Asian Subgroup Analysis Research Articles

208O Asian subgroup analysis of the THOR phase III study: Erdafitinib versus chemotherapy in patients with advanced or metastatic urothelial cancer and selected fibroblast growth factor receptor alterations

208O Asian subgroup analysis of the THOR phase III study: Erdafitinib versus chemotherapy in patients with advanced or metastatic urothelial cancer and selected fibroblast growth factor receptor alterations

97P Asian subgroup analysis of the phase III LEAP-017 trial of lenvatinib plus pembrolizumab vs standard-of-care in previously treated metastatic colorectal cancer (mCRC)

97P Asian subgroup analysis of the phase III LEAP-017 trial of lenvatinib plus pembrolizumab vs standard-of-care in previously treated metastatic colorectal cancer (mCRC)

EP11.02-06 Atezolizumab vs Single-Agent Chemo in NSCLC Patients Ineligible for a 1L Platinum Regimen: Asian Subgroup Analysis of IPSOS

EP11.02-06 Atezolizumab vs Single-Agent Chemo in NSCLC Patients Ineligible for a 1L Platinum Regimen: Asian Subgroup Analysis of IPSOS

Avelumab first-line maintenance plus best supportive care (BSC) vs. BSC alone for advanced urothelial carcinoma: JAVELIN Bladder 100 Asian subgroup analysis.

The phase 3 JAVELIN Bladder 100 trial showed significantly prolonged overall survival (OS) with avelumab first-line maintenance + best supportive care (BSC) vs. BSC alone in patients with advanced urothelial carcinoma (UC) that had not progressed with first-line platinum-containing chemotherapy. Here, efficacy and safety were assessed from the initial analysis of the JAVELIN Bladder 100 trial (data cutoff October 21, 2019) in patients enrolled in Asian countries. Patients with locally advanced or metastatic UC that had not progressed with 4 to 6 cycles of first-line platinum-containing chemotherapy (gemcitabine + cisplatin or carboplatin) were randomized 1:1 to receive avelumab first-line maintenance + BSC or BSC alone, stratified by best response to first-line chemotherapy and visceral vs. nonvisceral disease when initiating first-line chemotherapy. The primary endpoint was OS assessed from randomization in all patients and patients with PD-L1+ tumors (Ventana SP263 assay). Secondary endpoints included progression-free survival (PFS) and safety. A total of 147 patients in JAVELIN Bladder 100 were enrolled in Asian countries (Hong Kong, India, Japan, South Korea, and Taiwan). In this Asian subgroup, 73 and 74 patients received avelumab + BSC or BSC alone, respectively. Median OS was 25.3 months (95% CI, 18.6 to not estimable [NE]) in the avelumab + BSC arm vs. 18.7 months (95% CI, 12.8-NE) in the BSC alone arm (hazard ratio [HR], 0.74 [95% CI, 0.43-1.26]); median PFS was 5.6 months (95% CI, 2.0-7.5) vs. 1.9 months (95% CI, 1.9-1.9), respectively (HR, 0.58 [95% CI, 0.38-0.86]). In the avelumab + BSC vs. BSC alone arms, grade ≥3 treatment-emergent adverse events (any causality) occurred in 44.4% vs. 16.2%, respectively. The most common grade ≥3 treatment-emergent adverse events in the avelumab + BSC arm were anemia (9.7%), amylase increased (5.6%), and urinary tract infection (4.2%). Efficacy and safety results for avelumab first-line maintenance in the Asian subgroup of JAVELIN Bladder 100 were generally consistent with those in the overall trial population. These data support the use of avelumab first-line maintenance as standard of care for Asian patients with advanced UC that has not progressed with first-line platinum-containing chemotherapy. NCT02603432.

158MO Niraparib with abiraterone acetate and prednisone (NIRA+AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR+) gene alterations: Asian subgroup analysis of the MAGNITUDE study

158MO Niraparib with abiraterone acetate and prednisone (NIRA+AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR+) gene alterations: Asian subgroup analysis of the MAGNITUDE study

1031P Tislelizumab (TIS) versus docetaxel (TAX) as second- or third-line therapy in previously treated patients (pts) with locally advanced non-small cell lung cancer (NSCLC): Asian versus non-Asian subgroup analysis of the RATIONALE-303 study

In RATIONALE-303 (NCT03358875), TIS significantly improved overall survival (OS) vs TAX in the intent-to-treat population (ITT) at the interim analysis (IA). TIS was later approved in China for advanced or metastatic NSCLC after progression on prior platinum-based chemotherapy. At the final analysis (FA), the co-primary endpoint of OS in the programmed death-ligand 1 (PD-L1, VENTANA SP263 assay) tumor cell ≥ 25% population was met, and TIS continued to improve OS compared with TAX in the ITT. Here we report FA results from the Asian vs non-Asian subgroups.

