Phase III Randomized Trial of Maintenance Taxanes Versus Surveillance in Women With Advanced Ovarian/Tubal/Peritoneal Cancer: A Gynecologic Oncology Group 0212:NRG Oncology Study

OS Not Improved, Modest PFS Benefit Noted Following Chemo Maintenance in Newly Diagnosed Advanced Ovarian Cancer

Patients with advanced newly diagnosed ovarian, tubal, or peritoneal cancer did not derive further survival benefit from maintenance chemotherapy, although a modest improvement in progression-free survival was observed compared with surveillance. Although a slight improvement in progression-free survival (PFS) was observed, investigators noted that maintenance chemotherapy did not yield an improvement in overall survival (OS) vs surveillance in patients with newly diagnosed advanced ovarian, tubal, or peritoneal cancer, according to findings from the phase 3 NRG GOG-0212 (NCT00108745) study published in the Journal of Clinical Oncology. Investigators reported that at the fourth scheduled interim analysis, the 2 taxane regimens included in the study passed the futility boundary for OS. A total of 653 deaths took place at a median follow-up of 8.1 years, none of which were related to the treatment regimens. Median OS for the surveillance, paclitaxel, and paclitaxel/poliglumex groups was 58.3 months, 56.8 months, and 60.0 months, respectively. Compared with surveillance, hazard ratios for death were 1.091 (95% CI, 0.911-1.31; P = .343) and 1.033 (95% CI, 0.862-1.24; P = .725) in the paclitaxel and paclitaxel/poliglumex arms, respectively. The patient population included those with stage III or IV disease and allowed for all epithelial types of ovarian cancer with the exception of tumors with low malignant potential and mixed tumors with a sarcomatous component. Treatment via primary surgery or neoadjuvant chemotherapy was allowed so long as patients underwent interval surgical debulking with platinum/taxane chemotherapy for a minimum of 1 cycle but no more than 6. A minimum of 2 cycles of chemotherapy following interval surgery was required. Additionally, patients needed to have completed a minimum of 5 cycles of platinum-based and paclitaxel- or docetaxel-based chemotherapy. To enroll on the study, patients were also required to have a GOG performance status of 0 to 2 and adequate bone marrow, renal, hepatic, and neurologic function. Previous treatment with bevacizumab (Avastin) was not allowed. Those who enrolled on the open-label study were randomized 1:1:1 to receive surveillance, 135 mg/m2 of paclitaxel once every 28 days for 12 cycles, or 135 mg/m2 of paclitaxel/poliglumex once every 28 days for 12 cycles. Depending on the presence of hematologic adverse effects (AEs), doses could be reduced to 100 mg/m2 in the paclitaxel arm and 80 mg/m2 in the paclitaxel/poliglumex arm. The trial’s primary end point was OS, with a secondary end point of PFS. A total of 1157 patients enrolled on the study. Across the paclitaxel/poliglumex, paclitaxel, and surveillance groups, 1.8%, 3.4%, and 3.6% of patients, respectively, were ineligible for participation. Moreover, 4% of patients withdrew consent for or were lost to follow-up. Additional findings from the study indicated that the median PFS in the surveillance, paclitaxel, and paclitaxel/poliglumex groups, respectively, were 13.4 months, 18.9 months, 16.3 months. Grade 3 or higher AEs in the paclitaxel/poliglumex, paclitaxel, and surveillance groups, respectively, included neutropenia (21.6% vs 16.6% vs 0.5%; P <.01); sensory neuropathy (10.0% vs 5.4% vs 0.8%; P <.001); hypokalemia (2.4% vs 0.5% vs 0.0%; P = .001); and joint, bone, and muscle pain (8.2% vs 4.8% vs 2.9%; P = .004).