Conference Coverage

DESKTOP III: Secondary surgery for recurrent OC improves PFS, TFST

 

Key clinical point: Secondary surgery improved PFS and time to first subsequent therapy in certain women with OC recurrence after a 6 month platin-free interval.

Major finding: Median progression-free survival was 19.6 vs. 14 months in the surgery vs. second-line chemotherapy-only arm.

Data source: The randomized phase III DESKTOP III study of 407 patients.

Disclosures: Dr. du Bois reported serving as a consultant or adviser for AstraZeneca, Mundipharma, Pfizer, Pharmamar, and Roche/Genentech.

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Complete resection is key

The findings from DESKTOP III complement those from prior retrospective studies, but one key difference is the emphasis on the importance of complete resection, abstract discussant Ritu Salani, MD, said at the meeting.

“I no longer believe that optimal resection is good enough in this patient population,” she said.

In fact, given that 67 patients in the study were not completely resected, it is important to look at whether there are any identifying factors that could help prevent surgery in these patients, and whether there are any minimally invasive or less invasive approaches, such as scoping and scoring these patients, to determine who really is completely resectable, she said.

Dr. Ritu Salani of Ohio State University, Columbus

Dr. Ritu Salani

“I think these results are really exciting, but we’ve been here before with platinum-sensitive disease, where progression-free survival has been favorable but doesn’t translate to overall survival ... so I just remind us that we have not passed the test yet,” she said.

Other studies of cytoreductive surgery, including GOG 213 and the Dutch SOCceR trial, are ongoing, and the primary endpoint of DESKTOP III is overall survival, she noted.

“We look forward to these data maturing.”

Dr. Salani is with the Ohio State University, Columbus. She has received honoraria from Clovis Oncology and Lynparza, and has served in a consulting or advisory role for Genentech/Roche.


 

At THE 2017 ASCO ANNUAL MEETING

– Secondary cytoreductive surgery resulted in a clinically meaningful increase in progression-free survival and time to first subsequent therapy in a phase III study of carefully selected women with ovarian cancer who experienced their first relapse after a platin-free interval of 6 months.

These interim findings from the randomized international DESKTOP III trial suggest that until final overall survival data are available to more definitively define the role of secondary cytoreductive surgery in this setting, it should at least be considered as an option in patients who are good candidates based on a positive AGO Study Group score, defined as an ECOG performance status score of 0, ascites of 500 mL or less, and complete resection at initial surgery, Andreas du Bois, MD, reported at the annual meeting of the American Society of Clinical Oncology.

The median progression-free survival (PFS) in 204 women who met this criteria and who were randomized to undergo surgery followed by chemotherapy was 19.6 months, compared with 14 months in 203 women who were randomized to receive only second-line chemotherapy (hazard ratio, 0.66), said Dr. du Bois of AGO and Kliniken Essen-Mitte, Essen, Germany.

“Even more important ... only complete resection makes a difference ... and that adds a median 7.2 months PFS with a hazard ratio of 0.56, which is highly significant. Fortunately that translates into time to first subsequent treatment, which is a more patient-oriented outcome,” he said.

The time to third-line therapy was prolonged by a highly statistically significant median of 7.1 month (hazard ratio, 0.6).

“What was the trade-off for these benefits? The patients did not pay for it with excessive mortality,” he said, explaining that no significant differences were seen between the groups in terms of mortality at 30, 60, 90, or 180 days, and that no excessive toxicity or treatment burden was seen in either group.

Dr. Ritu Salani

Median age of the patients was 60 years; they were enrolled at 80 centers in 12 countries between 2010 and 2015. The platin-free interval exceeded 12 months in 75% and 76% of patient in the surgery and control arms, respectively.

Chemotherapy regimens in both the treatment and control arms were selected according to institutional standards, although platinum-based combination therapy was strongly recommended; 87% and 88% in the groups, respectively, received a platinum-containing second-line therapy.

Macroscopic complete resection was achieved in 72.5% of patients in the surgery arm, which was the rate predicted by the AGO scores.

“We know that the surgery and chemotherapy are the cornerstones of ovarian cancer therapy ... however, surgery in recurrent ovarian cancer has not been based on high-level evidence,” Dr. du Bois said. “So far there are only retrospective series suggesting that there might be a benefit or not.”

The German AGO group and the Gynecologic Oncology Group (GOG) in the United States thus initiated clinical trials to evaluate its role in recurrent ovarian cancer, including the DESKTOP series, he explained, noting that the AGO score was developed through these trials as a way to identify good surgical candidates based on preoperative factors.

It was confirmed in a prospective study that the score, which selects about 50% of all patients with platinum-sensitive recurrent ovarian cancer, could predict successful surgery, he added.

In the current study, the data with respect to overall survival – the primary study endpoint – have not reached maturity, but at 2 years it was 83%.

However, the findings of a meaningful benefit in progression-free survival and time to first subsequent treatment (advantages of 5.6 and 7.1 months, respectively) in secondary cytoreductive surgery patients is at least comparable with all phase III trials in second-line therapy for platinum-sensitive recurrent ovarian cancer so far, he said.

“In fact, it’s the most positive trial ever reported in this population,” he added, noted that he was referring to therapy trials, not maintenance trials.

Further, the fact that the surgery benefit was exclusive to patients with complete resection indicates the importance of selecting both the right center with capability of achieving complete resection in most patients, and the right patients, as identified by the AGO score.

“Hopefully, further follow-up will show that this benefit translates into overall survival,” he concluded, noting that overall survival will be evaluated after extended follow-up when 244 overall survival events are observed.

Dr. Du Bois reported serving as a consultant or adviser for AstraZeneca, Mundipharma, Pfizer, Pharmamar, and Roche/Genentech.

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