Asian Subgroup Analysis of the REMISSIO Study: A Long-Term Efficacy and Safety Study of Paliperidone Palmitate 3-month Formulation in Patients with Stable Schizophrenia in a Naturalistic Clinical Setting.

ObjectiveTo evaluate the long-term efficacy and safety of three-monthly paliperidone palmitate (PP3M) in Asian patients with stable schizophrenia in a naturalistic setting.MethodsAsian patients recruited between May 2016 and March 2018 from the prospective, single-arm, non-randomized, open-label, multi-national REMISSIO study were analyzed. Patients received PP3M over 12 months following ≥ 4 months of treatment with one-monthly paliperidone palmitate. The primary efficacy endpoint was the proportion of patients who achieved symptomatic remission. Other endpoints were changes in Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) total scores, hospitalization rates, and safety.ResultsA total of 71 patients (23.3%) were Asian (South Korea 33, Malaysia 21, Taiwan 17); 95.8% of patients completed the study. At LOCF, 71% of Asian patients achieved symptomatic remission compared to the overall population (n = 172/303, 56.8%). Improvements in mean (standard deviation) PANSS and PSP total scores from baseline to LOCF in Asian patients and overall population were clinically significant. A lower proportion of Asian patients had ≥ 1 psychiatric hospitalization after PP3M treatment (n = 1/70, 1.4%) than during the 12 months before (n = 12/70, 17.1%); compared with patients in the overall population after (n = 8/303, 2.6%) and before PP3M treatment (n = 37/303, 12.2%). The overall incidence of treatment-emergent adverse events across Asian patients was 62.9% compared to 53.1% in the overall population. Safety findings were consistent with the known safety profile of PP3M.ConclusionOur findings confirm existing evidence on the efficacy and tolerability of PP3M in Asian patients with stable schizophrenia over 12 months of treatment.

MO36-4 Asian subgroup analysis in global POLAR program of calmangafodipir on top of mFOLFOX6 for the prevention of CIPN

Calmangafodipir (CaM) is a superoxide dismutase mimetic and iron chelator and expected, based on its mechanism, to prevent chemotherapy induced peripheral neuropathy (CIPN). The global POLAR program was conducted to evaluate the efficacy in prevention of CIPN in colorectal cancer (CRC) patients treated with oxaliplatin. In the readout of the POLAR program, the primary endpoint was not met (ESMO-GI 2021). Here we report the results of subgroup analysis of the Asian population in the POLAR program.

Efficacy and Safety of Ceritinib 450 mg/day with Food and 750 mg/day in Fasted State in Treatment-Naïve Patients with ALK+ Non-Small Cell Lung Cancer: Results from the ASCEND-8 Asian Subgroup Analysis.

Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non-small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial. Key efficacy endpoints were blinded independent review committee (BIRC)-assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events. At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively. Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.

Long-term Safety and Efficacy of Esketamine Nasal Spray Plus an Oral Antidepressant in Patients with Treatment-resistant Depression- an Asian Sub-group Analysis from the SUSTAIN-2 Study.

ObjectiveTo evaluate the long-term safety and efficacy of intranasal esketamine in patients with treatment-resistant depression from the Asian subgroup of the SUSTAIN-2 study.MethodsSUSTAIN-2 was a phase 3, open-label, single-arm, multicenter study comprising a 4-week screening, 4-week induction, 48-week optimization/maintenance, and 4-week follow-up (upon esketamine discontinuation) phase. Patients with treatment-resistant depression received esketamine plus an oral antidepressant during the treatment period.ResultsThe incidence of ≥ 1 serious treatment-emergent adverse event (TEAE) among the 78 subjects from the Asian subgroup (Taiwan 33, Korea 26, Malaysia 19) was 11.5% (n = 9); with no fatal TEAE. 13 Asian patients (16.7%) discontinued esketamine due to TEAEs. The most common TEAEs were dizziness (37.2%), nausea (29.5%), dissociation (28.2%), and headache (21.8%). Most TEAEs were mild to moderate in severity, transient and resolved on the same day. Upon discontinuation of esketamine, no trend in withdrawal symptoms was observed to associate long-term use of esketamine with withdrawal syndrome. There were no reports of drug seeking, abuse, or overdose. Improvements in symptoms, functioning and quality of life, occurred during in the induction phase and were generally maintained through the optimization/maintenance phases of the study.ConclusionThe safety and efficacy of esketamine in the Asian subgroup was generally consistent with the total SUSTAIN-2 population. There was no new safety signal and no indication of a high potential for abuse with the long-term (up to one year) use of esketamine in the Asian subgroup. Most of the benefits of esketamine occurred early during the induction phase.

