Abstract PO3-28-04: Ganglioside-Monosialic Acid for Prevention of Peripheral Neuropathy Induced by nab-Paclitaxel in Breast Cancer Patients (HELEN-004): A Randomized, Double-Blind, Phase II Trial

Abstract Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a dose limiting adverse effect of nab-paclitaxel. Ganglioside-Monosialic Acid (GM1) is an abundant glycosphingolipid in neuronal membranes and studies have shown its potential in preventing CIPN as a neuroprotective factor. This study was conducted to evaluate the effect of GM1 in preventing CIPN induced by nab-paclitaxel in breast cancer patients. Methods This study was a randomized, double-blind, placebo-controlled phase II trial conducted at three hospitals in China (NCT04222790). Female patients 18 to 75 years with early-stage breast cancer who were scheduled to receive nab-paclitaxel containing chemotherapy were randomly assigned to receive GM1 or placebo. Nab- paclitaxel was given 125-150 mg/m2 once per week for 12 cycles or 260 mg/m2 once every 3 weeks for four cycles. GM1 or placebo started one day before chemotherapy and was given once per day for 3 days (day −1, day 1, and day 2). The primary outcome was peripheral neuropathy evaluated by the Functional Assessment of Cancer Treatment Neurotoxicity (FACT-Ntx) subscale at 2 weeks after four cycles of chemotherapy. Other endpoints included peripheral neuropathy evaluated by CTCAE version 4.0, Functional Assessment of Cancer Therapy – General (FACT-G) scores and Functional Assessment of Cancer Therapy – Taxane (FACT-Taxane) scores at 2 weeks after four cycles of chemotherapy. Adverse events were evaluated by CTCAE version 4.0. Additional long-term assessments were performed at 3 months, 6 months, and 1 year after the completion of chemotherapy. All assessments were performed by trained physicians. Results 159 patients were enrolled from April 2020 to June 2021, with 79 patients assigned to the GM1 group and 80 patients to the placebo group. Eight patients in the GM1 group and eight patients in the placebo group did not complete the endpoint assessments. In total, 71 patients in GM1 group and 72 in placebo group were evaluated. Baseline characteristics were generally well balanced between groups. After four cycles of Nab-paclitaxel containing chemotherapy, Patients in the GM1 group reported similar mean FACT-Ntx subscale 36.1 (35.1-37.0) with patients in the placebo group 36.4 (35.3-37.3). Compared with baseline, the mean FACT-Ntx score at two weeks after four cycles of chemotherapy decreased by 7.9 in the GM1 group (p< 0.001) and 7.6 in the placebo group (p< 0.001). The difference between GM1 group and placebo group was not statistically significant (P=0.703). No difference was observed in secondary outcomes except that GM1 group showed lower FACT G scores (61.0, 95% CI, 58.1-63.9) than the control group (67.0, 95% CI, 63.2-70.8) at two weeks after four cycles of chemotherapy, the difference was statistically significant (P=0.014). The main results of primary and secondary outcomes were summarized in Table 1. Random assignment was stratified by age (< 60 or >=60) and BMI ((< 24 or >=24). Subgroup analysis was performed for patients in different age and BMI groups. Overall, patients above 60 years old showed lower FACT-Ntx score at than patients under 60 (34.1 and 36.5, respectively. P=0.056). Overweight patients (BMI >=24) showed similar FACT-Ntx score with patients with BMI smaller than 24 (36.8 and 35.7, respectively. P=0.095). The FACT-Ntx score was not significantly different between the GM1 and placebo group in different age and BMI subgroups. The most common adverse events, including myalgia-arthralgia, nausea, vomit, and diarrhea, were evaluated according to CTCAE version 4.0. Incidence and severity of adverse events were not statistically significantly different between the two groups. Conclusion GM1 did not prevent peripheral neuropathy induced by nab-paclitaxel in breast cancer patients. The effect of GM1 in preventing CIPN is still inconclusive and further studies are needed. Caution in recommending GM1 to prevent CIPN is clearly warranted. Table 1. FACT-Ntx subscale, CTCAE version 4.0, FACT-Taxane and FACT G at 2 weeks after four cycles chemotherapy. a. FACT-Ntx: Functional Assessment of Cancer Treatment- Neurotoxicity; b. CTCAE4.0: Common Terminology Criteria for Adverse Events; c. FACT-Taxane: Functional Assessment of Cancer Treatment – Taxane; d. FACT G: Functional Assessment of Cancer Treatment- General. Citation Format: Zhenduo Lu, Dechuang Jiao, Jianghua Qiao, Hao Zhang, Hao Dai, Xianfu Sun, Min Yan, Yong Zhou, Lianfang Li, Chengzheng Wang, Xiuchun Chen, Zhenzhen Liu. Ganglioside-Monosialic Acid for Prevention of Peripheral Neuropathy Induced by nab-Paclitaxel in Breast Cancer Patients (HELEN-004): A Randomized, Double-Blind, Phase II Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-28-04.