Purpose We evaluated the noninferiority of dexamethasone (DEX) on day 1, with sparing on days 2 and 3, combined with neurokinin-1 receptor antagonist (NK-RA) and palonosetron (Palo) compared with the 3-day use of DEX in highly-emetogenic chemotherapy (HEC). Patients and Methods Patients who were scheduled to receive HEC (cisplatin ≥ 50 mg/m or anthracycline plus cyclophosphamide) were randomly assigned to receive either DEX on days 1 to 3 (Arm D3) or DEX on day 1 and placebo on days 2 and 3 (Arm D1) combined with NK-RA and Palo. The primary end point was complete response (CR), defined as no emesis and no rescue medications during the overall (0 to 120 h) phase. The noninferiority margin was set at -15.0% (Arm D1 - Arm D3). Results A total of 396 patients-196 and 200 patients in Arms D3 and D1, respectively-were evaluated. CR rates during the overall period were 46.9% for Arm D3 and 44.0% for Arm D1 (95% CI, -12.6% to 6.8%; P = .007). CR rates during the acute (0 to 24 h) phase were 63.3% and 64.5% for Arms D3 and D1, respectively (95% CI, -8.1% to 10.6%; P < .001), and they were 56.6% and 51.5%, respectively, during the delayed (24 to 120 h) phase (95% CI, -14.8% to 4.6%; P = .023). Hot flushes and tremors were observed more frequently as DEX-related adverse events on days 4 and 5 in Arm D3, whereas anorexia, depression, and fatigue were observed more frequently on days 2 and 3 in Arm D1. As an indication of quality of life, global health status was similar in both arms. Conclusion Antiemetic DEX administration on days 2 and 3 can be spared when combined with NK-RA and Palo in HEC.

Purpose Chemotherapy-induced nausea and vomiting (CINV) decrease patient quality of life (QOL). We evaluated the efficacy of adding 5 mg Olz to a three-drug steroid-sparing antiemetic regimen (aprepitant, palonosetron, and dexamethasone-sparing after day two) for breast cancer (BC) patients receiving anthracycline plus cyclophosphamide (AC) chemotherapy. Patients and Methods We retrospectively reviewed the records of 177 BC patients with no previous highly emetogenic chemotherapy history receiving AC plus the steroid-sparing three-drug regimen or the steroid-sparing four-drug regimen including Olz 5mg at our hospital between January 2012 and December 2018. The primary endpoint was complete response (CR), defined as no vomiting and no usage of rescue medication during the first AC cycle. We analyzed the odds ratio (OR) of the CR with 95% confidence interval (CI) in the three-drug group against the four-drug group. The OR was adjusted for types of anticancer drugs by the Cochran–Mantel–Haenszel (CMH) test. Secondary endpoints were incidences of nausea, anorexia, fatigue, and somnolence during the first cycle. Results Compared to the three-drug group, the four-drug group demonstrated high incidence of no vomiting (71% vs 95%), a similar incidence of no rescue medication usage (50% vs 51%), and a similar CR rate (45% vs 49%). The OR of the CR rate in the three-drug group against the four-drug group after CMH adjustment for drug type was 0.958 (95% CI, 0.46–1.98). Compared to the three-drug group, the four-drug group demonstrated identical incidence of nausea (66%), but lower incidences of anorexia (78% vs 35%) and fatigue (86% vs 73%). The incidence of somnolence in the four-drug group was 49%. We did not have data of somnolence for the three-drug group in the records. Conclusion Adding 5 mg Olz to the steroid-sparing three-drug combination can reduce vomiting, anorexia, and fatigue, although there was no difference in CR rate.

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.

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IntroductionDexamethasone (DEX) is administered for multiple days to prevent chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy (HEC); however, its notorious side effects have been widely reported. Although our multicentre randomised double-blind comparative study verified non-inferiority of sparing DEX after day 2 of chemotherapy when combined with neurokinin-1 receptor antagonist (NK1-RA) and palonosetron (Palo) for patients receiving HEC regimen, DEX sparing was not non-inferior in patients receiving cisplatin (CDDP)-based HEC regimens in subgroup analysis. Recently, the efficacy of the addition of olanzapine (OLZ) to standard triple antiemetic therapy on HEC has been demonstrated by several phase III trials. This study aims to confirm non-inferiority of DEX sparing when it is combined with NK-1RA, Palo and OLZ in patients receiving CDDP-based HEC regimens.Methods and analysisThis is a randomised, double-blind, phase III trial. Patients who are scheduled to receive CDDP ≥50 mg/m2as initial chemotherapy are eligible. Patients are randomly assigned to receive either DEX on days 1–4 or DEX on day 1 combined with NK1-RA, Palo and OLZ (5 mg). The primary endpoint is complete response (CR) rate, defined as no emesis and no rescue medications during the delayed phase (24–120 hours post-CDDP administration). The non-inferiority margin is set at −15.0%. We assume that CR rates would be 75% in both arms. Two hundred and sixty-two patients are required for at least 80% power to confirm non-inferiority at a one-sided significance level of 2.5%. After considering the possibility of attrition, we set our final required sample size of 280.Ethics and disseminationThe institutional review board approved the study protocol at each of the participating centres. The trial result will be presented at international conferences and published in peer-reviewed journals.Trial registration numberUMIN000032269.