Tumor and plasma biomarker analysis from the randomized controlled phase II trial (RCT) of tivantinib in second-line hepatocellular carcinoma (HCC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 197-197 ◽  
Author(s):  
Lorenza Rimassa ◽  
Giovanni Abbadessa ◽  
Nicola Personeni ◽  
Camillo Porta ◽  
Ivan Borbath ◽  
...  
Keyword(s):  
Second Line ◽  
Phase 3 ◽  
Randomized Controlled ◽  
Biomarker Analysis ◽  
Arq 197 ◽  
Intent To Treat ◽  
Changes Over Time ◽  
Treat Population ◽  
Clinical Trial Information ◽  
Over Time

197 Background: Tivantinib, an oral MET inhibitor, showed activity in patients (pts) MET-High at immunohistochemistry (IHC) in randomized, placebo controlled studies in HCC, NSCLC, CRC, and prostate cancer. ARQ 197-215 was a RCT of tivantinib in second-line HCC. The study randomized 107 pts 2:1 to tivantinib capsules or placebo, reached the primary endpoint of time to progression in the intent-to-treat population and the pre-specified secondary efficacy endpoints, including OS, in MET-High pts. Tumor MET was also found to be a strong independent prognostic factor. This analysis aims to study prognostic and predictive value of tumor and circulating biomarkers. Methods: Circulating MET, HGF, and AFP were centrally analyzed by ELISA and median values were used as cut-offs to determine High or Low status except for AFP, where the 75th percentile was also used. Tumor MET was centrally analyzed and considered High if staining was >2+ in >50% of cells at IHC. Results: Circulating MET was prognostic (N=102; OS: 4.6 vs 8.9 months in High vs Low, HR=0.61, p=0.023) and trended towards predicting tivantinib’s activity. MET was also a pharmacodynamic marker: pts on tivantinib with a MET reduction over time survived longer; MET was reduced in pts stable on tivantinib but not on placebo. Circulating HGF was prognostic (N=102; OS: 5.0 vs 9.0 months in High vs Low, HR=0.6, p=0.02) and changes over time correlated with outcome. AFP by the 75th percentile was prognostic (N=104; OS: 3.0 vs 7.9 months in High vs Low, HR=0.36, p<0.0001). Median IHC score (H-Score) was 175 for tumor MET-High, 40 for MET-Low pts (N=77). MET was highly expressed in 40% of biopsies taken before and in 82% of biopsies taken after sorafenib. A significant interaction between tivantinib and tumor MET in terms of OS was observed (p=0.039). No biomarker except for tumor MET was predictive of response to tivantinib. Conclusions: A clear prognostic value was found for circulating MET, HGF, and AFP by the 75th percentile. Tumor MET was highly prognostic and predictive. IHC results on over 900 tumor samples analyzed in the ongoing METIV-HCC phase 3 study will also be presented. Clinical trial information: NCT00988741.

Behavioral and Self-Concept Changes After Six Months of Enuresis Treatment: A Randomized, Controlled Trial

PEDIATRICS ◽  
2000 ◽  
Vol 105 (Supplement_3) ◽  
pp. 935-940 ◽  
Author(s):  
Sally Longstaffe ◽  
Michael E. K. Moffatt ◽  
Jeanne C. Whalen
Keyword(s):  
Randomized Controlled Trial ◽  
Interaction Effect ◽  
Nocturnal Enuresis ◽  
Controlled Trial ◽  
Attention Problems ◽  
Self Concept ◽  
City Hospital ◽  
Randomized Controlled ◽  
Changes Over Time ◽  
Over Time

