Treating advanced ovarian cancer by beginning with neoadjuvant chemotherapy (NAC) may lead to decreased complications and less invasiveness compared with the standard of care, according to a presentation Sunday at the Gynecologic Cancer Oral Abstract Session.
Takashi Onda, MD, PhD, of Kitasato University School of Medicine, Japan, presented the safety results of Japan Clinical Oncology Group Study JCOG0602, a phase III study comparing the invasiveness of upfront debulking surgery and NAC for stage III/IV ovarian, tubal, and peritoneal cancers (Abstract 5508). The survival analysis for JCOG0602 will be conducted in 2017.
|Dr. Takashi Onda|
“Treatment starting with neoadjuvant chemotherapy is less invasive than the standard treatment for advanced ovarian cancer,” Dr. Onda said. “If noninferiority of survival is confirmed in the efficacy analysis to be conducted in 2017, NAC will be the new standard treatment for advanced ovarian cancer.”
Standard of care for ovarian cancer includes primary surgical staging or debulking followed by intravenous paclitaxel and carboplatin chemotherapy, and, for patients with stage III disease who are optimally debulked (defined as 1 cm or less residual disease), intravenous/intraperitoneal paclitaxel and intraperitoneal cisplatin chemotherapy.
Dr. Onda explained that two previous studies demonstrated noninferior survival of patients treated with NAC followed by interval debulking surgery (IDS), compared with standard treatment for ovarian cancer. The invasiveness of this approach has not yet been fully analyzed, he said, and one of the objectives of JCOG0602 was to demonstrate the reduced invasiveness of the treatment, in addition to noninferior survival. Another objective was to demonstrate the accuracy of preoperative clinical staging.
Patients in this multicenter study were randomly assigned to standard care (eight cycles of paclitaxel and carboplatin followed by primary debulking surgery [PDS]) or to four cycles of paclitaxel and carboplatin followed by IDS followed by four additional cycles of paclitaxel and carboplatin. In the standard-care arm, IDS was optional for patients who underwent suboptimal PDS. The safety endpoints included: the number of surgeries and operation times; the amount of blood loss and need for blood, plasma, or albumin transfusion; and the incidence of treatment-related adverse events.
Of the 301 patients enrolled between November 2006 and October 2011, 149 were assigned to the standard arm and 152 to the NAC arm. In the standard arm, 147 patients underwent PDS and 48 subsequently underwent IDS. In the NAC arm, 131 underwent IDS.
Operation time for IDS in the NAC arm was longer than operation time for PDS in the standard-care arm, and the standard-care arm required more surgeries, leading to longer total operation time (p < 0.001). Pelvic and para-aortic lymphadenectomy were more frequently performed in the NAC arm (p < 0.001), but the frequency of bowel or organ resection was lower in the NAC arm (p = 0.012). Blood, plasma, and albumin transfusions were less frequent in the NAC arm (p < 0.001). In addition, postoperative adverse events were less frequently observed in the NAC arm.
The paper’s Discussant, Dennis S. Chi, MD, of Memorial Sloan Kettering Cancer Center, noted that JCOG0602 has several weaknesses, including low rates of optimal debulking (37%) and complete gross resection (12%) in the standard-care arm. He said the overall survival and progression-free survival data for the study are immature, and these will be key endpoints for the planned efficacy analysis in 2017.
Dr. Chi said prospective, randomized trials comparing these two approaches in specialized centers are planned. The upcoming international and U.S. TRUST studies will have accrual goals of 800 patients each.