2022-RA-1088-ESGO Chitinase response after 3 cycles of chemotherapy as a promising marker of chemosensitivity an ancillary analysis of the GINECO-ENGOT EWOC-1 trial

Introduction/Background

Older patients with ovarian cancer have poor outcomes; the geriatric vulnerability score (GVS) was validated as a prognostic factor for survival. During aging the circulating Chitinase 3-like-1 (CHI3L1), and its related chitinase enzymatic activity increase, leading to propose them as ‘aging biomarkers’. However, recent data supported the implication of chitinase-like proteins in the proliferation of several cancers. The EWOC-1 trial (NCT02001272) showed a lower efficacy of the carboplatin monotherapy (Cmono) arm compared to carboplatin-paclitaxel (CP) in vulnerable patients; a serum sampling was provided on inclusion, after 3 and 6 courses of chemotherapy for the measurement of chitinase activity in each arm (A: standard CP; B: Cmono; C: 3weeks/4 CP), to identify whether its association with patients’ outcomes and inversely, the differential impact of the distinct treatment regimens on it.

Methodology

Chitinase activity was assessed as previously published. Were analyzed both its absolute value on inclusion (‘chitinase baseline’) and its kinetics after 3 chemotherapy courses (‘chitinase response’).

Results

Serum samples could be retrieved for 46/120 patients on inclusion and 33 after 3 chemotherapy courses. Chitinase baseline median activity (in U/L, IQR) was 1727.9 (1459.3; 1878.3) at inclusion, similar in the 3 arms; no association was shown with any of the geriatric vulnerability parameters, nor the GVS, nor overall survival. Chitinase response was significantly different in the 3 arms, with a median (in U/L, IQR) of -160 (-297; 35.2) in the total cohort, -272 (-376; -122) in arm A, 105 (-109; 221) in arm B and -160 (-663; -109) in arm C, p=0.008. High chitinase response was associated with high CA-125 ELIMination rate constant K (KELIM), a marker of chemosensitivity (Fisher exact test, p=0.042).

Conclusion

Chitinase activity should not be considered, in the context of ovarian cancer as an aging biomarker, but chitinase response appears as a promising marker of chemosensitivity.