Background. Previous studies have suggested changes in self-concept with successful treatment of primary nocturnal enuresis (PNE), but behavioral changes have not been reported as a consistent associated finding. Objective. To determine if self-concept and behavior change after 6 months of treatment of monosymptomatic PNE by conditioning alarm or desmopressin acetate (DDAVP). Design. Randomized, controlled trial in an inner-city hospital clinic. Subjects were 182 children referred or recruited through media publicity, randomly assigned both to 1 of 8 pediatricians and 1 of 3 treatment groups (alarm, DDAVP, or placebo). Included were children &gt;7 years old with PNE, no daytime symptoms, bladder capacity &gt;50% expected, and wetting &gt;3 times a week. Excluded were children with central nervous system disorders or developmental delays, and those currently on DDAVP or alarm. Subjects completed thePiers-Harris Children's Self-Concept Scale and Harter's Perceived Competence Scale for Children (PCSC) at initial visit and after 6 months of treatment. Parents completed the Achenbach Child Behavior Checklist (CBCL) at the same times. Results. After 6 months of treatment the Piers-Harris total score showed a highly significant treatment by period interaction effect for DDAVP, a significant effect for alarm, and no effect for placebo. For children who achieved 75% dryness the CBCL showed a treatment by improvement interaction effect that was highly significant for DDAVP and placebo with no effect for alarm. For the PCSC there were no treatment or outcome interaction effects. After 6 months of treatment there were significant changes over time unrelated to outcome or treatment in the Piers-Harris Subscales and in the CBCL Internalizing and Externalizing Scores, and the Social Thought and Attention Problems Subscales. The PCSC was more stable with no changes in total score, and positive changes over time in only 2 Subscales, Scholastic and Social. Conclusion. Children's self-concept improved with the type of treatment and amount of success. Parents' perceptions of behavior improve with type of treatment and amount of success. Children rate their self-concept and some physical attributes better after treatment with any of DDAVP, alarm, or placebo regardless of outcome. Frequent follow-up with emotional support and encouragement appear to be important components of an efficacious intervention for children with nocturnal enuresis.

scholarly journals The Efficacy and Safety of Eravacycline in the Treatment of Complicated Intra-Abdominal Infections: A Systemic Review and Meta-Analysis of Randomized Controlled Trials

2019 ◽  
Vol 8 (6) ◽  
pp. 866 ◽  
Author(s):  
Shao-Huan Lan ◽  
Shen-Peng Chang ◽  
Chih-Cheng Lai ◽  
Li-Chin Lu ◽  
Chien-Ming Chao
Keyword(s):  
Adverse Event ◽  
Clinical Cure ◽  
Clinical Cure Rate ◽  
Clinical Failure ◽  
Efficacy And Safety ◽  
Cure Rate ◽  
Randomized Controlled ◽  
Evaluable Population ◽  
Intent To Treat ◽  
Treat Population

This study aims to assess the clinical efficacy and safety of eravacycline for treating complicated intra-abdominal infection (cIAI) in adult patients. The PubMed, Web of Science, EBSCO, Cochrane databases, Ovid Medline, Embase, and ClinicalTrials.gov were searched up to May 2019. Only randomized controlled trials (RCTs) that evaluated eravacycline and other comparators for the treatment of cIAI were included. The primary outcome was the clinical cure rate at the test-of-cure visit based on modified intent-to-treat population, microbiological intent-to-treat population, clinically evaluable population, and microbiological evaluable population, and the secondary outcomes were clinical failure rate and the risk of adverse event. Three RCTs were included. Overall, eravacycline had a clinical cure rate (88.7%, 559/630) at test-of-cure in modified intent-to-treat population similar to comparators (90.1%, 492/546) in the treatment of cIAIs (risk ratio (RR), 0.99; 95% confidence interval (CI), 0.95–1.03; I2 = 0%, Figure 3). In the microbiological intent-to-treat, clinically evaluable, and microbiological evaluable populations, no difference was found between eravacycline and comparators in terms of clinical cure rate at test-of-cure (microbiological intent-to-treat population, RR, 0.99; 95% CI, 0.95–1.04; I2 = 0%, clinically evaluable population, RR, 1.00; 95% CI, 0.97–1.03; I2 = 0%, microbiological evaluable population, RR, 0.98; 95% CI, 0.95–1.02; I2 = 0%). In addition, eravacycline had clinical failure rate similar to comparators at test-of-cure in modified intent-to-treat population (RR, 1.01; 95% CI, 0.61–0.69; I2 = 0%), microbiological intent-to-treat population (RR, 1.34; 95% CI, 0.77–2.31; I2 = 16%), clinically evaluable population (RR, 1.03; 95% CI, 0.61–1.76; I2 = 0%), and microbiological evaluable population (RR, 1.32; 95% CI, 0.75–2.32; I2 = 10%). Although eravacycline was associated with higher risk of treatment-emergent adverse event than comparators (RR, 1.34; 95% CI, 1.13–1.58; I2 = 0%), no significant differences were found between eravacycline and comparators for the risk of serious adverse event (RR, 1.04; 95% CI, 0.65–1.65; I2 = 0%), discontinuation of study drug because of adverse event (RR, 0.68; 95% CI, 0.23–1.99; I2 = 13%), and all-cause mortality (RR, 1.09; 95% CI, 0.41–2.9; I2 = 28%). In conclusion, the clinical efficacy of eravacycline is as high as that of the comparator drugs in the treatment of cIAIs and this antibiotic is as well tolerated as the comparators.

