Neoadjuvant Chemo Shows Comparable Data to Upfront Surgery in Ovarian Cancer

Michelle M. Boisen, MD

Recent trials, such as the SCORPION study, continue to compare the outcomes of patients who undergo upfront surgery versus neoadjuvant chemotherapy in ovarian cancer, and could address unanswered questions in the community, explained Michelle M. Boisen, MD.

The phase III SCORPION trial compared neoadjuvant chemotherapy followed by surgery and adjuvant therapy versus upfront surgery and adjuvant surgery in patients with advanced ovarian cancer. The study addressed controversy found in similar trials, in which some believed there were suboptimal surgeries and compromised overall outcomes, Boisen said.

“It seems that the surgical effort was more robust and the outcomes were comparatively better,” said Boisen, an assistant professor in the Department of Obstetrics, Gynecology and Reproductive Sciences at University of Pittsburgh Medical Center. “However, between the two patient groups overall, there doesn't seem to be much of a difference.”

Results of a survival analysis from the trial showed that the progression-free survival in patients who underwent primary debulking therapy versus neoadjuvant chemotherapy was 15 months versus 14 months (HR, 1.06; 95% CI, 0.77-1.46; P = 0.72). The median overall survival was 41 months in the primary debulking arm and not reached in the neoadjuvant therapy arm. Additionally, optimal residual tumor (≤1 cm) was obtained in 92.8% for primary debulking patients versus 100% for neoadjuvant therapy patients (P = .02) , and primary debulking had 7 registered deaths for postoperative complications compared with 0 in the neoadjuvant therapy arm.

In an interview during the 2019 OncLive^® State of the Science Summit™ on Ovarian Cancer and Soft Tissue Sarcoma, Boisen discussed the role of neoadjuvant chemotherapy in advanced ovarian cancer and data comparing outcomes with this modality versus upfront surgery.

OncLive: How could the role of neoadjuvant chemotherapy affect surgery’s role in ovarian cancer?

Boisen: There are a couple of randomized trials that were published 5 to 10 years ago that attempted to compare upfront surgery with neoadjuvant chemotherapy. As a result of these studies, we know people who had neoadjuvant chemotherapy have less surgical morbidity than [patients who] undergo surgery. The question is how receiving neoadjuvant therapy as opposed to upfront surgery impacts their long-term prognosis. The prospective studies that we have definitive data on suggest that the outcomes are similar; however, there are some issues with the extent of surgery performed in each of the trials. Therefore, many [physicians] still believe that if a patient has upfront surgical debulking, [surgery] is the appropriate way to proceed.

What types of neoadjuvant regimens are researchers exploring?

Prospectively, the only chemotherapy regimens that have been studied are carboplatin with paclitaxel given in 21-day cycles. Nobody has prospectively looked at giving dose-dense or intraperitoneal regimens upfront. Now, researchers are looking to give neoadjuvant chemotherapy giving carboplatin/paclitaxel for 3 to 4 cycles followed by surgical debulking.

Could you highlight some key studies evaluating neoadjuvant chemotherapy?

The 2 prospective studies that have been published are the EORTC trial 55971, published in 2010, and the CHORUS trial. Both of those trials were published out of Europe in the last decade. They compared a very nice regimen of neoadjuvant chemotherapy followed by surgery followed by adjuvant therapy with upfront debulking followed by adjuvant therapy.

Additionally, there are 2 trials that have only been published in abstract form: SCORPION and GOG-0213. They look at similar populations of patients with a more aggressive surgical effort to attempt to eliminate the criticism of the EORTC 55971 and CHORUS trials.

What are some of the criticisms regarding these trials and how are they being addressed?

EORTC 55971 and CHORUS looked at a very similar population of patients with advanced ovarian cancers and randomized them to neoadjuvant chemotherapy followed by surgery followed by adjuvant chemotherapy versus upfront debulking followed by adjuvant chemotherapy. These trials found there is not a difference in overall survival between the groups that receive neoadjuvant therapy versus those that undergo upfront surgery.

However, the criticisms of those 2 trials are the operating time and that the surgical effort that went into debulking these patients were potentially suboptimal, compromising outcomes overall. [Some physicians believe the surgical effort in the studies] was not equivalent to the surgical effort that would go into surgery at other institutions in the United States. The SCORPION trial and the GOG-0213 trial attempted to correct for that.

In your own practice, how are you selecting patients for each of the approaches?

Surgical candidacy, from a health standpoint, of the patient is really important. The first thing I triage is whether this patient is likely to come through a big surgery with minimal morbidity. Am I going to be able to get this patient to chemotherapy after surgery and not have them end up in a nursing home for a long period of time, or run the risk that they're never going to be able to receive chemotherapy? If a patient is a poor surgical candidate from that standpoint, we are typically triaging to neoadjuvant therapy.

Other patients who would go immediately to neoadjuvant therapy are patients who have stage IVb disease where their disease is not going to be clinically resectable at the time of surgery. However, with some patients who have advanced disease, it is a little bit unclear whether they are surgically resectable. In those cases, I offer a diagnostic laparoscopy as a triage to neoadjuvant chemotherapy versus upfront surgery.

Could you expand on how you are using the laparoscopy as a diagnostic tactic?

There were trials that were published a couple of years ago that looked at trying to develop a scoring system, in an effort to predict how likely a patient would be optimally debulked. The goal of all of these surgeries should be to get patients to at least less than 1 cm of residual disease with, ideally, no visual residual disease.

A scoring system was developed based on the location of patient's disease and [determined that] if a patient scores <8 versus >8, their chance of being optimally debulked is “X”. We do something similar. We put the scope in, take a look around, and assess the disease on the diaphragm, the liver surface, and the stomach. We score patients based on that and triage patients accordingly.

What is your takeaway message for your colleagues in this field?

The take-home message in this setting of considering neoadjuvant chemotherapy is the shared decision making between the medical oncologist and the patient is key. The best we can say [about the findings] from these prospective trials is that the outcomes are relatively similar, regardless of the approach that you take.

The surgical candidacy of the patient and the bulk of disease should come into play [when making a treatment decision]. Ultimately, what we want to avoid is all patients with advanced disease getting automatically dispositioned to neoadjuvant chemotherapy, because there is probably a subset of patients who benefit from upfront surgery. Having the input of the gynecologic oncologist in that decision is key.

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; abstr 5516). doi: 10.1200/JCO.2018.36.15_suppl.5516.