In a post hoc analysis from the ICON8 trial reported in The Lancet Oncology, Morgan et al found evidence indicating that the evaluation of response to platinum-based neoadjuvant therapy in women with ovarian carcinoma using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, should not be used alone to determine whether delaying primary surgery will be beneficial.
“The RECIST-defined radiological response rate was lower than that frequently quoted to patients in the clinic. RECIST and GCIG CA125 responses to neoadjuvant chemotherapy for epithelial ovarian cancer should not be used as individual predictive markers to stratify patients who are likely to benefit from delayed primary surgery, but instead used in conjunction with the patient’s clinical capacity to undergo cytoreductive surgery. A patient should not be denied surgery based solely on the lack of a RECIST or GCIG CA125 response.”— Morgan et al
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Study Details
The ICON8 trial included 1,566 women with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage IC to IV cancer of the ovary, fallopian tube, or primary peritoneum. Patients were randomly assigned to receive one of three neoadjuvant carboplatin/paclitaxel regimens. The previously reported intention-to-treat primary progression-free survival analysis showed no significant difference between standard 3-weekly carboplatin plus paclitaxel vs either 3-weekly or weekly carboplatin plus weekly paclitaxel.
The current analysis included 779 patients with predominantly FIGO stage III to IV high-grade serous carcinoma who were planned to receive delayed primary surgery and had RECIST version 1.1–evaluable disease at trial entry or Gynecologic Cancer InterGroup CA-125 (GCIG CA-125)–evaluable disease at time of diagnosis. Progression-free survival was assessed in a landmark analysis and was defined as the time between date of presurgical planning radiologic tumor assessment and date of investigator-assessed clinical or radiologic progression or death.
Key Findings
Median follow-up was 29.5 months (interquartile range = 15.6–54.3 months) in women who received neoadjuvant chemotherapy followed by delayed primary surgery. Among 564 women with RECIST-evaluable disease, 348 (62%) had a complete or partial response. Among 727 women with CA-125–evaluable disease, 610 (84%) had a CA-125 response. Among 534 women with both RECIST and CA-125 data, RECIST stable or progressive disease was found in 148 (33%) of 453 patients with a CA-125 response.
Median progression-free survival was 14.4 months (95% confidence interval [CI] = 9.2–28.0 months) among patients with RECIST complete or partial response and 13.3 months (95% CI = 8.1-20.1 months) among those with RECIST stable disease. In analysis excluding the 13% of women who did not undergo surgery, median progression-free survival was 15.0 months and 14.0 months.
Median progression-free survival was 13.8 months (95% CI = 8.8–23.4 months) among women with a CA-125 response and 9.7 months (95% CI = 5.8–14.5 months) among those without a CA-125 response. In analysis excluding the 15% of women who did not undergo surgery, median progression-free survival was 14.2 months and 10.5 months.
Complete cytoreduction was achieved in 187 (56%) of 335 women with a RECIST complete or partial response and 73 (42%) of 172 with RECIST stable disease. Complete cytoreduction was achieved in 290 (50%) of 576 women with CA125 response and 30 (30%) of 101 without a CA-125 response.
The investigators concluded, “The RECIST-defined radiological response rate was lower than that frequently quoted to patients in the clinic. RECIST and GCIG CA125 responses to neoadjuvant chemotherapy for epithelial ovarian cancer should not be used as individual predictive markers to stratify patients who are likely to benefit from delayed primary surgery, but instead used in conjunction with the patient’s clinical capacity to undergo cytoreductive surgery. A patient should not be denied surgery based solely on the lack of a RECIST or GCIG CA125 response.”
Andrew R. Clamp, PhD, of The Christie NHS Foundation Trust and The University of Manchester, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Cancer Research UK, UK Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, and Cancer Australia. For full disclosures of the study authors, visit thelancet.com.