Expanded analyses of napoli-1: Phase 3 study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 234-234 ◽  
Author(s):  
Li-Tzong Chen ◽  
Daniel D. Von Hoff ◽  
Chung-Pin Li ◽  
Andrea Wang-Gillam ◽  
Gyorgy Bodoky ◽  
...  
Keyword(s):  
Sensitivity Analyses ◽  
Open Label ◽  
Phase 3 ◽  
Open Label Study ◽  
Prior Therapy ◽  
Previously Treated ◽  
Grade 3 ◽  
Intent To Treat ◽  
To Receive ◽  
Clinical Trial Information

234 Background: MM-398 is a nanoliposomal encapsulation of irinotecan. OS in the ITT population was significantly longer with MM-398+5FU/LV over 5FU/LV alone, and the most frequent grade 3+ AEs included neutropenia, fatigue, and GI effects (diarrhea and vomiting). Expanded, pre-specified analyses of the Phase 3 study are presented. Methods: Patients (n=417) with mPAC previously treated with gemcitabine-based therapy, were randomized 1:1:1 in an open-label study to receive: (A) MM-398 (120 mg/m2 IV over 90 min) q3w; (B) 5FU (2,000 mg/m2 over 24 h) plus racemic leucovorin (LV) (200 mg/m2 over 30 min) x 4w followed by 2w rest; or (C) combination of MM-398 (80 mg/m2 IV over 90 min) prior to 5FU (2,400 mg/m2 over 46 h) and racemic LV (400 mg/m2 over 30 min) q2w. The primary endpoint was OS. The Intent To Treat (ITT) population included all randomized patients; the Per Protocol (PP) population included patients who received at least 80% of the target dose in the first 6 weeks and did not violate any inclusion/exclusion criteria. Results: Analysis of the PP populations confirmed the favorable OS, which was also reflected by the PFS, ORR and CA19-9 levels, of the combination MM-398+5FU/LV arm over the control 5FU/LV arm. The MM-398 monotherapy arm did not show a statistically significant improvement in OS compared with the control arm. Analysis of subgroups, based on pretreatment characteristics including stage at diagnosis, time since initial histological diagnosis, prior lines of therapy, time since last prior therapy, and CA19-9 levels, consistently favored OS for the MM-398+5FU/LV arm over the 5FU/LV arm. Conclusions: Expanded analysis of the PP population and sensitivity analyses support the favorability of MM-398+5FU/LV over 5FU/LV, with a manageable safety profile. Clinical trial information: NCT01494506. [Table: see text]

scholarly journals Covid-19 in the Phase 3 Trial of mRNA-1273 During the Delta-variant Surge

2021 ◽  
Author(s):  
Lindsey R. Baden ◽  
Hana M. El Sahly ◽  
Brandon Essink ◽  
Dean Follmann ◽  
Kathleen M. Neuzil ◽  
...  
Keyword(s):  
Incidence Rates ◽  
Open Label ◽  
Phase 3 ◽  
Genetic Sequencing ◽  
The Us ◽  
Open Label Phase ◽  
Genetic Sequences ◽  
Intent To Treat ◽  
Lab Test ◽  
Treat Population

AbstractBackgroundFollowing emergency use authorization in December 2020, the Coronavirus Efficacy (COVE) trial was amended to an open-label phase, where participants were unblinded and those randomized to placebo were offered vaccination. Emergence of the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with increased incidences of coronavirus disease 2019 (Covid-19) among unvaccinated and vaccinated persons. This exploratory analysis evaluated the incidence and genetic sequences of Covid-19 cases in the ongoing COVE trial during the open-label phase, with a focus on July-August 2021, when delta-variants surged in the US.MethodsCovid-19 cases were identified in participants initially randomized to mRNA-1273 (vaccinated from July-December 2020) and those initially randomized to the placebo (vaccinated December 2020-April 2021) who received at least one dose and were SARS-CoV-2-negative at baseline in the modified-intent-to-treat population were analyzed. Included were Covid-19 cases occurring after 26-Mar-2021 with positive RT-PCR results in nasopharyngeal samples (central lab test) and reported Covid-19 symptoms. Genetic sequencing of Covid-19 cases was also performed.ResultsThere were 14,746 participants in the earlier mRNA-1273 (mRNA-1273e) group and 11,431 in the later placebo-mRNA1273 (mRNA-1273p) group. Covid-19 cases increased from the start of the open-label phase to July-August 2021. During July and August, 162 Covid-19 cases occurred in the mRNA-1273e group and 88 in the mRNA-1273p group. Of the cases sequenced, 144/149 [97%]) in the mRNA-1273 and 86/88 (99%) in the mRNA-1273p groups were attributed to delta. The incidence rate of Covid-19 was lower for the mRNA-1273p (49.0/1000 person-years) versus mRNA-1273e (77.1/1000 person-years) group [36.4% (95% CI 17.1%-51.5%) reduction]. There were fewer severe Covid-19 cases in the mRNA-1273p (6; 6.2/1000 person-years) than mRNA-1273e (13; 3.3/1000 person-years) [46.0% (95% CI −52.4%-83.2%) reduction]. Three Covid-19 related hospitalizations occurred with two resulting deaths in the mRNA-1273e group.ConclusionIncidence rates of Covid-19 and severe Covid-19 were lower during the months when delta was the dominant variant (July/August 2021) among COVE participants vaccinated more recently. Analysis of COVID-19 cases from the open-label phase of the COVE study is ongoing.

