DESKTOP III became the first phase III, prospective, randomized trial to show an association between improved overall survival (OS) and secondary cytoreductive surgery in women with platinum-sensitive recurrent ovarian cancer (PSROC), offering hope for people with a condition that results in nearly 14,000 deaths annually. Data were presented during the ASCO20 Virtual Scientific Program (Abstract 6000) by lead study author Andreas du Bois, MD, PhD, of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) and Evangelische Kliniken Essen-Mitte, Germany.
Secondary cytoreductive surgery is a widely used yet under-researched treatment approach in managing PSROC. Prospective, randomized trials have been lacking in this area but could help clarify the role and outcomes of debulking as well as identify appropriate patients for cytoreduction.
As such, the AGO DESKTOP I and II trials informed the development of selection criteria to predict optimal candidates for debulking in PSROC.1,2 The multicenter, international DESKTOP III trial (NCT01166737) then prospectively examined OS, progression-free survival (PFS), resection rate, and morality associated with the selection criteria developed in DESKTOP I and affirmed in DESKTOP II. Selection criteria included the AGO score based on an ECOG Performance Status score of 0, complete resection during first-line therapy, and ascites of < 500 mL.
In DESKTOP III, 407 patients with a platinum-free interval of more than 6 months and a positive AGO score were randomly assigned to either cytoreductive surgery with maximal effort toward complete resection (206 patients) or no surgery (201 patients).
“I am really happy to show a highly significant positive result of this trial,” Dr. du Bois said. “The median OS in the surgery arm was 53.7 months compared to 46 months in the no-surgery arm. This translates into a risk reduction of 25%, which was highly statistically significant. And the median OS gain between both arms was 8 months.”
“I am really happy to show a highly significant positive result of this trial,” Dr. du Bois said.
Dr. du Bois reported similar positive findings in PFS, which indicated a risk reduction of 34% and a median survival of 18.4 months in the surgery arm compared with 14.0 months in the no-surgery arm (HR 0.66, 95% CI [0.54, 0.82]; p < 0.001).
Positive outcomes in both endpoints appear largely due to the subgroup of surgical patients without residual disease.
“There was a huge impact of complete resection, which was achieved in [approximately] 75% of patients and ended up in a median OS exceeding 5 years after diagnosis of recurrent ovarian cancer, compared to only 28.8 months in those who ended surgery with residual disease,” Dr. du Bois said. “That translates into a risk reduction of 60%.”
Discussant Robert L. Coleman, MD, of US Oncology Research, noted that, compared with other similar secondary cytoreductive surgery trials such as SOC-1 (NCT01611766), debulking consistently appeared to have a favorable impact on mortality. Although only DESKTOP III met its primary endpoint of improving OS, both DESKTOP and SOC-1 demonstrated an added benefit of PFS.
“Both [trials] tout that the use of the triage algorithm to select patients for surgery can lead to complete gross resection in nearly three-quarters of patients; however, the price paid for being wrong is substantial, with no benefit seen in PFS and possibly a detriment in OS,” he added.
Interestingly, survival benefits of surgery were not observed in the GOG-213 trial, in which patients in both the treatment and control arms demonstrated remarkably similar median OS (Figure) and PFS results.3
“It is clear that the detrimental effects of the failed surgical attempt must be considered in patient selection. Better biological understanding of tumor microenvironment also will help to better position all modalities of therapy into the current setting,” Dr. Coleman said. “Formal analytics among these three trials is warranted and is planned to better elucidate potential subgroups of surgical merit.”
– Emily A. Kuhl, PhD
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου