2167P Are bone targeted agents (BTAs) still useful in times of immunotherapy? The SAKK 80/19 BTA study

Patients (pts) with bone metastases (BM) from solid tumors often have additional treatment with BTAs to avoid symptomatic skeletal events (SSEs) such as clinically significant pathological fracture, radiation therapy to the bone, surgery to the bone, or spinal cord compression. The absolute value of BTA treatment in the era of immunotherapy (IO) is unknown. Pts with BM treated with IO within the Alpine Tumor Immunology Registry who received an additional BTA (denosumab, zoledronic acid) were compared with pts who have not received a BTA. The primary endpoint was time to first SSE. Continuous data was summarized as median and range, categorical data using frequency counts and percentages. Kaplan-Meier estimates were used to describe and visualize the effect of categorical variables. In total, 197 pts with BM and treated with IO such as nivolumab (48%), pembrolizumab (40%), atezolizumab (12%), ipilimumab (9%) and other IO (5%) were included. The most frequent tumor types were lung cancer (50%), malignant melanoma (11%), renal cell cancer (10%) and bladder cancer (9%), respectively. One hundred and twenty-two pts (62%) received a BTA treatment (91% denosumab). The median treatment duration of a BTA was 178 days (min: 1 day, max: 2010 days). Out of the 197 pts, 47 pts (24%) experienced at least one SSE, 100 pts (51%) had bone pain, and 11 pts (6%) developed osteonecrosis of the jaw (ONJ). The percentage of pts without a SSE at fixed time points was numerically higher if treated with a BTA (e.g., at 6 month, 86% [95% CI: 79%-91%] versus 78% [95% CI: 66%-86%]), but no significant difference in time to first SSE (HR 0.79; 95% CI 0.44-1.42, log-rank p=0.43) or time to first bone pain (HR 1.1; 95% CI 0.73-1.69, log-rank p=0.6) between these two groups could be detected. The median OS for pts treated with a BTA was 1.7 years (95% CI: 1.1-2.0) and 1.7 years (95% CI: 1.4 -2.9) for pts not received a BTA. No significant difference in time to first SSE or bone pain was observed between pts who have received a BTA or not when treated with IO. In contrast, 6% of these pts experienced an ONJ. Based on these retrospective results the indication of BTAs in cancer pts under treatment with IO must be challenged. Further prospective evaluation in a larger patient cohort is on the way.