1197P First-line lorlatinib versus crizotinib in ALK-positive non-small cell lung cancer: Asian subgroup analysis of CROWN

Lorlatinib, a 3rd-generation ALK inhibitor, significantly prolonged progression-free survival (PFS) vs crizotinib in the CROWN trial in patients with untreated ALK-positive non-small cell lung cancer (NSCLC). We report data from the Asian subgroup of CROWN.

608P Apalutamide (APA) efficacy and safety in Asian patients with metastatic castration-sensitive prostate cancer (mCSPC)

In TITAN study, the addition of APA to androgen deprivation therapy (ADT) significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) for mCSPC patients (Chi, NEJM, 2019; Chi et al, J Clin Oncol 39(6_suppl): 11, 2021). As there can be regional differences in outcomes, this TITAN Asian subgroup analysis was conducted.

P84.09 Asian Subgroup Analysis of a Phase II Study Evaluating Lorlatinib Efficacy in Previously Treated ALK-Positive Advanced NSCLC

Lorlatinib is a selective, potent, brain-penetrant, third-generation tyrosine kinase inhibitor (TKI) that targets ALK and ROS1. In a global Phase II trial, lorlatinib showed substantial overall and intracranial activity in patients with ALK- or ROS1-positive advanced non-small cell lung cancer (NSCLC). Here we report the efficacy and biomarkers of lorlatinib from the Asian subgroup analysis of this trial.

P85.04 Capmatinib in Patients with METex14-Mutated Non-Small Cell Lung Cancer: GEOMETRY Mono-1 Asian Subgroup Analysis

P85.04 Capmatinib in Patients with METex14-Mutated Non-Small Cell Lung Cancer: GEOMETRY Mono-1 Asian Subgroup Analysis

Pembrolizumab (pembro) versus standard of care chemotherapy (chemo) in patients with advanced gastric or gastroesophageal junction adenocarcinoma: Asian subgroup analysis of KEYNOTE-062.

4523 Background: First-line treatment with pembro or pembro + chemo vs chemo alone was evaluated in patients with PD-L1 combined positive score (CPS) ≥1, HER2-negative advanced gastric cancer in the randomized, active-controlled, phase 3 KEYNOTE-062 study (NCT02494583). We present results from the Asian subpopulation receiving pembro monotherapy or chemo. Methods: Eligible patients were randomly assigned 1:1:1 to pembro 200 mg, pembro + chemo (cisplatin + 5-FU or capecitabine), or placebo + chemo every 3 weeks for ≤35 cycles (~2 years). Randomization was stratified by region, disease status, and fluoropyrimidine treatment. Primary end points for this analysis were overall survival (OS) in patients with CPS ≥1 and patients with CPS ≥10; progression-free survival (PFS) and objective response rate (ORR) were exploratory end points. Data cutoff was March 26, 2019. Results: Globally, 256 patients received pembro monotherapy and 250 received chemo. Pembro was noninferior to chemo for OS in CPS ≥1 per prespecified margins (median OS, 10.6 vs 11.1 months, respectively; HR [99.2% CI], 0.91 [0.69-1.18]). In the Asian population 62 patients received pembro and 61 received chemo; 26 and 22 had CPS ≥10 (Table). Compared with the global population, Asian patients had a higher proportion of ECOG performance status 0, more diagnoses of stomach cancer, and a greater proportion with 0-2 metastatic sites. Median OS was longer with pembro than chemo using both CPS cutoffs (HR [95% CI]: CPS ≥1, 0.54 [0.35-0.82]; CPS ≥10, 0.43 [0.21-0.89]); 12- and 24-month OS rates were higher for pembro using both CPS cutoffs (12-month OS: CPS ≥1, 69% vs 54%; CPS ≥10, 81% vs 68%; 24-month OS: CPS ≥1, 45% vs 23%; CPS ≥10, 54% vs 27%). The HR (95% CI) for PFS was 1.11 (0.76-1.64) for CPS ≥1 and 0.71 (0.36-1.39) for CPS ≥10. Conclusions: In Asian patients with advanced gastric cancer, OS favored pembro in patients with CPS ≥1 and CPS ≥10. Clinical trial information: NCT02494583 . [Table: see text]

