Expert Commentary

Should secondary cytoreduction be performed for platinum-sensitive recurrent ovarian cancer?

OBG Manag. 2020 January;32(1):48-50

Such practice should be questioned, according to authors of a phase 3 randomized, controlled trial. In the study, 485 patients with platinum-sensitive recurrent resectable disease who had received 1 previous therapy and had a 6-month or more platinum-free interval (an interval during which no platinum-based chemotherapy was used) were randomly assigned to receive platinum-based chemotherapy or to undergo surgical cytoreduction followed by platinum-based chemotherapy. There were no statistical differences in overall survival, with a trend favoring nonsurgical patients, or progression-free survival, with a trend favoring surgical patients. However, we would recommend using caution in applying the study data to patients with different platinum-free intervals or low-volume disease limited to the pelvis.

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References

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7-34.
Parmar MK, Ledermann JA, Colombo N, et al. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003;361:2099-2106.
International Collaborative Ovarian Neoplasm Group. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet. 2002;360:505-515.
Mullen MM, Kuroki LM, Thaker PH. Novel treatment options in platinum-sensitive recurrent ovarian cancer: a review. Gynecol Oncol. 2019;152:416-425.
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: ovarian cancer. November 26, 2019. https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf. Accessed December 18, 2019.
Cass I, Baldwin RL, Varkey T, et al. Improved survival in women with BRCA-associated ovarian carcinoma. Cancer. 2003;97:2187-2195.
Gallagher DJ, Konner JA, Bell-McGuinn KM, et al. Survival in epithelial ovarian cancer: a multivariate analysis incorporating BRCA mutation status and platinum sensitivity. Ann Oncol. 2011;22:1127-1132.
Sun C, Li N, Ding D, et al. The role of BRCA status on the prognosis of patients with epithelial ovarian cancer: a systematic review of the literature with a meta-analysis. PLoS One. 2014;9:e95285.
Coleman RL, Brady MF, Herzog TJ, et al. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017;18:779-791.
Coleman RL, Spirtos NM, Enserro D, et al. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019;381:1929-1939.
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Coleman RL, Spirtos NM, Enserro D, et al. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019;381:1929-1939.

EXPERT COMMENTARY

Ovarian cancer represents the most lethal gynecologic cancer, with an estimated 14,000 deaths in 2019.¹ While the incidence of this disease is low in comparison to uterine cancer, the advanced stage at diagnosis portends poor prognosis. While stage is an independent risk factor for death, it is also a risk for recurrence, with more than 80% of women developing recurrent disease.^2-4 Secondary cytoreduction remains an option for patients in which disease recurs; up until now this management option was driven by retrospective data.⁵

Details of the study

Coleman and colleagues conducted the Gynecologic Oncology Group (GOG) 0213 trial—a phase 3, multicenter, randomized clinical trial that included 485 women with recurrent ovarian cancer. The surgical objective of the trial was to determine whether secondary cytoreduction in operable, platinum-sensitive (PS) patients improved overall survival (OS).

Patients were eligible to participate in the surgical portion of the trial if they had PS measurable disease and had the intention to achieve complete gross resection. Women with ascites, evidence of extraabdominal disease, and “diffuse carcinomatosis” were excluded. The primary and secondary end points were OS and progression-free survival (PFS), respectively.

Results. There were no statistical differences between the surgery and no surgery groups with regard to median OS (50.6 months vs 64.7 months, respectively; hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.97–1.72) or median PFS (18.9 months vs 16.2 months; HR, 0.82; 95% CI, 0.66 to 1.01). When comparing patients in which complete gross resection was achieved (150 patients vs 245 who did not receive surgery), there was only a statistical difference in PFS in favor of the surgical group (22.4 months vs 16.2 months; HR, 0.62; 95% CI, 0.48–0.80).

Of note, 67% of the patients who received surgery (63% intention-to-treat) were debulked to complete gross resection. There were 33% more patients with extraabdominal disease (10% vs 7% of total patients in each group) and 15% more patients with upper abdominal disease (40% vs 33% of total patients in each group) included in the surgical group. Finally, the median time to chemotherapy was 40 days in the surgery group versus 7 days in the no surgery group.

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Should secondary cytoreduction be performed for platinum-sensitive recurrent ovarian cancer?

References

Details of the study

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