Alexandra Leary, MD, PhD

Alexandra Leary, MD, PhD, of the Gustave Roussy Institute of Oncology, Paris, underscored the controversy surrounding the use of neoadjuvant chemotherapy in advanced ovarian cancer, suggesting the discord may be “more cultural and emotional than scientific” to some degree. “Some countries, such as Germany, won’t use any neoadjuvant chemotherapy, whereas others, like France, use it frequently,” said Dr. Leary. “The United States avoided this approach for a long time, but clearly, it has shifted its practices.”

According to Dr. Leary, the main concern regarding neoadjuvant chemotherapy has been the development of resistant subclones in bulky tumors, which are known to be heterogeneous. However, the evidence supporting this hypothesis and the potentially negative impact on prognosis has been limited.

Early vs Advanced Disease

“The authors of this cross-sectional analysis limited themselves to the right cohort of patients, which is those with stage III and IV disease,” said Dr. Leary, who added there is no debate about the use of neoadjuvant chemotherapy in early-stage ovarian cancer. “You should always operate upfront in early-stage disease unless you can’t debulk completely or the patient is too fragile.”

With respect to advanced disease, Dr. Leary noted the steady improvement in overall survival over the past decade could be due to a number of reasons, but there is no evidence the increased uptake of neoadjuvant chemotherapy has had a negative impact on survival.

“The angle of improvement in overall survival is completely stable, which shows there is no deleterious impact to using neoadjuvant chemotherapy, but there is also no evidence it has a positive impact on overall survival,” she observed. “Interestingly, however, a recent publication looking at pooled results from two large randomized clinical trials comparing primary debulking to neoadjuvant chemotherapy showed an improvement in patients with stage IV disease who received neoadjuvant chemotherapy.”

Although these data may not settle the debate once and for all, Dr. Leary said she found it reassuring that both strategies are acceptable. She added, “ASCO published updated guidelines a few years ago to say that neoadjuvant chemotherapy is a perfectly reasonable approach and is actually a preferred approach in patients who are not completely operable upfront.” 

DISCLOSURE: Dr. Leary has received honoraria from AstraZeneca, Clovis Oncology, Tesaro, and PharmaMar; has served in a consulting or advisory role for AstraZeneca, Biocad, Clovis Oncology, GamaMabs Pharma, Gritstone, Pfizer, Seattle Genetics, and Tesaro; has received institutional research funding from AstraZeneca, Clovis Oncology, Genentech, Inivata, Merus, and MSD Oncology; and has been reimbursed for travel, accommodations, or other expenses by AstraZeneca.