'25 at 25': Defining treatment for ovarian cancer
08 Oct 2024
In this article in our series celebrating 25 years of smarter studies, global impact and better health, we look at how the MRC CTU at UCL has helped define treatment for ovarian cancer.
Ovarian cancer is the 6th most common cancer in females in the UK, with around 7,500 new cases and more than 4000 deaths every year. 1 in 56 UK females will be diagnosed with ovarian cancer in their lifetime.
Over the last 50 years, ovarian cancer survival has almost doubled in the UK. Clinical trials have played an important role in improving treatment options, including some run by the MRC CTU at UCL.
The main treatments for ovarian cancer are surgery and chemotherapy. But in recent years, new medicines have been identified which can be used in addition to chemotherapy, and help improve survival.
ICON7
One example of that is bevacizumab (also known as Avastin). Bevacizumab is an anti-angiogenesis drug, which stops the tumour from developing the new blood vessels it needs to grow.
The ICON7 trial looked at adding bevacizumab to standard chemotherapy for women with ovarian cancer. 1,528 women took part in the trial between 2006 and 2013, from hospitals in 11 countries across Europe, Canada, Australia and New Zealand.
The first results from the ICON7 trial were announced in 2010. The results were positive, showing that combining bevacizumab with standard chemotherapy improves progression-free survival (time without disease worsening or coming back). The effect of bevacizumab was most striking after 1 year, when disease progression had occurred in 15% fewer women treated with bevacizumab than without bevacizumab. Overall, women in the trial who received bevacizumab experienced an average of 1.5 months of extra time without the disease worsening.
The final results of ICON7 were announced in 2013. Overall, the results showed that those in the group receiving bevacizumab did not live for longer than those in the group receiving no bevacizumab. However, for those patients with high-risk disease, who were most likely to have early disease progression, the results were positive and showed an improvement in overall survival of 4.8 months in the group who received bevacizumab.
ICON8B
ICON8B followed on from the results of the ICON7 trial, and the ICON8 trial which looked at weekly chemotherapy compared to standard 3-weekly cycles. ICON8 had found no difference between weekly and three-weekly cycles of chemotherapy. ICON8B looked at whether the combination of weekly chemotherapy and bevacizumab could improve outcomes from ovarian cancer.
579 women took part, and they were allocated at random to a treatment group:
- Standard chemotherapy and bevacizumab. Carboplatin and paclitaxel were given once every three weeks together with bevacizumab for up to 6 cycles (chemotherapy phase). Bevacizumab then continued to be given every 3 weeks for up to 42 weeks after enrolment (maintenance phase).
- Weekly chemotherapy and bevacizumab. The chemotherapy drug paclitaxel was given once a week (at a lower dose), while carboplatin and bevacizumab were given every 3 weeks for up to 6 cycles, as in the standard chemotherapy group (chemotherapy phase). Bevacizumab then continued to be given every 3 weeks for up to 42 weeks after enrolment (maintenance phase).
After following up the participants for an average of five years, the results showed that combining bevacizumab with weekly chemotherapy is more effective at preventing ovarian cancer coming back than standard chemotherapy with bevacizumab. On average, it took five and a half months longer for the cancer to come back or worsen in women who had weekly chemotherapy with bevacizumab, compared with women who had standard chemotherapy with bevacizumab.
Preliminary analysis also suggests that women having weekly chemotherapy live about 10 months longer than those receiving the standard chemotherapy. These results were released in 2023.
ICON6
Another trial which looked at adding a new drug, cediranib, to chemotherapy, was the ICON6 trial. Cediranib is a tablet that, like bevacizumab, stops tumours developing the blood vessels they need to keep growing.
The ICON6 trial looked at 456 women with ovarian cancer that had come back after initial treatment. People taking part were divided at random to receive either standard chemotherapy plus a placebo, or standard chemotherapy with cediranib for either the length of chemotherapy, or for 18 months. The trial recruited participants from December 2007 to December 2011.
ICON6 found that taking cediranib daily during chemotherapy and afterwards for a total of up to 18 months increased the length of time before the disease got worse by an average of 2.3 months, from 8.7 to 11.0 months. People who had cediranib during and after chemotherapy lived on average 5 months longer than those who did not, but the evidence was not strong enough to be sure the survival difference is real. Having cediranib only during chemotherapy did not make any significant improvement compared to having chemotherapy plus a placebo.
CHORUS
The international standard of care for women with suspected advanced ovarian cancer is surgery followed by chemotherapy. The CHORUS trial aimed to find out whether having some chemotherapy before surgery (neoadjuvant chemotherapy) was an acceptable alternative to the international standard of care.
552 women who were diagnosed with stage III/IV ovarian cancer took part in the trial, from hospitals across the UK and in New Zealand. They were recruited between 2004-2010.
The trial found that giving some chemotherapy before surgery was non-inferior to (not worse than) the standard treatment in terms both of the numbers of women who survived overall, and the numbers of women who survived without their disease getting worse (progression-free survival). The results hint that women who had neo-adjuvant chemotherapy had slightly better progression free and overall survival.
CHORUS also found that the women who were given some chemotherapy before surgery were less likely have severe side-effects from their chemotherapy and less likely to have complications after their operation. Additionally, they found that the surgery itself was more likely to be able to remove most of the tumour.
Together, these trials have helped improve treatment options for people with ovarian cancer, contributing to an improvement in survival.
Further information