Mini oral session 1

In this video, Prof Dr Hannelore Denys discusses and comments on the data of some exciting studies presented at ESMO 2024 during the Mini Oral session on gynaecological cancer.  

Immunotherapy has historically faced challenges in ovarian cancer, with few notable successes. Researchers are exploring new approaches to improve outcomes, including targeting specific patient populations and utilising combination therapies. One such example is the MoST CIRCUIT trial conducted in Australia and New Zealand, which investigated the combination of nivolumab and ipilimumab in rare tumour types. This trial enrolled 240 patients, including a cohort focused on gynaecological cancers, specifically clear cell tumours. The clear cell cohort comprised 26 patients, 22 of whom had ovarian cancer. The choice of clear cell tumours was deliberate, as they represent a high unmet medical need and share some characteristics with renal clear cell carcinomas, where immunotherapy has shown promise. These tumours tend to have higher PD-L1 expression and greater immune cell infiltration, making them more likely candidates for immunotherapy.

The results were encouraging in this small cohort of clear cell ovarian cancer patients. The overall response rate was 50%, and the median 6-month progression-free survival was 56%. These findings align with the results of the BrUOG 354 trial, presented at ASCO earlier this year, which also tested the combination of nivolumab and ipilimumab in a similar setting. Although this is still a small study, the results provide hope for the potential of immunotherapy in highly selected populations with ovarian cancer.

Another approach to enhancing the effectiveness of immunotherapy in ovarian cancer involves combining immunotherapy with anti-VEGF therapy. VEGF promotes an immune-suppressive tumour microenvironment by activating regulatory T cells  and myeloid-derived suppressor cells, making the tumour more resistant to immune responses. This strategy was employed in the ATALANTE trial, a phase 3 study that focused on patients with platinum-sensitive recurrent ovarian cancer. In the trial, patients received platinum-based chemotherapy plus bevacizumab and were then randomized to either atezolizumab or a placebo. The initial results had already shown that the trial was negative, with no significant improvement in PFS. The addition of atezolizumab only resulted in a 2-month PFS benefit, which was not statistically significant. However, at the recent ESMO meeting, the 5-year exploratory overall survival data was presented. This new data showed a 5-month OS benefit with the addition of atezolizumab, with a median OS of 35 months compared to 30 months in the control arm. Moreover, the likelihood of being alive at 5 years was higher in the atezolizumab arm (27%) compared to the control arm (17%). While these results suggest that a subset of patients might benefit from atezolizumab, the overall trial was still negative. The challenge remains to identify which patients are most likely to benefit, and further translational research is needed to pinpoint those individuals who respond better to this combination therapy.

The INTERLACE trial is one of two recent positive trials in the treatment of locally advanced cervical cancer, the other being the KEYNOTE trial. INTERLACE involved 500 patients who were randomised to receive either six weeks of induction chemotherapy (carboplatin-paclitaxel) followed by standard chemoradiation or chemoradiation alone. The trial showed a significant survival benefit for patients who received the induction chemotherapy.

At the 5-year mark, OS was 80% in the induction chemotherapy arm compared to 72% in the chemoradiation-only arm, indicating a clear advantage to the addition of chemotherapy before radiation. At ESMO 2024, quality of life data from the trial was presented, showing no sustained negative impact from the induction chemotherapy on patients’ quality of life. This is reassuring, as it supports the clinical benefit of this treatment approach.

The ICON9 trial investigated the combination of the PARP inhibitor olaparib with the anti-VEGF agent cediranib in patients with platinum-sensitive ovarian cancer. Participants received platinum-based chemotherapy and were then randomised to either olaparib alone or olaparib plus cediranib. Unfortunately, the trial was negative, with only a slight 2-month improvement in PFS for the combination arm, which was not statistically significant. Furthermore, the combination treatment was associated with increased toxicity, making it a less favourable option compared to olaparib monotherapy. Future trials, such as the NIRVANA trial, which is exploring niraparib with or without bevacizumab in the first-line setting, are being awaited to evaluate this strategy further.