1473P - First-line ceritinib versus chemotherapy in patients (pts) with advanced ALK rearranged (ALK+) non-small cell lung cancer (NSCLC): ASCEND-4 Asian subgroup analysis

BackgroundIn global phase III ASCEND-4 study (NCT01283516), ceritinib 750mg/day (fasted), demonstrated statistically significant and clinically meaningful improvement in PFS by BIRC (median, 16.6 mos [95% CI: 12.6, 27.2] vs 8.1 mos [95% CI: 5.8, 11.1]; HR=0.55; p<0.001) compared to chemotherapy (pemetrexed 500mg/m2 + cisplatin 75mg/m2 or carboplatin AUC 5-6, followed by pemetrexed maintenance) in untreated pts with advanced ALK+ NSCLC. Here, we report the efficacy and safety of ceritinib in Asian pts from ASCEND-4 study. MethodsPts with stage IIIB/IV, ALK+(centrally tested IHC), nonsquamous NSCLC, ≥1 measurable lesion per RECIST v1.1, and WHO PS 0–2 were eligible. Efficacy and safety were evaluated in Asian pts who had not received prior systemic anticancer therapy except neo-/adjuvant therapy. Data cutoff: June 24, 2016. ResultsAmong 376 pts randomized (1:1) in the study, 158 pts were Asian, with 76 in ceritinib arm and 82 in chemotherapy arm. Of these, 25 pts (32.9%) in ceritinib arm and 21 (25.6%) in chemotherapy arm had brain metastases at baseline. Median duration of treatment exposure: 64.5 wks (ceritinib, N=76) and 35.0 wks (chemotherapy, N=75). Median duration from randomization to data cutoff: 18.3 mos. Ceritinib demonstrated superior PFS by BIRC (median, 26.3 mos; 95% CI: 8.6, NE; HR=0.66) compared to chemotherapy (Table). Most common (≥50%; all grades; all-causality) AEs in ceritinib arm: diarrhea (85.5%), ALT increased (73.7%), vomiting (73.7%), AST increased (69.7%), and nausea (69.7%). Incidence of grade 3/4 AEs was <6%, except ALT increased (38.2%), GGT increased (22.4%), AST increased (21.1%), fatigue (7.9%), amylase increased (6.6%), and hyperglycemia (6.6%). Only 7 pts (9.2%) discontinued ceritinib due to AEs.Table1473PTableBy BIRC (N*=158)Ceritinib 750mg N=76Chemotherapy N=82Overall response rate (ORR), % [95% CI]65.8 [54.0, 76.3]29.3 [19.7, 40.4]Best overall response, n (%) Complete response (CR) Partial response (PR) Stable disease (SD) Progressive disease (PD) Non-CR/Non-PD Unknown0 50 (65.8) 11 (14.5) 11 (14.5) 2 (2.6) 2 (2.6)0 24 (29.3) 38 (46.3) 6 (7.3) 3 (3.7) 11 (13.4)Disease control rate (DCR), % [95% CI]82.9 [72.5, 90.6]79.3 [68.9, 87.4]M‡=50M‡=24Median DOR, months [95% CI]NE [24.7, NE]16.4 [7.8, NE]n/N (%)14/50 (28.0)8/24 (33.3)% Event-free probability estimates [95% CI]9 months81.2 [67.0, 89.8]76.1 [48.0, 90.4]12 months79.0 [64.5, 88.1]50.8 [22.5, 73.5]15 months70.4 [54.0, 81.9]50.8 [22.5, 73.5]Median PFS, months [95% CI]26.3 [8.6, NE]10.6 [6.7, 15.0]n/N (%)32/76 (42.1)45/82 (54.9)% Event-free probability estimates [95% CI]9 months61.0 [48.4, 71.5]54.7 [41.8, 65.8]12 months61.0 [48.4, 71.5]49.8 [37.1, 61.2]15 months55.9 [43.2, 66.9]39.0 [26.9, 51.0]*Total number of patients included in the full analysis set.‡Total number of patients with confirmed complete response or partial response. n: Total number of events included in the analysis. N: Total number of patients included in the analysis. ConclusionsIn Asian pts with ALK+ NSCLC, ceritinib demonstrated durable and clinically meaningful efficacy and a safety profile consistent with overall ASCEND-4 study results. Clinical trial identificationNCT01828099. Editorial acknowledgementShilpa Garg, Novartis Healthcare Pvt Ltd. Legal entity responsible for the studyNovartis Pharmaceuticals Corporation. FundingNovartis Pharmaceuticals Corporation. DisclosureD.S. Tan: Honoraria (self): Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda; Advisory / Consultancy: Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli-lily, Loxo; Research grant / Funding (self): Novartis, AstraZeneca, GlaxoSmithKline, Bayer, Pfizer; Travel / Accommodation / Expenses: Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche,Takeda. S. Geater: Advisory / Consultancy: Boehringer Ingelheim; Honoraria (institution): AstraZeneca, Boehringer Ingelheim; Research grant / Funding (institution): AstraZeneca, Roche, Novartis, Boehringer Ingelheim; Full / Part-time employment: Prince of Songkla Univerisity. C.J. Yu: Honoraria (self): Roche, AstraZeneca, Ono pharma, Boehringer Ingelheim; Advisory / Consultancy: Roche, AstraZeneca, Ono pharma, Boehringer Ingelheim. T.C. Hsia: Advisory / Consultancy: Norvatis, Lilly, AZ, Roche local speaker. M.C. Lin: Advisory / Consultancy: AZ, Novartis, BI, Roche. V. Sriuranpong: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca, Novartis, Roche, Pfizer, Eisai, Boehringer, Taiho, MSD, BMS, Amgen; Research grant / Funding (institution): AstraZeneca, Novartis, Roche, Pfizer, Boehringer, Eisai, Taiho, Lilly, MSD. P. Sen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. F. Branle: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. M. Shi: Shareholder / Stockholder / Stock options: Novartis stock; Full / Part-time employment: Novartis. Y.L. Wu: Honoraria (self): AZ, Roche, Eli Lilly, Pfizer, MSD, BMS, BI; Advisory / Consultancy: AZ, Roche, BI; Research grant / Funding (institution): AZ, Roche. All other authors have declared no conflicts of interest.

