Abstract P5-13-10: Elevated plasma IL-8 predicts for reduced outcomes in CCTG MA.38, a phase 2 randomized trial of palbociclib in ER+/HER2- metastatic breast cancer patients
Authors: Polimera Hyma V , Bhatt Dhirisha , Shepherd Lois E , Gelmon Karen , Joy Anil A , Parulekar Wendy R , Joshi Monika , Ali Suhail M , Leitzel Kim , Truica Cristina , Vasekar Monali , Drabick Joseph J , Menon Harry , Shah Neal , Maddukuri Ashok , Moku Prashanth , Halstead E. Scott , McKeone Daniel , Umstead Todd M , Chen BE , Lipton Allan 
Published: March 2022

Abstract
Background: CCTG MA38 (NCT02630693) was a randomized phase II clinical trial that evaluated the efficacy of 2 dose schedules of palbociclib [100mg PO on continuous daily dose (CDD)] compared to 125mg PO daily for 3 weeks on/1 week off (STD) along with physician-choice of endocrine therapy in patients with ER+, HER- metastatic breast cancer (MBC) in the second-line setting. The final analysis indicated that palbociclib had comparable efficacy, safety and QOL for both treatment arms (SABCS 2018, abstr PD1-10). Our lab has reported that IL-8 was highly expressed by primary human breast cancers, and that higher pretreatment plasma IL-8 was significantly correlated with elevated bone resorption in HR+MBC patients (Kamalakar A et al. Bone 61:176-85, 2014). Most recently, our lab has reported that elevated serum IL-8 predicts for significantly reduced OS in 3 large metastatic cohorts of pancreatic (ASCO 2019, abstr 4131), prostate (ASCO 2020, abstr e17565) and breast cancer patients (ASCO 2020, abstr 1067). In this retrospective study, we investigated the prognostic value of pretreatment plasma IL-8 in CCTG MA38. Methods: 123 patients enrolled in MA38 were analyzed in this retrospective biomarker study. Serum IL-8 levels were measured using the ELLA immunoassay platform (ProteinSimple, San Jose, CA). Kaplan-Meier analysis and log-rank test were used to correlate plasma IL-8 levels with OS and progression-free survival (PFS). Results: In the total study cohort, pretreatment plasma IL-8 concentration had a median of 11.10 pg/ml, and 25% and 75% interquartiles of 7.36 and 15.00 pg/ml, respectively. In univariate analysis higher plasma IL-8 was a significant adverse biomarker for reduced PFS as a continuous variable (p = 0.01), at the median cutpoint (HR= 1.55, p=0.042), and in quartile cutpoints (HR=2.28, p=0.03, Q4 vs Q1). For OS, higher plasma IL-8 also trended significant for reduced OS at the median cutpoint (HR= 1.66, p=0.10). In multivariate analysis, higher plasma IL-8 also trended significant for reduced PFS (HR= 1.47, p=0.094). Conclusions: In the CCTG MA.38 trial, higher pre-treatment plasma IL-8 level was associated with reduced PFS, and is therefore an adverse prognostic biomarker for reduced outcome to the CDK 4/6 inhibitor palbociclib. Anti-IL-8 therapy combined with CDK 4/6 inhibitors should be evaluated in future trials to improve outcome in patients with higher circulating IL-8.
Citation Format: Hyma V Polimera, Dhirisha Bhatt, Lois E Shepherd, Karen Gelmon, Anil A Joy, Wendy R Parulekar, Monika Joshi, Suhail M Ali, Kim Leitzel, Cristina Truica, Monali Vasekar, Joseph J Drabick, Harry Menon, Neal Shah, Ashok Maddukuri, Prashanth Moku, E. Scott Halstead, Daniel McKeone, Todd M Umstead, BE Chen, Allan Lipton. Elevated plasma IL-8 predicts for reduced outcomes in CCTG MA.38, a phase 2 randomized trial of palbociclib in ER+/HER2- metastatic breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-10.