Purpose To investigate risk factors for instrumentation failure (IF) in titanium (Ti) mesh reconstruction for thoracic and lumbar tumors. Patients and Methods The clinical data of patients with thoracic or lumbar tumors who received Ti mesh reconstruction via the posterior approach in our hospital from 2013 to 2018 were analyzed retrospectively. The observation indexes included sex, age, BMI, the vertebra resection mode, the number of resected vertebral segments, application of bone cement, radiotherapy, chemotherapy, revision or primary surgery, and primary tumor metastasis. Correlations between these factors and IF were analyzed by Kaplan–Meier survival and logistics regression analyses. Results The 178 patients included 108 males and 70 females with a mean age of 48.09±16.21 (6–78) years and a mean follow-up period of 51.18 (24–90) months. The data showed that 17 patients (9.55%) were inflicted with IF, involving the thoracic vertebra in 11 cases, thoracolumbar vertebrae (T12–L1) in 2 cases, and lumbar vertebrae in 4 cases. The mean interval between surgery to IF was 35.18±14.17 (14–59) months. Univariate analysis showed that total vertebral body resection, the number of resected vertebral segments, radiotherapy and multiple tumor resection were potential factors for IF, while multivariate analysis showed that only total vertebral body resection, the number of resected vertebral segments and radiotherapy were independent factors. Conclusion Total vertebra resection, the number of resected vertebral segments (≥2) and radiotherapy before and after operation were significant risk factors related to IF.

Background: In Phase III trials, ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) + various endocrine therapy (ET) partners has demonstrated significantly prolonged progression-free survival vs placebo (PBO) + ET in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC). Here we further evaluate the safety of RIB-based regimens of interest for the proposed indication (i.e. with a non-steroidal aromatase inhibitor [NSAI] or fulvestrant [FUL]) using pooled data from three Phase III trials (MONALEESA [ML]-2 [NCT01958021], -3 [NCT02422615], and -7 [NCT02278120]). Methods: Postmenopausal pts with HR+, HER2– ABC received RIB (600 mg/day; 3-weeks-on/1-week-off) or PBO + letrozole (LET; 2.5 mg/day; ML-2 [no prior ET for ABC]) or FUL (500 mg, Days 1 and 15 of Cycle 1, then Day 1 of every cycle thereafter; ML-3; no or ≤1 prior line of ET for ABC]). Premenopausal pts (ML-7; no prior ET and ≤1 chemotherapy for ABC]) received RIB or PBO + anastrozole (1 mg/day)/LET (2.5 mg/day) + goserelin (3.6 mg every 28 days). Adverse events (AEs) were characterized per Common Terminology Criteria for Adverse Events v4.03; safety analyses included time to first event, duration of event, and rate of associated RIB/PBO discontinuations. Results: Data for 1883 pts were pooled; 1065 pts received RIB + ET and 818 pts received PBO + ET (median exposure to study treatment: 17 and 13 months, respectively). Exposure-adjusted incidence rates for AEs of special interest were 561 and 131 per 100 pt-years in the RIB and PBO arms, respectively. The most common all-causality Grade 3/4 AEs (≥10% in any arm; RIB vs PBO) were neutropenia (59% vs 2%), leukopenia (18% vs 1%), and hypertension (13% vs 13%). A new Fridericia's corrected QT interval (QTcF) >480 ms occurred in (n/N) 52/1054 (5%) vs 11/814 (1%) pts in the RIB vs PBO arms; a new QTcF >500 ms occurred in 14/1054 (1%) vs 1/814 (<1%) pts. Median time to first event for Grade ≥2 neutropenia, elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), and QTc prolongation in the RIB arm was 2, 12, and 2 weeks, respectively; median duration of first Grade ≥2 event was 4, 4, and 2 weeks. In the RIB arm vs PBO arms, 7% vs 3% of pts discontinued study treatment due to AEs; common all-grade AEs leading to RIB/PBO discontinuation (≥2% in any arm) were elevated ALT (4% vs <1%) and elevated AST (2% vs 1%). Discontinuation due to QT prolongation occurred in 4 pts in the RIB arm and 2 in the PBO arm (both <1%). All-grade serious AEs occurred in 25% of pts in the RIB arm vs 15% of pts in the PBO arm. Conclusions: RIB in combination with various ET partners continues to demonstrate a predictable and manageable tolerability profile across a broad population of pts with HR+, HER2– ABC. Citation Format: Burris HA, Chan A, Im S-A, Chia S, Tripathy D, Esteva FJ, Campone M, Bardia A, Kong O, Bao W, Diaz-Padilla I, Rodriguez Lorenc K, Yardley DA. Ribociclib + endocrine therapy in hormone receptor-positive, HER2-negative advanced breast cancer: A pooled safety analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-15.

