medwireNews: Phase III trial investigators challenge the use of secondary surgical cytoreduction for recurrent platinum-sensitive ovarian cancer amenable to surgery, finding no benefit over chemotherapy alone.
The team writes in The New England Journal of Medicine that combining the procedure with platinum-based chemotherapy is “widely practiced” and “appears to be feasible, with acceptable postoperative morbidity”.
However, the use of secondary surgical cytoreduction alongside chemotherapy did not significantly improve overall survival (OS) compared with chemotherapy alone, report Robert Coleman, from the University of Texas MD Anderson Cancer Center in Houston, USA, and co-authors.
The study included 485 patients with resectable epithelial ovarian, primary peritoneal or fallopian tube cancer who had achieved a complete clinical response after receiving three or more cycles of platinum-based chemotherapy more than 6 months earlier and had not received any other chemotherapy in the intervening months.
Complete gross resection was achieved in 67% of the 240 patients who were randomly assigned to receive secondary cytoreduction before receipt of six cycles of carboplatin–gemcitabine or carboplatin–paclitaxel with or without bevacizumab. In all, 84% of patients received chemotherapy plus bevacizumab followed by bevacizumab maintenance, the researchers say.
At a median of 48.1 months of follow-up, median OS was 50.6 months for use of secondary cytoreduction with chemotherapy versus 64.7 months for chemotherapy alone, giving a nonsignificant hazard ratio (HR) for death of 1.29 in favour of no surgery.
Progression-free survival (PFS) was also statistically comparable, with corresponding median durations of 18.9 and 16.2 months. Three-year PFS was achieved by 29% of the secondary cytoreduction group versus 20% of those who received only chemotherapy.
In the secondary surgical cytoreduction arm, patients with complete gross resection had significantly better OS than those whose resection was incomplete (median 56.0 vs 37.8 months, HR=0.61), as well as significantly longer PFS (22.4 vs 13.1 months, HR=0.51).
But when patients with complete resection were compared with the no-surgery arm, there was no significant OS benefit with use of secondary surgical cytoreduction, although there was a significant improvement in PFS (median 22.4 vs 16.2 months, HR=0.62), say Robert Coleman et al.
The researchers observe that the median OS for the study participants was “nearly three times longer than expected” for the trial design.
“The precise reasons for this are unknown but are probably related to improvements in clinical care and the availability of more effective treatments, particularly those in selected populations (e.g., use of PARP inhibitors in patients with tumors with alterations in BRCA1 or BRCA2)”, they hypothesise.
Noting that at least three ongoing phase III trials, including the DESKTOP-III study, are assessing the use of surgery plus chemotherapy versus surgery alone in patients with recurrent ovarian cancer, the team awaits these findings which should “shape the debate on the value or merit of surgery in this patient population.”
Coleman RL, Spirtos NM, Enserro D, et al. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med 2019; 381: 1929–1939. Published online 13 November. DOI: 10.1056/NEJMoa1902626
medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group