Association of dopamine D2 receptor gene polymorphisms with prolactin levels related to risperidone treatment: A systematic review and meta-analysis.

Dopamine D2 receptor (DRD2) polymorphisms are inconsistently associated with elevated prolactin levels related to risperidone treatment. The aim of this systematic review and meta-analysis was to investigate whether DRD2 polymorphisms could modulate prolactin levels in patients treated with risperidone. Three electronic databases (PubMed, EMBASE and the Cochrane Library) were searched for studies investigating the effect of DRD2 polymorphisms on prolactin levels in patients treated with risperidone until May 2018. Summary standard mean differences (SMDs) and 95% confidence intervals (CIs) were calculated with Hedges' g tests for effect estimates using random effects models. The heterogeneity, sensitivity, univariable meta-regression, subgroup analyses and publication biases were calculated. After initially identifying 886 studies, 772 patients from eight studies were included. Summary SMDs indicated that compared with A1 non-carriers, Taq1A A1 carriers did not have different risperidone-related prolactin levels (SMD: 0.13; 95% CI: -0.18 to 0.43; P=0.423) among patients with schizophrenia (SCZ; SMD: 0.07; 95% CI: -0.14 to 0.29; P=0.505) or among those without SCZ (SMD: 0.16; 95% CI: -0.39 to 0.71; P=0.562). There was no significant difference between Del carriers and Del non-carriers with regard to risperidone-related prolactin levels (SMD: -0.00; 95% CI: -0.59 to 0.58; P=0.996). In an Asian subgroup analysis, we also noted that compared with Taq1A A1A2 carriers, Taq1A A1A1 carriers had lower prolactin levels (SMD: -0.34; 95% CI: -0.66 to -0.02; P=0.040). However, there was no significant difference in prolactin levels between A1A1 carriers and A2A2 carriers (SMD: -0.27; 95% CI: -0.60 to 0.05; P=0.098), or between A2 carriers and A2 non-carriers (SMD: 0.29; 95% CI: -0.01 to 0.59; P=0.059). Based on univariable meta-regression analyses, the effects of publication year, study design, ethnicity, comparison groups and study quality could bias the identified association of DRD2 Taq1A with risperidone-related prolactin levels. The findings of this study suggest that there is no significant difference between Taq1A A1 carriers and non-A1 carriers with regard to risperidone-related prolactin levels. As there were few A1 homozygotes, large prospective studies with robust designs are still needed to investigate whether A1A1 could affect risperidone-related prolactin levels in the Asian population.

