Asian subgroup analysis in global POLAR program of calmangafodipir on top of mFOLFOX6 for the prevention of CIPN

Abstract

Background Calmangafodipir (CaM) is a superoxide dismutase mimetic and iron chelator and expected, based on its mechanism, to prevent chemotherapy induced peripheral neuropathy (CIPN). The global POLAR program was conducted to evaluate the efficacy in prevention of CIPN in colorectal cancer (CRC) patients treated with oxaliplatin. In the readout of the POLAR program, the primary endpoint was not met (ESMO-GI 2021). Here we report the results of subgroup analysis of the Asian population in the POLAR program.

Methods The POLAR program consisted of two phase 3, global, placebo-controlled trials with CaM to prevent CIPN: POLAR-A in CRC patients who were treated with adjuvant mFOLFOX6 and; POLAR-M in patients with metastatic CRC received first-line mFOLFOX6. The primary endpoint was a proportion of patients scoring 3 or 4 in at least 1 of the first 4 items of the FACT/GOG-NTX-13 questionnaire, assessed 9 months after the first dose of investigational drug. Because of early study completions due to the safety reason, the statistical analysis was conducted for the pooled (POLAR-A and -M) modified intention-to-treat population. For the Asian patients, subgroup analyses of the primary endpoint and PK profile were conducted.

Results In POLAR-A, RR of patient-reported CIPN vs placebo in the Asian population (n=38) was 1.34 (p=0.39), while CaM statistically significantly worsen CIPN in the non-Asian population (n=82) with an increased RR of 1.61 (p=0.039). In contrast, the RR in POLAR-M was 0.89 (p=0.78) in the non-Asian (n=26) and 1.30 (p=0.48) in the Asian (n=29), respectively. The safety profile was similar between the non-Asian and the Asian population. Combined use with FOLFOX potentially caused difference in PK profile of CaM between the Asian and non-Asian population.

Conclusion Between the Asian and the non-Asian population, there were differences in outcome of patient reported CIPN and PK profile in patients who received CaM combined with oxaliplatin.