LBA63 Placebo-controlled, double-blinded phase Ⅲ study comparing dexamethasone on day 1 with dexamethasone on days 1 to 4, with combined neurokinin-1 receptor antagonist, palonosetron, and olanzapine in patients receiving cisplatin-containing highly emetogenic chemotherapy: SPARED trial

Abstract

Background: Despite a range of treatment options, about 25% of patients with painful bone metastases suffer from uncontrolled pain. This Phase 3, randomized, double-blind, placebo-controlled trial (24-week treatment/24-week follow-up) examined the efficacy and safety of tanezumab, a monoclonal antibody against nerve growth factor, in subjects with moderate to severe cancer pain due to bone metastasis or multiple myeloma receiving background opioid therapy.Methods: Subjects from 15 countries (Europe, South America, Asia-Pacific regions) were randomized and received double-blind subcutaneous placebo or tanezumab 20 mg at baseline, week 8, and week 16 while continuing optimized opioid therapy. The primary endpoint was change in daily average pain intensity (0 ¼ no pain to 10 ¼ worst possible pain) at the index bone metastasis cancer pain site from baseline to week 8, evaluated via analysis of covariance. Adverse events (AEs) and pre-specified joint safety events (rapidly progressive osteoarthritis [RPOA] type 1 or 2, primary osteonecrosis, subchondral insufficiency fracture, or pathologic fracture; adjudicated by an external expert committee) were also assessed.Results: Tanezumab 20 mg (N ¼72) met the primary endpoint by demonstrating significantly (p ¼ 0.038 with a ¼ 0.048) greater improvement in daily average pain intensity at the index bone metastasis cancer pain site at week 8 compared with placebo (N ¼ 73). LS mean (95% CI) change in pain was -1.25 (-1.94, -0.55) for placebo and -2.03 (-2.73, -1.33) for tanezumab 20 mg. Differences past week 8 were not statistically significant. During the treatment period, the AE profile of tanezumab 20 mg was generally consistent with AEs expected in subjects with cancer pain due to bone metastasis and the known safety profile of tanezumab. The proportion of subjects adjudicated with a pre-specified joint safety event during the study was 0% for placebo and 2.8% for tanezumab 20 mg (pathological fracture near the site of bone metastasis, n ¼ 2). No events of RPOA were reported.Conclusions: Tanezumab 20 mg improved metastatic cancer-related bone pain compared with placebo and the AE profile was generally consistent with previous studies of tanezumab.Clinical trial identification: NCT02609828.

Combination Antiemetic Therapy for Chemotherapy-Induced Nausea and Vomiting in Patients with NSCLC Receiving Carboplatin-Based Chemotherapy

“… 28 These results suggest that the addition of olanzapine to standard triplet antiemetic therapy is a promising option to improve the control of delayed nausea in patients at high risk of CINV who receive CBDCA + PEM. Concerning DEX, a phase III study reported at ESMO2021 29 aimed to clarify the non-inferiority of DEX on day 1 to DEX on days 1–4 when combined with an NK1RA, palonosetron, and olanzapine in patients receiving cisplatin-based highly emetogenic chemotherapy. In that trial, the primary endpoint of the complete response rate in the delayed phase was statistically met, and DEX on day 1 was non-inferior to DEX on days 1–4.…”