Everolimus for the treatment of advanced gastrointestinal or lung nonfunctional neuroendocrine tumors in East Asian patients: a subgroup analysis of the RADIANT-4 study.

BackgroundIn RADIANT-4, everolimus showed an improvement of 7.1 months in median progression-free survival (PFS) vs placebo among patients with advanced, well-differentiated, nonfunctional neuroendocrine tumors (NETs) of gastrointestinal (GI) or lung origin. The present analysis focuses on the effect of everolimus on the East Asian-subgroup population of the RADIANT-4 study.MethodsPatients were randomized to receive everolimus 10 mg/day or matching placebo. The primary end point was PFS (central review). Secondary end points were overall response rate, safety, and tolerability.ResultsAmong 302 patients enrolled in RADIANT-4, 46 were included in the East Asian subgroup (everolimus, n=28; placebo, n=18) analysis. Everolimus was associated with an 82% reduction in the relative risk of disease progression or death (HR 0.18, 95% CI 0.09–0.38). The median PFS (central review) in this subgroup was 11.2 months with everolimus vs 3.1 months with placebo. Adverse events (AEs) occurred in all 28 patients treated with everolimus and ten patients receiving placebo. The majority of these AEs were grade 1 or 2. Most commonly reported ($30% of incidence) drug-related AEs of any grade included stomatitis (75%, n=21) and rash (43%, n=12) in the everolimus arm.ConclusionEverolimus demonstrated a clinically meaningful PFS benefit in the East Asian population. The safety findings were consistent with the known safety profile of everolimus. These results support the use of everolimus in the East Asian population with advanced, nonfunctional NETs of GI or lung origin.

Asian Subgroup Analysis - Denosumab Vs Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Double-Dummy, Randomized Controlled Phase 3 Study

