Neoadjuvant Chemotherapy Could Improve Outcomes in Ovarian Cancer

R. Wendel Naumann, MD

Although survival data have not yet indicated superiority for neoadjuvant chemotherapy in patients with ovarian cancer, R. Wendel Naumann, MD, said it remains a reasonable approach as it decreases the morbidity of surgery.

Despite the lack of a survival benefit, recent data have demonstrated the noninferiority of the approach. For example, the SCORPION trial evaluated upfront surgery versus neoadjuvant chemotherapy followed with surgery for patients with advanced epithelial ovarian cancer with a high tumor load. Data showed no significant difference in progression-free survival between the 2 treatment strategies.

Naumann explained that part of the difficulty in producing better survival data in these neoadjuvant studies is that patients enrolled on the trials are usually those with a poor prognostic outlook, overall.

OncLive: What is the current role of surgery in the ovarian cancer space?

In an interview with OncLive^® at the 2018 State of the Science Summit^TM on Ovarian Cancer, Naumann, director of Minimally Invasive Surgery in Gynecologic Oncology at Carolinas Medical Center, Atrium Health, discussed the use of neoadjuvant chemotherapy and surgery for patients with ovarian cancer.Naumann: Surgery is obviously an important part of ovarian cancer treatment. The traditional paradigm has been doing surgery first followed by chemotherapy. We have emerging evidence that giving chemotherapy before surgery is a very reasonable option. It has been shown to decrease the morbidity of surgery. We can also improve the optimal and complete resection rate at the time of surgery. The criticism of some of these trials has been that the survival data is a little less than what we expect, but this is because the patients we choose to give neoadjuvant chemotherapy to are patients who do poorly in general.

Is there an optimal neoadjuvant chemotherapy regimen you give your patients?

Could PARP inhibitors find a place in the neoadjuvant setting?

We have now had 4 randomized trials showing this is a reasonable approach, with at least an equivalent outcome to primary debulking. It’s becoming more of a personal choice. In our institution, we're using minimally invasive surgery to accomplish this, so we can actually reduce the morbidity and mortality from primary surgery.In the last few years, we have come full circle. Paclitaxel and carboplatin [became available] in 1996, and we have had several trials with other chemotherapy regimens. We found that all of the other ones don't improve outcomes. The new approval of bevacizumab (Avastin) in the upfront setting, particularly for poor-prognosis patients, is probably a good thing in terms of improving their outcomes. That is the patient population we would all agree needs neoadjuvant chemotherapy. We have never been able to show that adding something upfront, whether it's an additional chemotherapy agent or an anti-VEGF agent, has improved survival. However, we can at least improve response rates and increase the amount of time these patients have before the cancer comes back.I don't know about the neoadjuvant setting, but this will at least be true in the upfront setting. The SOLO-1 trial is supposed to be read out shortly; we will see data from it at the 2018 ESMO Congress. The press release has already stated that it's a positive trial. There are other trials ongoing that are testing these drugs in the frontline setting.

Has there been an evolution of surgical techniques in ovarian cancer?

What exciting data in ovarian cancer were presented at the 2018 ASCO Annual Meeting?

As far as the neoadjuvant setting goes, it will likely be induction chemotherapy followed by whatever additional agent you have to treat your patients.The biggest aspect of that has been minimally invasive surgery. This has been driven by the push to do better and less morbid surgery. The problem is that we don't really appreciate what the mortality of upfront surgery could be—it's about 5% to 8%. That is a big deal for patients who may not be the best surgical candidates. We push ourselves to do optimal resection, but we have to keep in mind that there's a tradeoff in terms of morbidity and even mortality.Two trials were the Japanese JCOG-0602 trial and the SCORPION trial, which were fully reported in terms of surgery. The JCOG-0602 trial was a study of upfront surgery versus interval surgical debulking with neoadjuvant chemotherapy. It was an equivalence trial. It did not show any difference in outcome.

Are there any ongoing trials in this space?

What do you envision the role of surgery being in ovarian cancer 5 to 10 years down the line?

The SCORPION trial was a superiority study. A laparoscopy was conducted and patients got a score. Therefore, the patients who knew they could not be completely resected would then be randomized to primary surgery or neoadjuvant chemotherapy. When they did neoadjuvant chemotherapy, they found there was a higher resection rate, between 93% and 100%. The idea was if you couldn't completely resect a patient, perhaps you could improve their outcome. The data did not show superiority; it was a negative trial. We're now at 4 randomized trials, and none of them has shown that neoadjuvant chemotherapy is superior to upfront surgery.Most of the trials are attempting to optimize the chemotherapy for patients, mostly after surgery. Carboplatin and paclitaxel work so well that it's going to be difficult to improve upon that in the short term. However, long term, we certainly have options with bevacizumab being approved and with the PARP inhibitors probably being approved soon. We're also moving toward immuno-oncology to see if this can improve progression-free survival and overall survival.Surgery probably won't change because we know it's a very important part of ovarian cancer treatment. People will probably move more in the direction of neoadjuvant chemotherapy followed by surgery; this is not because the outcomes are different, but the morbidity is less. It also probably costs less to do it that way because there is less intensive care.

Fagotti A, Vizzielli G, Ferrandina G, et al. Survival analyses from a randomized trial of primary debulking surgery versus neoadjuvant chemotherapy for advanced epithelial ovarian cancer with high tumor load (SCORPION trial). J Clin Oncol. 2018;36(suppl 15; abstr 5516). meetinglibrary.asco.org/record/160515/abstract.