Neoadjuvant Chemo Favored in Advanced Ovarian Cancer

Pam Harrison

September 09, 2016

The use of neoadjuvant chemotherapy (NACT) for the treatment of ovarian cancer is increasing in academic centers across the United States, but it is increasing to a greater extent in women with stage IV disease, who are less likely to achieve optimal cytoreduction with up-front surgery than those with earlier-stage disease, an observational study indicates.

The study was published online September 6 in the Journal of Clinical Oncology.

"We found no survival difference in patients with stage IV disease, whether they were treated with surgery or NACT first," lead author Larissa Meyer, MD, the University of Texas MD Anderson Cancer Center, Houston, told Medscape Medical News.

"Additionally, women who received NACT in our study population were less likely to require ICU [intensive care unit] care or rehospitalization after surgery," she added.

"So I think our findings are really quite concordant with the recent position paper, which essentially states the same thing," Dr Meyer commented.

The American Society of Clinical Oncology and the Society of Gynecologic Oncology (ASCO/SGO) recently released a position paper on the use of NACT in advanced ovarian cancer, which was published online August 8 in the Journal of Clinical Oncology and Gynecologic Oncology.

According to the position paper, NACT is the preferred treatment option for women with advanced ovarian cancer if it is unlikely that primary cytoreductive surgery (PCS) can reduce disease to <1 cm.

Conversely, for women for whom there is a high likelihood of achieving cytoreduction to <1 cm and, ideally, to no visible disease and for whom morbidity is acceptable, PCS is recommended over NACT.

The joint position paper also indicates that NACT is a viable alternative to up-front surgery for women with potentially resectable disease who prefer the neoadjuvant approach, as chemotherapy is not inferior to surgery in terms of progression-free or overall survival (OS) in this patient group.

The position paper did not differentiate between stage IIIC and stage IV disease but simply categorized patients as having "advanced" ovarian cancer or not.

"The position paper had very strict criteria and used randomized control trial data, so we didn't use any of the data from our observational study to color the position paper, because the methodology was very different," Dr Meyer explained. Dr Meyer was a coauthor of the ASCO/SGO position paper; several other authors on the position paper were also involved in the current observational study.

A one-size-fits-all strategy doesn't work for ovarian cancer. Dr Larissa Meyer

"The bottom line is that a one-size-fits-all strategy doesn't work for ovarian cancer," Dr Meyer added.

"What we are saying is that each person needs to be individually evaluated by someone who can best estimate the risks and benefits of up-front surgery. You can't categorize people strictly by stage," she said.

Observational Study

For the observational study, Dr Meyer and colleagues identified patients who had been diagnosed with either stage IIIC or stage IV ovarian cancer and who underwent NACT or PCS at one of six National Cancer Institute–designated cancer centers in the United States between 2003 and 2012.

Outcomes following NACT were analyzed in 1538 patients who received treatment within 12 weeks of being diagnosed with ovarian cancer.

The researchers also compared outcomes associated with NACT with those following PCS in 1158 patients from the same cohort. They excluded patients who were treated with either intraperitoneal and intravenous (IP/IV) chemotherapy, as IP/IV chemotherapy is associated with an independent survival benefit, the authors point out.

"In women with stage IIIC disease, NACT use increased from 16% during 2003 to 2010 to 34% during 2011 to 2012 (Ptrend<.001)," they report.

Use of NACT increased to a significantly greater extent for women with stage IV disease. For those patients, the use of NACT increased from 41% during the period 2003 to 2010 and to 62% between 2011 and 2012 (Ptrend<.001).

However, among the six academic cancer centers analyzed, there was considerable variability in the use of NACT overall. Use ranged from 8% to 30% for women with stage IIIC disease (P < .001) and from 27% to 61% for women with stage IV disease (P = .007).

NACT and Survival Data

Importantly, OS was significantly compromised in women with stage IIIC disease who received NACT. For those patients, the use of NACT was associated with a 40% decrease in OS at a median of 33 months compared with a median of 43 months for women treated with PCS, the authors point out.

In contrast, median OS in women with stage IV disease who received NACT was not significantly better at a median of 31 months than it was for PCS-treated patients at a median of 36 months.

Results were unchanged when investigators analyzed women who had a high disease burden, for whom the association between PCS and increased OS among stage IIIC patients prevailed.

On the other hand, stage IIIC patients who received NACT were significantly less likely to require admission to an ICU, at 1.1% in comparison with 8% for their PCS counterparts, or to be rehospitalized, at 4.6% in comparison with 12.1% (P = . 01 for both endpoints).

Results were similar among patients with stage IV disease, the authors note.

"In the position paper, the authors point out that NACT is associated with less peri- and postoperative morbidity and mortality and shorter hospitalization than PCS, and findings from our study support this statement," Dr Meyer told Medscape Medical News.

"So I think what we're trying to get at is very similar to what the guidelines state, in that each individual needs to be looked at by people with the appropriate expertise so that the right patient can be offered up-front surgery to benefit from its survival advantage, even though there is more risk, and you want to minimize that risk in patients you don't think will benefit from it," she concluded.

Less Serious Adverse Events

Asked by Medscape Medical News to comment on the study, Maurie Markman, MD, president, Cancer Treatment Centers of America Medicine and Science, Philadelphia, Pennsylvania, noted that, to date, NACT has been shown to result in equivalent survival and less serious adverse events compared with PCS in several well-conducted phase 3 randomized trials.

"The [current] observational study revealing superior survival in stage III disease with primary surgery is unfortunately one more example of the inappropriateness of such efforts in directly comparing outcomes," Dr Markman commented in an email.

"Patient selection bias ― better known as 'good clinical care' ― will heavily impact outcomes, and it is simply invalid to attempt to compare survival in such a retrospective analysis," he added.

The study was supported by grants from the National Cancer Institute and the Cancer Prevention and Research Institute of Texas. Dr Meyer has received honoraria from TRM Oncology and research funding from AstraZeneca. Other authors' relevant financial relationships are listed in the original article. Dr Markman has served as a director, officer, partner, employee, advisor, consultant, or trustee for Celgene Corporation; Amgen Inc; Crititech; and Millennium Pharmaceuticals, Inc. He has also served as a speaker or a member of a speakers' bureau for Genentech, Inc.

J Clin Oncol. Published online September 6, 2016. Abstract


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