Introduction: Denosumab is a monoclonal antibody targeting receptor activator of nuclear factor-kappa B ligand (RANKL) that has been shown to reduce skeletal-related events (SREs) associated with bone lesions in patients with multiple myeloma. Results from the full primary analysis of an international, double-blind, double-dummy, randomized controlled phase 3 (20090482) study that assessed the efficacy and safety of denosumab vs zoledronic acid for preventing SREs in patients with multiple myeloma (MM) indicated that denosumab was non-inferior to zoledronic acid for time to SREs. Here we present a sub-analysis to evaluate efficacy and safety outcomes in a subgroup of Asian patients enrolled in the 20090482 study.Methods: Adult patients from Asian countries with newly diagnosed MM and ≥1 documented lytic bone lesion were included in this analysis. Patients received subcutaneous denosumab (120 mg) plus intravenous placebo or intravenous zoledronic acid (4 mg) plus subcutaneous placebo in 4-week cycles. The primary endpoint was time to first on-study SRE; the incidence of adverse events (AEs) by preferred term was also examined.Results: Overall, 196 Asian patients (denosumab, n=103; zoledronic acid, n=93) were included in this analysis. Patient demographics were generally well balanced between groups. Median (interquartile range [IQR]) number of months on study was 17.5 (9.8-30.2) for the denosumab group and 20.2 (13.1-29.2) for the zoledronic acid group. Median (IQR) cumulative drug exposure was 15.9 (8.5-24.0) months for denosumab and 17.4 (9.1-26.7) months for zoledronic acid. Fewer patients in the denosumab group developed first on-study SRE compared with the zoledronic acid group; the crude incidence of SREs at the primary analysis cutoff was 38.8% in the denosumab group and 50.5% in the zoledronic acid group. Median (95% CI) time in months to first on-study SRE was not reached (11.2-not reached) for the denosumab group and 12.3 (3.1-not reached) for the zoledronic acid group (hazard ratio [HR], 0.77; 95% CI, 0.48-1.26; Figure 1). Overall, all patients (100%) experienced ≥1 treatment-emergent AE; the AEs reported in ≥20% of patients in either treatment arm are presented in Table 1. The most common AEs reported in either subgroup (denosumab, zoledronic acid) were diarrhea (51.0%, 51.1%), nausea (42.2%, 46.7%), pyrexia (38.2%, 41.3%), upper respiratory tract infection (37.3%, 40.2%), and constipation (33.3%, 31.5%). Renal toxicity (preferred terms of blood creatinine increased, renal failure, urine output decreased, acute kidney injury, renal impairment, and blood urea decreased) occurred in 9 of 102 (8.8%) patients in the denosumab group and 20 of 92 (21.7%) patients in the zoledronic acid group. Adjudicated osteonecrosis of the jaw was reported in 7 (6.9%) patients in the denosumab group and 5 (5.4%) patients in the zoledronic acid group. Hypocalcemia was reported in 19 (18.6%) patients in the denosumab group and 17 (18.5%) patients in the zoledronic acid group.Conclusion: Results from this Asian subgroup analysis were comparable to those of the full analysis set. In addition, in this analysis there were numerically fewer patients in the denosumab arm that developed a first on-study SRE compared with those in the zoledronic acid arm, and the time to first on-study SRE had a trend favoring the denosumab-treated patients. The AE profiles for denosumab and zoledronic acid in the Asian subgroup were comparable to those observed in the full primary analysis, with renal toxicity similarly reported to be higher in the zoledronic acid group. Overall, this analysis supports that denosumab may be an additional treatment option for the standard of care for Asian patients with newly diagnosed MM with bone disease. [Display omitted] DisclosuresChng:Merck: Research Funding; Aslan: Research Funding; Celgene: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Amgen: Consultancy, Honoraria, Other: Travel, accommodation, expenses. Chang:BMS: Consultancy, Speakers Bureau; AbbVie: Consultancy; Janssen: Consultancy, Speakers Bureau; Celgene: Consultancy; Takeda: Consultancy; Roche: Consultancy, Speakers Bureau; Novarits: Consultancy, Speakers Bureau. Wong:Amgen: Consultancy, Research Funding, Speakers Bureau; Bayer: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Archigen: Research Funding; Baxalta: Research Funding; Pfizer: Research Funding; Apellis: Research Funding; Roche: Research Funding; Boehringer: Research Funding; Ingelheim: Research Funding; AbbVie: Research Funding; Alexion: Consultancy; Astellas: Speakers Bureau. Shimizu:Amgen Inc.: Other: Non-remunerative Position of Influence, Denosumab 20090482 Global Steering Committee Member; Fujimoto Pharmacuetical Corp: Consultancy; Daiichi-Sankyo, Co., Ltd: Consultancy. Gao:Amgen Asia Holding Limited: Employment, Equity Ownership. Glennane:Amgen: Employment, Equity Ownership. Guan:Amgen: Employment, Equity Ownership.

PDB62 - COST-EFFECTIVENESS ANALYSIS OF EMPAGLIFLOZIN IN JAPAN BASED ON RESULTS FROM THE SUBGROUP ANALYSIS OF ASIAN PATIENTS IN THE EMPA-REG OUTCOME TRIAL

We assessed the cost-effectiveness of empagliflozin in Japan based on the Asian subgroup analysis of the EMPA-REG OUTCOME trial. In the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of cardiovascular (CV) and renal events in patients with type 2 diabetes and established CV disease. Cost-effectiveness analysis based on the overall population of the EMPA-REG OUTCOME trial was reported previously by using lifetime discrete event simulation model. The same modeling frame was adapted to evaluate the cost-effectiveness of treatment with empagliflozin added to standard of care (SoC) compared to SoC in Japan. The time to relevant clinical events and the hazard ratios were derived from an Asian subgroup analysis of the EMPA-REG OUTCOME trial. The costs for each event were estimated from Japanese medical claims data. Direct medical cost, life expectancy and quality-adjusted life years (QALYs) were calculated from a payers’ perspective. Treatment with empagliflozin was estimated to increase life expectancy by 3.9 year and 2.1 QALYs while total cost increased by 814,764 yen (6,267 € at an exchange rate of 1 €=130 yen) compared to treatment with SoC. The incremental cost-effectiveness ratio (ICER) was 384,636 yen/QALY (2,959 €/QALY). In the sensitivity analysis, there was no case which was in excess of the reference value of ICER in the pilot introduction for price revision in Japan, 5 million yen/QALY (38,462 €/QALY). Based on the Asian subgroup analysis of the EMPA-REG OUTCOME trial, our results suggest that empagliflozin is highly cost-effective compared with SoC in Japan.