Researchers from The University of Texas MD Anderson Cancer Center reported the findings on the survival outcomes using two different medical regimens for patients with platinum-sensitive recurrent ovarian cancer: 1) performing a second surgery in addition to chemotherapy, and 2) prescribing chemotherapy without a second surgery. The study concluded that secondary tumor reduction, or cytoreduction, surgery followed by chemotherapy did not result in a longer survival outcome than a singular regimen of chemotherapy in patients with platinum-sensitive recurrent ovarian cancer, said lead investigator Robert L. Coleman, MD, Professor of Gynecologic Oncology and Reproductive Medicine.
“Surgical cytoreduction is recognized as a key component of frontline treatment for primary ovarian cancer, but its role in recurrent disease, while it has been touted as beneficial, had not been formally tested,” explained Coleman. “This research is the first randomized clinical trial to report in this setting and shows that secondary cytoreduction does not benefit these patients.”
According to the National Cancer Comprehensive Network 2019 Guidelines for Patients, Ovarian Cancer, surgery may remove all or part of organs or tissues to which the cancer has spread.
“This is called debulking surgery or cytoreductive surgery,” said Coleman. “In women who are willing and have disease distribution amenable to removal, surgery is the recommended initial treatment for stage II, III, or IV ovarian cancer. This is then followed by a regimen of platinum-based combination therapy with consideration for maintenance therapy.
There were two primary objectives for the current trial. The first, reported in 2017, was to determine if bevacizumab added to platinum-based alone. This was confirmed. The second and the focus of this current publication was determine if secondary cytoreduction before platinum-based chemotherapy extended overall survival, said Coleman.
The principle eligibility were 1) platinum-sensitive, recurrent ovarian, fallopian tube and primary peritoneal cancer; 2) had a complete response to at least 3 cycles of primary platinum-based chemotherapy with a normal CA125 (J Clin Oncol 2018;36, no. 15_suppl:5501-5501); and 3) had disease distribution, which in the opinion of the investigator was amenable to surgical cytoreduction to no gross residual disease.
“About half of the approximate 50,000 prevalent (platinum-sensitive recurrent patients) in 2018 could have data met the criteria for the randomized trial,” said Coleman. “The discount represents surgically amenable patients based on our criteria.”
According to Coleman, the overall survival (OS) was 50.6 months in the surgery group and 64.7 months in the non-surgery group. The median progression-free survival (PFS) was 18.9 months with surgery versus 16.2 months without it. The percentage of patients surviving at 3 years was 67 percent in the surgery group and 74 percent in the non-surgery group.
Multiple Adjuvant Treatment Regimens
According to Coleman, the early results of the study were first presented at the 2018 ASCO Annual Meeting. When asked about responses about his presentation, Coleman noted, “It was what you might expect in a situation where the prevailing opinion and practice is to offer secondary cytoreduction as an option. Throughout the meeting, there were specific questions raised in rebuttal, such as the targeted patient population, criteria for patient selection, post-operative therapy, and comparisons to DESKTOP3, which was presented (secondary endpoint of PFS) 1 year earlier,” he said.
He also said it was expected that DESKTOP3 should mature soon with results anticipated in the next 6 months. While the two trials share many similarities, evaluation of results across the two trials will be important to better understand the value of surgery in this setting.
“It is very important to emphasize that both GOG-213 (Gynecol Oncol 2016;142(3):471-476) and DESKTOP3 have as their primary out measure overall survival, said Coleman. “With the ever-increasing availability of multiple effective adjuvant treatment regimens, this endpoint is being affected by several other factors than surgery.”
During the research study, Coleman shared two major events which may have impacted the results: 1) the documentation of the benefit of bevacizumab added to chemotherapy, and 2) the availability of poly ADP-ribose polymerase [PARP] inhibitors.
“Both have had a substantial impact on post-progression survival which is critical in evaluating OS when differences are seen in PFS,” he added.
The international randomized trial included women with platinum-sensitive, epithelial recurrent ovarian, primary peritoneal, or fallopian tube cancer who had a complete clinical response to at least 3 cycles of primary platinum-based chemotherapy and a normal serum CA-125 value, according to the research.
The Globacon 2018 online database reported a 2012 global 5-year prevalence at 586,000, said Coleman.
“But the U.S. estimates were very low compared to Surveillance, Epidemiology, and End Results (SEER) Program results; in 2012, SEER estimates of prevalence was about 3 times higher (~191,000 women vs. ~60,000 women) and may represent contribution of patients surviving past 5 years,” he explained. “So their 5-year prevalence number is likely very conservative. It is also influenced dramatically by availability and the use of new agents which are not equally available around the world.”
Amy Gallagher is a contributing writer.
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