Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: The DESKTOP III investigators report a significant overall survival (OS) benefit among relapsed ovarian cancer patients who underwent cytoreductive surgery before receipt of platinum-based chemotherapy compared with those given only the chemotherapy.
The trial recruited 407 patients who had experienced recurrence at least 6 months after their initial complete resection and platinum-based chemotherapy, and had a ECOG performance score of 0 and no more than 500 mL of ascites.
Thus, the participants met the AGO criteria “used to identify patients in whom a complete resection might be achieved”, explain Philipp Harter, from Kliniken Essen-Mitte in Germany, and co-authors in The New England Journal of Medicine.
They emphasize: “Appropriate selection of patients and trial centers was crucial for the success of this trial, and the importance of these selections is reflected in both the high efficacy and low morbidity in the trial.”
Overall, 76.7% of patients receiving cytoreductive surgery plus chemotherapy and 79.6% of patients given chemotherapy only received at least five cycles of second-line platinum-based chemotherapy. Bevacizumab was given to 47 patients in each arm but just eight and 12 of the surgery and chemotherapy-only groups, respectively, received a PARP inhibitor.
Of the 206 patients randomly assigned to undergo surgery, 192 underwent the procedure, with macroscopic complete resection achieved in 75.5% of these cases. Reoperation was required in 3.7% of patients and there were no deaths within 30 days of resection.
After a median 69.8 months of follow-up, the median OS was 53.7 months for the patients assigned to receive cytoreductive surgery plus chemotherapy and this was significantly longer than the median 46.0 months in patients assigned to the chemotherapy-only arm, with a hazard ratio (HR) for death of 0.75.
The corresponding median progression-free survival (PFS) durations were 18.4 and 14.0 months, with a significant HR for progression or death of 0.66.
The researchers also assessed survival outcomes among patients who were both assigned to and received surgery, with median OS and PFS of 55.5 and 18.5 months, respectively.
And these median survival durations increased further when considering only the cytoreductive surgery patients who achieved complete macroscopic resection, with a median OS of 61.9 months versus 27.7 months for those with incomplete resection.
“[T]he number of patients in whom complete resection was achieved was high; therefore, many patients were not exposed to a surgical burden unnecessarily without having any potential benefit, and the power of the trial was not diluted because of a large proportion of patients who did not undergo successful surgery”, write Philipp Harter et al.
They therefore suggest that patients meeting the AGO criteria “could receive counseling about the options for cytoreductive surgery in centers of gynecologic oncology that have experience in surgery for relapsed ovarian cancer.”
“In contrast, patients who have a high probability of incomplete resection on the basis of disease or clinical characteristics should not be exposed to a potentially harmful surgical treatment”, the researchers advise.
The investigators add that their findings “cannot be extrapolated to interval debulking after chemotherapy or to the treatment of relapse after later lines of treatment. These scenarios deserve further study that should also focus on the potential interaction of surgery with new drugs such as PARP inhibitors or further targeted therapies.”
Discussing the findings in a linked commentary, Ginger Gardner and Dennis Chi, both based at Memorial Sloan Kettering Cancer Center in New York, USA, observe that a substantial number of the DESKTOP III participants required bowel resection, diaphragm surgery, splenectomy or partial hepatectomy.
“[T]hese surgeries underscore the importance of both the surgical volume and the skill needed to successfully perform secondary cytoreductive surgery”, they write.
The commentators suggest that the conflicting findings of the GOG-0213 trial, which did not find a survival benefit with secondary cytoreductive surgery, may be due to the participants being chosen only on the basis of being candidates for gross resection rather than likelihood of complete resection, or the lack of prespecified surgical quality controls.
Ginger Gardner and Dennis Chi conclude: “The DESKTOP III trial showed the benefit of secondary cytoreductive surgery regardless of previous antiangiogenic therapy, and now the growing use of [PARP] inhibitors in combination with secondary cytoreductive surgery deserves further study.”
References
Harter P, Sehouli J, Vergote I, et al. Randomized trial of cytoreductive surgery for relapsed ovarian cancer. N Engl J Med; Advance online publication 2 December 2021. DOI: 10.1056/NEJMoa2103294
Gardner GJ, Chi DS. Recurrent ovarian cancer – sculpting a promising future with surgery. N Engl J Med; Advance online publication 2 December 2021. DOI: 10.1056/NEJMe2116353
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