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No Benefit From Second Surgery in Recurrent Ovarian Ca

— Neither PFS nor OS improved versus systemic therapy without surgery

MedpageToday

Secondary surgery for recurrent ovarian cancer failed to improve survival as compared with chemotherapy alone, final results of a large randomized trial showed.

In fact, surgery followed by chemotherapy was associated with an overall survival (OS) that was more than a year shorter versus the patients who received chemotherapy without surgery (50.6 vs 64.7 months). Adjustment for platinum-free interval (PFI) and choice of chemotherapy did not change the results. Surgery did lead to a small, nonsignificant improvement in progression-free survival (PFS).

Surgery was associated with a 30-day complication rate of 9%, including one fatal complication, reported Robert L. Coleman, MD, of the MD Anderson Cancer Center in Houston, and colleagues in the .

"Patients who benefit from surgery are those who have all of the tumor removed," Coleman told app. "When we looked only at those patients who got complete cytoreduction, we confirmed that. We confirmed that patients who had residual tumor did not get a benefit, and in fact, they were actually harmed. Then we took the best of the best, that is, we allowed the physicians to pick the patients who were the best fit for surgery, and we compared them to everyone who got chemo, [and] we still did not see a benefit."

"These findings would call into question whether our clinical judgment is specific enough to find that cohort of patients who will benefit from surgery," he added.

The findings confirmed an initial report from the trial presented at the 2018 American Society of Clinical Oncology (ASCO) meeting, showing no significant improvement in OS or PFS with surgery. The outcome had some similarities with the DESKTOP III trial from Germany, which showed no survival benefit with surgery and a PFS advantage only in the subgroup of patients whose surgery achieved at least minimal residual disease. Follow-up for OS is continuing in DESKTOP III.

Multiple meta-analyses have suggested a survival benefit with primary cytoreductive surgery for newly diagnosed ovarian cancer. However, no prior randomized trial had demonstrated significant improvement in survival with surgery, Coleman and colleagues noted.

More than 80% of women have disease recurrence, and 10-year disease-free survival for recurrent disease is <15%. Given the "abysmal" long-term outcomes associated with recurrent disease and the widespread adoption of primary surgical cytoreduction, support for second surgery at first recurrence should come as no surprise, the authors continued. Secondary surgery is particularly attractive for patients who have prolonged PFIs and isolated or limited-volume disease at recurrence. The National Comprehensive Cancer Network guidelines include secondary cytoreduction as an option for patients with a PFI ≥6 months.

"A clear limitation of this body of evidence is bias in patient selection, which is not easily controlled without a randomized clinical trial," the authors noted. "Furthermore, with the availability of bevacizumab (Avastin) and PARP inhibitors as maintenance medical treatments with proven progression-free survival benefit among patients with platinum-sensitive, recurrent ovarian cancer who have a response to salvage therapy, it is important to clarify the role of secondary cytoreductive surgery in this disease."

Investigators in GOG-0213 enrolled and randomized 485 patients with recurrent, platinum-sensitive ovarian cancer. Eligible patients had a PFI ≥6 months with first-line therapy and investigator-determined resectable disease (to no macroscopic residual disease). Patients randomized to the surgical arm received adjuvant platinum-based chemotherapy plus bevacizumab followed by bevacizumab maintenance. Those randomized to no surgery received the same systemic regimen. The trial had a primary endpoint of OS.

Complete resection occurred in 67% of patients assigned to secondary cytoreduction, and 84% of patients in both groups combined received the planned systemic therapy, with no difference between groups.

After a median follow-up of 48.1 months, surgery plus systemic therapy was associated with a hazard ratio (HR) for survival of 1.29 versus patients who received only systemic therapy (95% CI 0.97-1.72, P=0.08). Median OS was 50.6 months with surgery and 64.7 months without. The data yielded an HR for disease progression or death of 0.82 in favor of surgery, but the difference did not achieve statistical significance (95% CI 0.66-1.01). Median PFS was 18.9 months with surgery and 16.2 months without. Patient-reported quality of life decreased significantly after surgery but did not differ significantly between treatment groups after recovery.

Coleman noted that DESKTOP III showed a 5-month difference in median PFS in favor of the surgical arm (19 vs 14 months). On the basis of the GOG-0213 results, the chemotherapy arm of DESKTOP III might have underperformed. That might reflect a difference in treatment practices in the U.S. and Germany, he added. In GOG-0213, more than 80% of patients received bevacizumab, as compared with 20% of the DESKTOP III patient population.

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    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined app in 2007.

Disclosures

GOG-0213 was supported by the National Cancer Institute. Genentech provided bevacizumab for the trial.

Coleman disclosed relevant relationships with AstraZeneca, Merck, Tesaro, Medivation, Clovis Oncology, GamaMabs, Genmab, Roche/Genentech, Janssen, Agenus, Regeneron, OncoQuest, the V-Foundation, the Gateway Foundation, as well as support from the Ann Rife Cox Chair in Gynecology and the Judy Rees/Albert Pisani MD Ovarian Cancer Research Fund.

Primary Source

New England Journal of Medicine

Coleman RL, et al "Secondary surgical cytoreduction for recurrent ovarian cancer" N Engl J Med 2019;381:1929-1939.