scholarly journals O-0009 Second Line Therapy in Hepatocellular Carcinoma (HCC): A Randomized Controlled Phase 2 Trial (RCT) with Tivantinib (ARQ 197)

2012 ◽  
Vol 23 ◽  
pp. iv8
Author(s):  
Camillo Porta ◽  
Ivan Borbath ◽  
Lorenza Rimassa ◽  
Bruno Daniele ◽  
Stefania Salvagni ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Second Line ◽  
Phase 2 ◽  
Second Line Therapy ◽  
Randomized Controlled ◽  
Phase 2 Trial ◽  
Line Therapy ◽  
Arq 197

scholarly journals Ceftolozane/tazobactam versus meropenem in patients with ventilated hospital-acquired bacterial pneumonia: subset analysis of the ASPECT-NP randomized, controlled phase 3 trial

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Jean-François Timsit ◽  
Jennifer A. Huntington ◽  
Richard G. Wunderink ◽  
Nobuaki Shime ◽  
Marin H. Kollef ◽  
...  
Keyword(s):  
Bacterial Pneumonia ◽  
Controlled Trial ◽  
Multivariable Logistic Regression Analysis ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Intention To Treat ◽  
Randomized Controlled ◽  
Hospital Acquired ◽  
The Impact ◽  
Treat Population

Abstract Background Ceftolozane/tazobactam is approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) at double the dose approved for other infection sites. Among nosocomial pneumonia subtypes, ventilated HABP (vHABP) is associated with the lowest survival. In the ASPECT-NP randomized, controlled trial, participants with vHABP treated with ceftolozane/tazobactam had lower 28-day all-cause mortality (ACM) than those receiving meropenem. We conducted a series of post hoc analyses to explore the clinical significance of this finding. Methods ASPECT-NP was a multinational, phase 3, noninferiority trial comparing ceftolozane/tazobactam with meropenem for treating vHABP and VABP; study design, efficacy, and safety results have been reported previously. The primary endpoint was 28-day ACM. The key secondary endpoint was clinical response at test-of-cure. Participants with vHABP were a prospectively defined subgroup, but subgroup analyses were not powered for noninferiority testing. We compared baseline and treatment factors, efficacy, and safety between ceftolozane/tazobactam and meropenem in participants with vHABP. We also conducted a retrospective multivariable logistic regression analysis in this subgroup to determine the impact of treatment arm on mortality when adjusted for significant prognostic factors. Results Overall, 99 participants in the ceftolozane/tazobactam and 108 in the meropenem arm had vHABP. 28-day ACM was 24.2% and 37.0%, respectively, in the intention-to-treat population (95% confidence interval [CI] for difference: 0.2, 24.8) and 18.2% and 36.6%, respectively, in the microbiologic intention-to-treat population (95% CI 2.5, 32.5). Clinical cure rates in the intention-to-treat population were 50.5% and 44.4%, respectively (95% CI − 7.4, 19.3). Baseline clinical, baseline microbiologic, and treatment factors were comparable between treatment arms. Multivariable regression identified concomitant vasopressor use and baseline bacteremia as significantly impacting ACM in ASPECT-NP; adjusting for these two factors, the odds of dying by day 28 were 2.3-fold greater when participants received meropenem instead of ceftolozane/tazobactam. Conclusions There were no underlying differences between treatment arms expected to have biased the observed survival advantage with ceftolozane/tazobactam in the vHABP subgroup. After adjusting for clinically relevant factors found to impact ACM significantly in this trial, the mortality risk in participants with vHABP was over twice as high when treated with meropenem compared with ceftolozane/tazobactam. Trial registration clinicaltrials.gov, NCT02070757. Registered 25 February, 2014, clinicaltrials.gov/ct2/show/NCT02070757.