Background: In three separate Phase III randomized, placebo-controlled trials, ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) + various endocrine therapy (ET) partners prolonged progression-free survival (PFS) vs placebo (PBO) + ET in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC). Here we further evaluate the efficacy of RIB-based regimens of interest (i.e. with a non-steroidal aromatase inhibitor [NSAI] or fulvestrant [FUL]) in pts who were ET-naïve in the ABC setting, using pooled data from three Phase III trials: MONALEESA (ML)-2 (NCT01958021; all pts), ML-3 (NCT02422615; no prior ET for ABC subgroup only), and ML-7 (NCT02278120; RIB + NSAI subgroup only). Methods: Postmenopausal pts with no prior ET for ABC received RIB (600 mg/day; 3-weeks-on/1-week-off) or PBO + either letrozole (2.5 mg/day) in ML-2 or FUL (500 mg every 28 days, with an additional dose on Day 15 of Cycle 1) in ML-3. In ML-7, premenopausal pts with no prior ET and ≤1 line of chemotherapy for ABC received RIB or PBO + goserelin (3.6 mg every 28 days) + NSAI (anastrozole [1 mg/day]/letrozole [2.5 mg/day]). The primary endpoint of all three trials was locally assessed PFS. Secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), and duration of response (DoR; ML-3 and -7). DoR was an exploratory endpoint in ML-2. Results: Data were pooled for 820 pts treated with RIB + ET (ML-2: n=334; ML-3: n=238; ML-7: n=248) and 710 pts treated with PBO + ET (ML-2: n=334; ML-3: n=129; ML-7: n=247). As of the data cutoffs (ML-2: January 2, 2017; ML-3: November 3, 2017; ML-7: August 20, 2017), in the RIB + ET vs PBO + ET arms, 385 (47%) vs 234 (33%) pts remained on-treatment; the most common reason for discontinuation was disease progression (n=292 [36%] vs n=391 [55%]). In this pooled analysis, median PFS was prolonged for RIB + ET vs PBO + ET, with a hazard ratio of 0.570 (95% confidence interval [CI] 0.491–0.662); median PFS was 25.3 months (95% CI 23.9–29.6) vs 15.6 months (95% CI 14.4–16.9), respectively. Consistent PFS benefit for RIB + ET vs PBO + ET was observed across pt subgroups, including ECOG performance status, age, race, or presence/absence of liver and/or lung metastases or bone-only disease. Among all pts in the pooled analysis, the ORR was 41% for RIB + ET vs 28% for PBO + ET and the CBR was 79% vs 70%, respectively. In pts with measurable disease at baseline (RIB + ET: n=639; PBO + ET: n=542), the ORR was 51% for RIB + ET vs 37% for PBO + ET and the CBR was 79% vs 68%, respectively. In the RIB + ET vs PBO + ET arms, the median DoR was 26.7 months vs 20.0 months. A decrease in best percentage change from baseline in the sum of longest diameters per RECIST was observed in 86% of pts receiving RIB + ET vs 73% of pts receiving PBO + ET. Conclusions: RIB in combination with various ET partners demonstrates improved clinical outcomes vs PBO + ET across a broad population of pts with HR+, HER2– ABC. These data provide further support for the use of RIB-based combinations in pre- and postmenopausal pts with HR+, HER2– ABC who have received no prior ET for advanced disease. Citation Format: Tripathy D, Hortobagyi G, Chan A, Im S-A, Chia S, Yardley D, Esteva FJ, Hurvitz S, Kong O, Bao W, Rodriguez Lorenc K, Diaz-Padilla I, Slamon DJ. First-line ribociclib + endocrine therapy in hormone receptor-positive, HER2-negative advanced breast cancer: A pooled efficacy analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-05.