Lack of reliability of CA125 response criteria with anti‐VEGF molecularly targeted therapy

Abstract

BACKGROUNDCA125 is an accepted indicator of epithelial ovarian cancer (EOC) response and is used to monitor patients treated with cytotoxic chemotherapy. It is uncertain how CA125 is affected by molecularly targeted drugs. In this pilot study, the authors analyzed the utility of CA125 to predict disease behavior in patients who were receiving sorafenib, a Raf‐kinase/VEGFR2 inhibitor, and bevacizumab, an anti‐VEGF monoclonal antibody.METHODSFifteen of 42 patients had recurrent EOC. Patients received sorafenib 200 mg orally twice daily or D1‐5 of 7 and bevacizumab 5 mg/kg to 10 mg/kg intravenously every 2 weeks for 28‐day cycles. Computed tomography (CT) scans were performed every 2 cycles for restaging, and CA125 was measured monthly. CA125 concentrations were retrospectively analyzed as a function of clinical behavior.RESULTSFourteen of 15 patients had abnormal CA125 concentrations at study entry (median 1056 U/mL; range, 67 U/mL to 9813 U/mL). Seven (47%) patients had partial response by imaging criteria. Five of these 7 patients had partial response by CA125 criteria (71% sensitivity). Eight (53%) patients would have had partial responses if CA125 criteria were used; only 5 were confirmed by CT (63 % specificity). Imaging and CA125 criteria combined yielded a higher total response rate of 10 of 15 (67%). Three patients with objective partial response by imaging lasting >20, >22, and >24 cycles would have terminated treatment prematurely if CA125 had been used.CONCLUSIONSCA125 changes may not correspond to imaging response criteria for EOC patients who are receiving sorafenib and bevacizumab. Caution is recommended when using CA125 as a response criterion of molecularly targeted agents until prospective studies validate CA125 changes with objective imaging response results. Cancer 2008. © 2008 American Cancer Society.

Recurrence patterns after extended treatment with bevacizumab for ovarian, fallopian tube, and primary peritoneal cancers

“…Limitations regarding the use of CA125 levels to follow disease during treatment with bevacizumab have also recently been reported. Our findings regarding the limitations of CA-125 are consistent with a prior study of 15 recurrent ovarian cancer patients treated with sorafenib and bevacizumab, in which the authors reported that CA-125 changes did not agree with objective imaging (67% concordance) in predicting disease behavior [28]. In retrospective analysis of 62 patients with persistent or recurrent ovarian or peritoneal cancer treated with bevacizumab (Gynecologic Oncology Group protocol 170-D), Randall and colleagues observed that CA-125 and RECIST-defined progression correlated in most cases (31% and 21%, respectively), but 12.9% of those with CA-125 defined progression remained progression-free according to RECIST criteria for at least 5.7 months [29].…”

Predictors of the efficacy of FOLFIRI plus bevacizumab as second-line treatment in metastatic colorectal cancer patients

“…12 Azad et al hypothesized that molecularly targeted agents might modulate CA125 production and secretion, and examined its reliability. 13 Their study was the fi rst analysis of prospectively obtained CA125 samples with concurrent imaging in a trial of molecularly targeted agents using concomitant sorafenib (a Raf-kinase/VEGF receptor 2 inhibitor) and BV (an anti-VEGF monoclonal antibody) in epithelial ovarian cancer. The results showed that the RRs were similar between the CA125 criteria and RECIST imaging criteria; however, CA125 changes did not appear to correlate with earlier diagnosis of disease progression than that of RECIST imaging.…”

Predictive value of serum CA-125 levels in patients with persistent or recurrent epithelial ovarian cancer or peritoneal cancer treated with bevacizumab on a Gynecologic Oncology Group phase II trial

“…This finding was observed in a previously-published report of 15 patients treated with bevacizumab in combination with sorafenib, where CA-125-defined progression preceded RECIST-defined progression in 3 patients. 14 Our findings are hypothesis-generating and might have important implications for the design of future clinical trials and the management of patients on bevacizumab or other anti-angiogenic therapy.…”