What is the role of neoadjuvant chemotherapy in advanced epithelial ovarian cancer (EOC) ?

There are 2 phase III trials on neoadjuvant chemotherapy in advanced EOC. The EORTC 5597136randomised 718 women with stage III or IV ovarian cancer to neoadjuvant chemotherapy followed by interval debulking surgery or primary debulking surgery. There were no significant differences between the study groups with regards to OS (HR 0.98, 95% CI 0.82-1.18) or PFS (HR 1.01, 95% CI 0.86-1.17). In the EORTC 55971 study, there was increased debulking rate and reduced surgical complications in the neoadjuvant chemotherapy group. In the CHORUS study, a phase III randomized trial to investigate the timing of initial surgery in ovarian cancer37, patients with clinical stage III or IV ovarian cancer were randomized to primary surgery followed by 6 cycles of platinum-based chemotherapy or 3 cycles of neoadjuvant chemotherapy followed by surgery before another 3 cycles of platinum-based chemotherapy. CHORUSwas designed to demonstrate non-inferiority of neoadjuvant chemotherapy based on a 3 year survival of 50% with primary debulking surgery. 550 women were randomized. Median tumour size was 8 cm, 25% FIGO IV and 19% WHO performance status 2. At a median follow-up of 3 years, the OS is superior for the neoadjuvant chemotherapy group (24.5 months versus 22.8 months, HR of 0.87, 80% CI 0.76-0.98).

No cost-effectiveness analysis was done.

With regard to the EORTC trial, we are mindful of the fact that the accrued patients have very extensive and bulky disease as 73% had tumours of >5cm and 47% had tumours of >10 cm at randomisation. Similarly, the median size of tumour in the CHORUS trial was 8 cm. Hence, the results of the trials on the role of neoadjuvant chemotherapy cannot be extrapolated to patients with less bulky disease. Furthermore, in a post hoc analysis in the EORTC trial, amongst patients with metastatic disease <5 cm in diameter at randomization, the OS was slightly longer in the primary surgery group than in the neoadjuvant chemotherapy group (HR=0.64, 95% CI 0.45-0.93). Hence, rather than recommending neoadjuvant chemotherapy as an alternative for ovarian cancer patients with any stage or disease bulk, it is preferable to reserve neoadjuvant chemotherapy for selected patients with bulky stage III or IV disease, at the same time taking into account the resectability, age, stage, histology and performance status.38

SCAN Workgroup Recommendations for Neoadjuvant Chemotherapy in Advanced EOC

All members of the workgroup unanimously voted for the NCCN guidelines as it endorses the use of neoadjuvant chemotherapy in patients who are poor surgical candidates due to co-morbidities and disease factors. The NCCN recommends the involvement of gynaecologic oncologists in deciding if neoadjuvant chemotherapy should be given. As it does not specify the neoadjuvant chemotherapy regimen, it accommodates for the treating oncologist to make the judgement that best suits the patients interests as some patients may not be able to tolerate standard combination chemotherapy.