scholarly journals Characterization of Tumor Size Changes Over Time from the Phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (Select)

2014 ◽  
Vol 25 ◽  
pp. iv354 ◽  
Author(s):  
B. Robinson ◽  
M. Schlumberger ◽  
L.J. Wirth ◽  
C. Dutcus ◽  
B.D.L. Heras ◽  
...  
Keyword(s):  
Tumor Size ◽  
Phase 3 ◽  
Changes Over Time ◽  
Over Time

Major impact of personalized dosimetry using 90Y loaded glass microspheres SIRT in HCC: Final overall survival analysis of a multicenter randomized phase II study (DOSISPHERE-01).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 516-516 ◽  
Author(s):  
Etienne Garin ◽  
Lambros Tzelikas ◽  
Boris Guiu ◽  
Julia Chalaye ◽  
Julien Edeline ◽  
...  
Keyword(s):  
Overall Survival ◽  
Index Lesion ◽  
Phase 2 Trial ◽  
Randomized Phase Ii ◽  
Safety Population ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Intent To Treat ◽  
Treat Population ◽  
Clinical Trial Information

516 Background: 90Y loaded microsphere SIRT (radioembolization) is a treatment option in advanced HCC. However, no personalized dosimetric endpoints are currently used. The goal of this study was to compare the efficacy of 90Y loaded glass microsphere SIRT in HCC using a standard versus a personalized dosimetric approach. Methods: DOSISPHERE-01 was a multicenter, randomized phase 2 trial in unresectable HCC patients with at least one tumor ≥7cm. Treatment arm was randomly assigned (1:1) to standard dosimetry arm (SDA), with a goal to deliver 120±20Gy to the treated volume or to personalized dosimetry arm (PDA) with a goal to deliver at least 205Gy to the index lesion. The primary endpoint was the response rate (RR) of the index lesion according to EASL criteria. Secondary endpoints included dose response evaluation, safety and overall survival (OS). Results: Sixty HCC patients were randomized (PDA 31, SDA 29, intent to treat population-ITTP-), and 56 treated (28 in each arm). RR was significantly increased in the PDA versus the SDA, in the ITTP, respectively 64.5% versus 31% (p=0.0095) as in the safety population -SP- (treatment effectively received, personalized 35, standard 21), respectively 74.3% versus 14.3% (p<0.0001). Median OS was significantly increased in the PDA versus the SDA, in the ITTP, respectively 26.7m (CI 95%:11.7-NR) versus 10.6m (CI 95%:6-16.8), p=0.0096, HR=0.421 (95%CI:0.215-0.826), p=0.0119, as in the SP, respectively 26.7m (CI 95%:11.7- NR) versus 9.5m (CI 95%:4.8-14.9), p=0.0015, HR=0.342 (95%CI:0.171-0.683), p=0.0023. Median OS was 26.7m (CI 95%:13.5-NR) versus 6.0m (CI 95%:3.8-14.9) for the patients who received a tumor dose ≥205 Gy or <205 Gy respectively, p=0.0106, HR=0.336 (95%CI:0.154-0.735), p=0.0063. Treatment-related clinically relevant hepatic ≥grade 3 AEs were observed in 5.7% and 14.2% of the patients of the PDA and SDA arms, respectively, (p=ns). Conclusions: MAA SPECT/CT based personalized dosimetry is safe and dramatically increased RR and OS of HCC patients. These results question the interpretation of all phase 3 trials of SIRT designed without personalized dosimetry in HCC. Clinical trial information: 2015-A00894-45.

scholarly journals Evaluating Vaccine Efficacy Against SARS-CoV-2 Infection

2021 ◽  
Author(s):  
Dan-Yu Lin ◽  
Yu Gu ◽  
Donglin Zeng ◽  
Holly E. Janes ◽  
Peter B. Gilbert
Keyword(s):  
Clinical Trials ◽  
Vaccine Efficacy ◽  
Diagnostic Tests ◽  
Time Varying ◽  
Rt Pcr ◽  
Phase 3 ◽  
Numerical Studies ◽  
Community Transmission ◽  
Changes Over Time ◽  
Over Time

