Secondary Cytoreduction Fails to Improve OS in Phase III Ovarian Cancer Study

Robert L. Coleman, MD

Robert L. Coleman, MD

Overall survival was not improved with secondary cytoreduction followed by chemotherapy compared with chemotherapy alone in the phase III GOG-0213 trial, which missed its primary endpoint.

Results showed that the median overall survival (OS) was 50.6 months in the secondary cytoreduction group compared with 64.7 months in the chemotherapy-alone group (HR, 1.29; 95% CI, 0.97-1.72;P= .08).

Additionally, the median progression-free survival (PFS) was 18.9 months and 16.2 months with secondary cytoreduction/chemotherapy and chemotherapy alone, respectively (HR, 0.82; 95% CI, 0.66-1.01). The 3-year OS rate was 67% for those on the surgery arm and 74% for patients who only received chemotherapy.

“Surgical cytoreduction is recognized as a key component of frontline treatment for primary ovarian cancer, but its role in recurrent disease, while touted as beneficial, had not been formally tested,” lead investigator Robert L. Coleman, MD, professor of gynecologic oncology and reproductive medicine, The University of Texas MD Anderson Cancer Center, stated in a press release. “This research is the first randomized clinical trial conducted in this setting and shows that secondary surgery does not benefit these patients.”

Currently, NCCN guidelines state that secondary cytoreduction is a treatment option for patients who have been treatment free for ≥6 months after achieving complete remission from prior chemotherapy.

The international, multicenter, GOG-0213 trial had 2 objectives: to evaluate the addition of bevacizumab (Avastin) to chemotherapy, followed by maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer; and to compare the benefit of secondary cytoreduction/chemotherapy with no surgery/chemotherapy in the same patient population.

Results of the first objective showed that the addition of bevacizumab improved median OS in patients, but it was not statistically significant in the intent-to-treat population.³

For the second objective, 485 female patients with platinum-sensitive, epithelial recurrent ovarian, primary peritoneal, or fallopian tube cancer who had a complete clinical response to ≥3 cycles of primary platinum-based chemotherapy and a normal serum CA-125 value were randomized to undergo secondary surgical cytoreduction followed by platinum-based chemotherapy (n = 240) or chemotherapy alone (n = 245).

To be eligible for enrollment, patients had to be ≥18 years old; have platinum-sensitive and investigator-determined disease; adequate renal, hepatic, and bone marrow function; a Gynecologic Oncology Group performance score of 0 to 2; had a disease-free survival of ≥6 months after infusion of their last cycle of chemotherapy; and a minimum of 6 months since last infusion if they received maintenance chemotherapy. For patients who had bevacizumab or hormonal maintenance treatment, a treatment-free window of ≥4 weeks was required. Those who were not medically fit for surgery or had diffuse carcinomatosis, ascites, or extra-abdominal disease were excluded.

Adjuvant therapy with paclitaxel/carboplatin or gemcitabine/carboplatin and the use of bevacizumab were used by choice of the investigator. Platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance was given to 84% of patients overall, which was equally distributed between the 2 groups.

A total 11% (n = 55) of patients had previous bevacizumab exposure, and the median platinum-free interval was 20.4 months in the surgery group and 18.8 months in the chemotherapy-alone group. Regarding the median OS, the investigators noted that the adjustment for platinum-free interval and chemotherapy choice did not alter the effect on survival.

The primary endpoint was OS; investigator-assessed PFS was a secondary endpoint.

At a median follow-up of 48.1 months, results also showed that the complete tumor resection rate was 67% in the secondary cytoreduction arm. The 3-year PFS rate was 29% (95% CI, 22%-35%) with secondary cytoreduction and 20% (95% CI, 15%-26%) with chemotherapy alone.

When comparing patients whose tumors were completely resected (n = 150) with those whose disease could not be completely resected (n = 89), surgery was associated with longer OS (HR, 0.61; 95% CI, 0.40-0.93) and PFS (HR, 0.51; 95% CI, 0.36-0.71). However, a comparison of the complete resection group with the no-surgery group showed that secondary cytoreduction led to an improvement in PFS (HR, 0.62; 95% CI, 0.48-0.80) but not OS (HR, 1.03; 95% CI, 0.74-1.46).

Patients who underwent secondary cytoreduction reported a significant decrease in quality of life and physical function and an increase in surgery-related symptoms immediately after surgery. However, there was no significant difference in patient-reported outcomes between the 2 treatment arms after patients in the cytoreduction arm recovered from surgery.