Time Between Neoadjuvant and Adjuvant Chemo Impacts OS in Ovarian Cancer

Author(s):

Patients with ovarian cancer who begin postoperative adjuvant chemotherapy within 42 days of ending neoadjuvant chemotherapy have superior survival compared to those who initiate therapy after that point.

Investigators in South Korea conducted a retrospective analysis of 194 women with pathologically confirmed epithelial ovarian cancer who received neoadjuvant chemotherapy at Yonsei Cancer Hospital in Seoul from 2006 to 2016. In the multivariate analysis, a longer interval to treatment initiation was associated with significantly poorer progression-free survival (PFS; hazard ratio [HR], 1.41; 95% CI, 0.98-2.03) and overall survival (OS; HR, 2.03; 95% CI, 1.16-3.54).

The time interval was defined as the period from the completion of neoadjuvant chemotherapy, spanning interval debulking surgery (IDS), to the initiation of postoperative adjuvant chemotherapy.

“Our results demonstrate that a significant correlation may exist between survival outcomes and the time intervals between the completion of neoadjuvant chemotherapy and initiation of postoperative adjuvant chemotherapy, and that a delay in postoperative adjuvant chemotherapy initiation beyond 42 days after neoadjuvant chemotherapy may lead to worse survival outcomes,” corresponding author Jung-Yun Lee, MD, and coinvestigators wrote.

“Further studies are warranted to validate our findings and to provide additional information on the relationships between neoadjuvant chemotherapy, the initiation of postoperative adjuvant chemotherapy, and the survival outcomes of the patients,” continued Lee et al.

All patients were confirmed to have stage III or IV disease prior to starting chemotherapy. The median age was 57 (range, 31-78) years, and 178 (91.8%) had serous histology.

Eighty-two patients (42.3%) underwent radical surgery, including 30 (15.5%) who underwent bowel surgery. In 86 patients (44.3%), there was no gross residual tumor present after IDS.

All patients received platinum-based combination chemotherapy. A total of 155 patients (79.6%) received paclitaxel plus carboplatin, and the median number of cycles of total chemotherapy was 8 (range, 4-12).

About half of patients (n = 103; 53.1%) began postoperative treatment within the 42-day interval and 91 (46.9%) initiated after 42 days. There were no significant differences in the patient characteristics, such as age, body mass index, ASA score, baseline CA-125, FIGO stage, histologic types, CA-125 before IDS, surgery extent, residual disease, complication rate, chemotherapy regimens, and cycles of total chemotherapy between the 2 groups.

FIGO stage (HR, 1.66; 95% CI, 1.03-2.67), non—high-grade serous carcinoma histology (HR, 2.13; 95% CI, 1.11-4.08), and any residual disease (HR, 1.71; 95% CI, 1.17–2.49) were independent prognostic factors associated with a higher risk of progression. For OS, multivariate analysis showed that a longer time interval was an independent prognostic factor in all patients (HR, 2.03; 95% CI, 1.16-3.54). Furthermore, non–high-grade serous carcinoma histology (HR, 3.79; 95% CI, 1.67-8.62) and any residual disease (HR, 2.26; 95% CI, 1.21-4.24) were significantly associated with a higher risk of death.

The patients were also categorized based on the residual diseases (R0, R0-0.5 cm, R0.5-1.0 cm, R >1.0 cm) to evaluate the presence of a linear trend. Residual disease was found to be an independent prognostic factor associated with higher risks for progression and death.

Investigators separated patients into quartiles based on the time intervals (≤37, 38-42, 43-50, and >50 days) to evaluate the presence of a linear trend. Patients with longer time intervals were found to have higher risks for recurrence (P for trend = .006) and death and (P for trend <.001). Patients in the highest quartile (>50 days) had the highest risks of recurrence (HR, 1.93; 95% CI, 1.16-3.20) and death (HR, 2.06; 95% CI, 1.05-4.02), as compared with patients in the lowest quartile (≤37 days).

Lee YJ, Chung YS, Lee J, et al. Impact of the time interval from completion of neoadjuvant chemotherapy to initiation of postoperative adjuvant chemotherapy on the survival of patients with advanced ovarian cancer [published online November 21, 2017]. Gynecol Oncol doi: 10.1016/j.ygyno.2017.11.023.