Abstract PO3-12-11: A phase-3 randomized controlled study to evaluate the role of hydroxyprogesterone in prevention of chemotherapy induced neurotoxicity in women with breast cancer

Abstract Introduction Chemotherapy induced peripheral neuropathy (CIPN) is seen in 60% breast cancer patients who receive paclitaxel-based chemotherapy with no conclusively known pathophysiology. Hydroxyprogesterone is known to have neuroprotective and neuro-regenerative potential. We conducted a randomized controlled trial assessing the role of hydroxyprogesterone in reducing the incidence and severity of CIPN. Methodology Histologically proven, post-menopausal, non-metastatic breast cancer patients without pre-existing neuropathy, planned to receive paclitaxel (with or without trastuzumab) in the adjuvant or neoadjuvant setting were screened and consented. They were randomized to receive depot hydroxyprogesterone injection 500 mg followed by 250 mg injection every 2 weekly (trial arm) versus 1 ampoule (2 ml) of vitamin-B complex (B1-100mg, B6-100mg and B12-1000µg) injection every 2 weekly (control arm) during the entire course of paclitaxel-based chemotherapy. The primary end point was cumulative incidence of grade II-IV CIPN, at the last cycle of chemotherapy as assessed by CTCAE-V4. Secondary end point was EORTC-QLQ-CIPN20 assessment 8 weeks after last cycle of chemotherapy. Patients were stratified for stage, diabetes mellitus, and frequency of paclitaxel administration. Sample size was calculated for a 20% reduction in CIPN from 60% with α-0.05 and power of 80%, for 2-sided significance of p-0.05, with a drop-out rate of 10%. Results A total of 240 patients were randomized between November 2015 and February 2023- 120 each on the trial and control arm. The median age was 54 (43-73) and 55 (43-74) years; 35% and 31.7% patients were early breast cancer (cT1-2, N0-1) in the trial and control arms respectively. The median pT size was 2.6 cm and 65% patients were node positive overall. The incidence of grade II-IV CIPN (motor and/or sensory) at the end of chemotherapy was 55.9% and 56.8% in the trial and control arms respectively (p=0.90, 95%CI-0.12-0.13). Overall, chemotherapy related adverse events (CTCAE-V4) were seen in 41.39 and 39.9% in trial and control arms respectively. The average EORTC-QLQ-CIPN20 score at 8 weeks after last cycle of chemotherapy for motor neuropathy was 11.18 (0-70) and 13.53 (0-74), for sensory neuropathy was 8.51 (0-76) and 9.27 (0-81) and that for autonomic neuropathy was 4.94 (0-67) and 4.65 (0-67) in the trial and control arms respectively (p=NS). Conclusion Hydroxyprogesterone did not reduce the incidence of paclitaxel related CIPN when assessed immediately post-chemotherapy. The absolute incidence of CIPN (any grade) was 61% in our study which is like that reported in literature. Long term follow-up of these patients will assess the recovery of CIPN and long-term impact of the study interventions on CIPN. The study was approved by Institutional Review Board and Drug Controller General of India (CTRI/2015/11/006381). Citation Format: Rajendra Badwe, Shalaka Joshi, Rohini Hawaldar, Tejal Panhale, Nita Nair, Sandesh Sawant, Vaibhav Vanmali, Mitchelle Engineer, Anuradha Daptardar, Vani Parmar, Seema Gulia, Sudeep Gupta. A phase-3 randomized controlled study to evaluate the role of hydroxyprogesterone in prevention of chemotherapy induced neurotoxicity in women with breast cancer [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 PO3-12-11.