ICON8: RECIST, CA125 Response Should Not Solely Guide Surgery Choice

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Post-hoc exploratory analysis of the ICON8 trial indicates that RECIST and cancer antigen (CA)125 responses to neoadjuvant chemotherapy used alone do not indicate whether patients with epithelial ovarian cancer will benefit from delayed primary surgery (DPS). 

When considered alongside results from the CHORUS, EORTC 55971 and JCOG 0602 trials, the ICON8 investigators say their findings “provide robust evidence that women diagnosed with FIGO stage III–IV epithelial ovarian cancer who are treated with platinum-based neoadjuvant chemotherapy should be considered for DPS even if they only have RECIST stable disease.” 

The ICON8 study previously demonstrated that patients with newly diagnosed FIGO stage IC–IIA high-grade serous carcinoma or stage IIB–IV epithelial cancer of the ovary, fallopian tube or primary peritoneum do not derive a significant progression-free survival (PFS) benefit with neoadjuvant treatment given either as weekly dose-dense carboplatin and paclitaxel, or dose-dense paclitaxel plus 3-weekly carboplatin versus a standard 3-weekly regimen of carboplatin and paclitaxel. Nor was there a PFS benefit from use of immediate surgery versus DPS.  

In the exploratory analysis, Andrew Clamp, from The Christie NHS Foundation Trust and University of Manchester in the UK, and co-workers used a landmark method, defining PFS as the time interval from preoperative radiological tumour assessment to clinical or radiological progression or death. 

The investigators followed up 779 women assigned to undergo neoadjuvant chemotherapy followed by DPS for a median 29.5 months. Of the 564 patients with RECIST-evaluable disease, 62% had a complete or partial response and 32% had stable disease, while 6% had progressive disease. 

And 84% of the 727 women who were assessed using Gynecologic Cancer InterGroup CA125 criteria had a positive response.  

Median PFS did not differ between the patients with a complete or partial RECIST response and those with RECIST stable disease, at 14.4 and 13.3 months, respectively.  

Surgical information was available for 95% of patients with RECIST-evaluable disease; when assessing only the 497 patients who underwent DPS, the median PFS values for patients with complete or partial responses versus stable disease were 15.0 and 14.0 months, respectively. 

“It is notable that the survival outcomes determined using a landmark analysis are approximately 2 months shorter than those reported in the intention-to-treat primary efficacy analysis”, the researchers comment in The Lancet Oncology. 

Median PFS was 13.8 months for patients with a CA125 response and 9.7 months for those who did not respond, with corresponding durations of 14.2 and 10.5 months when assessing only women who underwent DPS. 

Complete cytoreduction was achieved in 56% of patients with a RECIST complete or partial response versus 42% of those with stable disease and 48% of those with progressive disease.  

But median PFS correlated with surgical extent, with the best survival found in women who had R0 cytoreductive surgery regardless of RECIST response, the researchers say. 

Complete cytoreduction was achieved in 50% of patients with a CA125 response and 30% of those without, and DPS was more common in women with than without a CA125 response (89 vs 60%). 

“Both response criteria imperfectly predict the ability to achieve complete or optimal cytoreduction at interval surgery—a more robust surrogate for survival, or indeed progression-free survival”, summarise Andrew Clamp and co-workers. 

“We recommend therefore that RECIST and CA125 assessments should not be considered as standalone measures to stratify patients who are likely to benefit from DPS, but instead used in conjunction with the patient’s clinical capacity (eg, performance status and comorbidities) to undergo cytoreductive surgery.” 

Noting that BRCA1/2 status and use of the chemotherapy response score system have evolved since the ICON8 trial was performed, the researchers add: “We recommend that BRCA1/2 mutation status, chemotherapy response score, and the presence or absence of ascites before DPS are collected in appropriate cases to improve clinical usefulness.” 

Reference 

Morgan RD, McNeish IA, Cook AD, et al. Objective responses to first-line neoadjuvant carboplatin–paclitaxel regimens for ovarian, fallopian tube, or primary peritoneal carcinoma (ICON8): post-hoc exploratory analysis of a randomised, phase 3 trial. Lancet Oncol; Advance online publication 22 December 2020. DOI:10.1016/S1470-2045(20)30591-X