advanced cancers that had spread round their body, and in each case standard treatment had failed.

As an early clinical study, initial test for safety were performed with the researchers finding it to be well-tolerated and having manageable side effects. Then, the researchers looked at the combinations efficacy and found that it caused tumour shrinkage in more than half of the patients with ovarian cancer (52%) and over a third of the patients with lung cancer (35%), which exceeds that expected with standard treatments in patients with advanced disease.

Additionally, it was noted that the combination therapy stopped the tumours from growing for an average of 5.8 months for each of the cancer types studied.

This combination came about after a previous study, also led by ICR researchers, had revealed a high-level of p-S6K molecules — which help cancers to grow quickly and are believed to help cancers resist chemotherapy treatment — was found in chemotherapy-resistant ovarian cancers.

The targeted drug vistusertib works by targeting proteins called mTOR1 and 2, which ‘turn on’ p-S6K molecules. Through combining vistusertib with chemotherapy the researchers were able to prevent the tumours from using p-S6K to grow and resist chemotherapy, which resulted in tumour shrinkage in many patients.

“We combined chemotherapy with a targeted drug which blocks the way cancer cells react to treatment in order to survive,” revealed study leader Professor Udai Banerji, deputy director of the Drug Development Unit at the ICR, and The Royal Marsden NHS Foundation Trust. “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,” added 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. “In the larger Phase II trial we’ve recruited 140 women with relapsed ovarian cancer across the UK to standard chemotherapy (paclitaxel) or paclitaxel in combination with vistusertib. We need to wait for these results, expected later this year, to see how effective this approach is compared to chemotherapy alone.”

“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,” stressed Professor Paul Workman, chief executive of the ICR. “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.”