Phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer
Dr Helen Mackay - Sunnybrook Research Institute, Toronto, Canada
Thank you. And I would just like to thank the organisers for giving us this opportunity to discuss the OV21/PETROC data and I present this on behalf of my co-authors and investigators.
Epithelial ovarian cancer is the fifth most common cancer affecting women. Unfortunately we lack a population based screening tool and the early stages of this disease are often asymptomatic. As a result, approximately two-thirds of women will present with stage 3 or 4 cancer, mortality rates are high. Previous published randomised trials of intraperitoneal delivery of chemotherapy have demonstrated a reduction in the risk of death for select patients undergoing up-front optimal cytoreductive surgery. Recently we have seen an increase in the delivery of chemotherapy prior to a definitive surgical attempt, so-called neoadjuvant chemotherapy, and this is often occurring in our most advanced case patients.
OV21/PETROC was a pragmatic study designed to answer the question do these patients benefit from the delivery of intraperitoneal chemotherapy. OV21/PETROC was a two stage study with patients randomised at the time of surgery either to receive an intravenous arm containing standard of care drugs carboplatin, paclitaxel with IV paclitaxel delivered on day 8, or one of two experimental arms containing intraperitoneal delivery of, in the case of arm 2, cisplatin and, in the case of arm three, carboplatin. Both paclitaxel was given intravenously and by the intraperitoneal route on day 8. The reason for these two experimental arms is that in the randomised trial data to date intraperitoneal cisplatin had been used and one of the contributing causes to the limited uptake of IP therapy is the tolerability of intraperitoneal cisplatin. At the end of the first stage of this trial the Independent Data Safety and Monitoring Committee advised us to continue into the second phase of the study with the intraperitoneal carboplatin arm. This was based on both toxicity data, better tolerability and also on efficacy. A hundred patients were randomised to each of the intravenous arm and the intraperitoneal carboplatin arm. The primary endpoint was the progressive disease rate at nine months. In the intravenous arm this was 42.2% and in the intraperitoneal carboplatin arm this was 23.3%. This is an 18.9% reduction in progressive disease rate at nine months.
This trial was not powered to detect a difference in overall survival, that being said, the hazard ratio is similar to that that we’ve seen in other intraperitoneal trials. Also, the median overall survival in terms of the IV therapy is similar to that seen in similar populations in neoadjuvant studies. I would remind you that this randomisation takes place at the time of surgery so those patients have had neoadjuvant chemotherapy before receiving their surgery. The median overall survival was 59.3 months in the IP arm. Of course, tolerability and quality of life is important and the IP carboplatin arm was well tolerated. Quality of life data did not differ between the IV and IP arms and improved with time.
So, in conclusion, what we have demonstrated is the tolerability and efficacy of the intraperitoneal carboplatin containing regimen compared to intraperitoneal cisplatin. Our primary endpoint was met and although we were not powered for overall survival I think these data, taken in the context of other intraperitoneal studies, give information to both patients and clinicians on how to incorporate this treatment in women undergoing neoadjuvant treatment. Moving forward, we hope to better define an identifier predictive signature by looking at correlative studies associated with tissue samples collected during the study. Thank you.