The efficacy and safety of denosumab in gastrointestinal cancer patients receiving short-term periodic steroid premedication for prevention of chemotherapy-induced nausea and vomiting (ESPRESSO-02/HGCSG1602).

Abstract Purpose We previously reported that the periodic premedication of glucocorticoids during chemotherapy for gastrointestinal cancer (GIC) caused the reduction of bone mineral densities (BMD) (ESPRESSO-01). We conducted this study to evaluate the efficacy and safety of denosumab in the prevention of chemotherapy-induced decreased BMD. Methods Forty-two Japanese patients were studied. Denosumab was administered as a single 60 mg subcutaneous injection before the start of chemotherapy. The primary endpoint was BMD change in the lumbar spine from baseline to 16 weeks. Secondary endpoints were changes in serum cross-linked N-telopeptides of type I collagen (sNTX) and bone alkaline phosphatase (sBAP), complications including hypocalcemia and osteonecrosis of the jaw, new bone fractures, changes in the Japanese Osteoporosis Quality of Life Questionnaire. Results Lumbar spine BMD significantly increased in 71.4% of cases: 2.772% (95% CI, 1.350–4.195%: P < 0.0001). There were also significant decreases in sNTX (P = 0.034) and sBAP levels (P < 0.001). Although one case (2.4%) of jaw osteonecrosis was diagnosed, no fractures occurred. In a cross-trial comparison with ESPRESSO-01, there was no significant difference in the incidence of National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher adverse events. However, inclusion of grade ≤2 showed significantly higher incidence of hypocalcemia with any CTCAE grade in ESPRESSO-02 (28.4% in ESPRESSO-01, 54.8% in ESPRESSO-02, P = 0.006) Conclusion Denosumab administration prevented secondary BMD reduction in GIC patients undergoing chemotherapy, and was associated with decreased serum levels of the bone turnover markers BAP and NTX.