P1.01-71 Bone Metastases and Skeletal-Related Events in Patients with Metastatic NSCLC Treated with ICIs: A Multi-Institutional Study

Skeletal-related events (SRE) occur frequently in patients (pts) with metastatic NSCLC (mNSCLC) and confer a poor prognosis. Data on SRE and the effects of bone modifying agents (BMA) in NSCLC pts treated with immune checkpoint inhibitors (ICI) are limited as is the effect of bone modifying agents (BMA) on development of SRE and overall survival (OS). Here we report the incidence, impact on survival, and risk factors for SRE in pts with mNSCLC treated with ICI in a multi-institutional cohort. We conducted a retrospective study of pts with mNSCLC treated with ICI at our institutions from 2014 to 2017. Overall survival (OS) was calculated from the date of ICI initiation to death from any cause or last follow-up. Cox regression model was used to study the association between OS and baseline bone metastases (BM). The associations between SRE and categorical outcomes were studied using chi-square/Fisher’s exact test. The study was approved by each institution’s ethics review board. Table 1Multivariate survival analysis.ParameterLevelHazard Ratio95% HR Confidence LimitsP-valueBM at baselineAbsentRef<0.0001Present1.8471.414-2.413ECOG0Ref0.000611.4941.017-2.19621.5060.969-2.34133.7881.442-9.949HistologyAdenocarcinomaRef0.969Squamous1.0570.786-1.420Lines of Therapy1Ref0.000721.5801.123-2.223≥32.0641.417-3.005 Open table in a new tab We identified a cohort of 330 pts: 259 (72%) treated in second line or beyond; 211 (64%) received nivolumab; median age 63.4; median OS 10.4 mo (95% CI: 8.6, 12.5). In our cohort, 124 (38%) pts had BM at time of ICI, and 43 (13%) developed SRE after ICI (median 2.8 months; 19 pathologic fractures, 1 cord compression, 26 palliative radiation, 8 surgery). Patients with BM at ICI had shorter OS after controlling for ECOG, histology, and line of therapy (Table 1; Hazard Ratio 1.847; 95% CI 1.414 - 2.413; p <0.0001) compared to pts without baseline BM. Development of SRE was associated with presence of BM at baseline but not age, histology, or mutation status (EGFR, KRAS, and TP53). The use of BMA was not associated with OS or decreased risk of SRE. The development of new or progression of existing BM (22% of pts) during ICI was associated with a worse prognosis (mOS 7.1 vs 11.6 mo, p=0.017). Bone metastases and SRE are a significant cause of morbidity in pts with mNSCLC treated with ICI. The presence of BM at baseline was associated with a worse prognosis after controlling for multiple clinical characteristics. In our cohort, the use of BMA was not associated with decreased risk of developing SRE, osseous progression, or survival.