AbstractAlthough interim results from several large placebo-controlled phase 3 trials demonstrated high vaccine efficacy (VE) against symptomatic COVID-19, it is unknown how effective the vaccines are in preventing people from becoming asymptomatically infected and potentially spreading the virus unwittingly. It is more difficult to evaluate VE against SARS-CoV-2 infection than against symptomatic COVID-19 because infection is not observed directly but rather is known to occur between two antibody or RT-PCR tests. Additional challenges arise as community transmission changes over time and as participants are vaccinated on different dates because of staggered enrollment or crossover before the end of the study. Here, we provide valid and efficient statistical methods for estimating potentially waning VE against SARS-CoV-2 infection with blood or nasal samples under time-varying community transmission, staggered enrollment, and blinded or unblinded crossover. We demonstrate the usefulness of the proposed methods through numerical studies mimicking the BNT162b2 phase 3 trial and the Prevent COVID U study. In addition, we assess how crossover and the frequency of diagnostic tests affect the precision of VE estimates.SummaryWe show how to estimate potentially waning efficacy of COVID-19 vaccines against SARS-CoV-2 infection using blood or nasal samples collected periodically from clinical trials with staggered enrollment of participants and crossover of placebo recipients.

ABSOLUTE: A phase 3 trial of nanoparticle albumin-bound paclitaxel (nab-PTX) versus solvent-based paclitaxel (sb-PTX) in patients with pre-treated advanced gastric cancer (AGC)—Efficacy and QOL results.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4010-4010
Author(s):  
Keisuke Koeda ◽  
Kohei Shitara ◽  
Atsuo Takashima ◽  
Kazumasa Fujitani ◽  
Hironori Tsujimoto ◽  
...  
Keyword(s):  
Response Rate ◽  
Primary Objective ◽  
Favorable Effect ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Phase 3 ◽  
Best Response ◽  
To Receive ◽  
Clinical Trial Information

4010 Background: Sb-PTX is a standard second-line treatment for patients (pts) with AGC. Nab-PTX was developed to avoid the toxicities with use of solvents in sb-PTX and potentially improve efficacy. Based on ABSOLUTE trial, we conducted the additional analysis to evaluate the efficacy and QOL of nab-PTX and sb-PTX. Methods: Pts who were refractory to a fluoropyrimidine-containing first-line treatment were randomly assigned (1:1:1) to receive intravenous q3w nab-PTX (260 mg/m2) on day 1 of a 21-day cycle, and q1w nab-PTX (100 mg/m2) or q1w sb-PTX (80 mg/m2) on days 1, 8, and 15 of a 28-day cycle. The primary objective was to evaluate whether q3w nab-PTX and q1w nab-PTX were non-inferior to q1w sb-PTX in terms of overall survival (OS). Tumor shrinkage at 8 weeks and at the time of the best response were also investigated. For the QOL analysis, EQ-5D score were collected at baseline and every 8 weeks during the first 24 weeks, and thereafter at every 24 weeks. Time to deterioration of EQ-5D score was compared between each arm as a minimally important difference of 0.05. Results: 741 pts were randomly assigned to q3w nab-PTX, q1w nab-PTX, or q1w sb-PTX. Median OS (months) were 10.3, 11.1, and 10.9, respectively. Q1w nab-PTX was non-inferior to q1w sb-PTX (hazard ratio 0.97, 97.5% CI 0.76-1.23; non-inferiority one-sided p = 0.0085), whereas q3w nab-PTX was not non-inferior to q1w sb-PTX (1.06, 95% CI 0.87-1.31; non-inferiority one-sided p = 0.062).The response rate of target lesions at 8 weeks and at the time of the best response (%) were 22.1 and 27.7 for q3w nab-PTX, 28.2 and 34.9 for q1w nab-PTX, and 18.0 and 25.6 for q1w sb-PTX. Median time to deterioration of EQ-5D score (months) were 2.1 in q3w nab-PTX, 3.8 in q1w nab-PTX, and 3.7 in q1w sb-PTX. Conclusions: Q1w nab-PTX was non-inferior to q1w sb-PTX in terms of OS. In addition, q1w nab-PTX showed favorable effect in comparison with q1w sb-PTX in terms of response rate of target lesions and time at best response. QOL was similar between q1w nab-PTX and q1w sb-PTX. These results suggest that q1w nab-PTX is a useful second-line treatment for pts with AGC. Clinical trial information: 132059.

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