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The efficacy and safety of olaratumab plus nabpaclitaxel and gemcitabine in treatment-naïve participants with metastatic pancreatic ductal adenocarcinoma was evaluated. An initial phase 1b dose-escalation trial was conducted to determine the olaratumab dose for the phase 2 trial, a randomized, double-blind, placebo-controlled trial to compare overall survival (OS) in the olaratumab arm vs. placebo arms. In phase 1b, 22 participants received olaratumab at doses of 15 and 20 mg/kg with a fixed dose of nabpaclitaxel and gemcitabine. In phase 2, 159 participants were randomized to receive olaratumab 20 mg/kg in cycle 1 followed by 15 mg/kg in the subsequent cycles (n = 81) or the placebo (n = 78) on days 1, 8, and 15 of a 28-day cycle, plus nabpaclitaxel and gemcitabine. The primary objective of the trial was not met, with a median OS of 9.1 vs. 10.8 months (hazard ratio [HR] = 1.05; 95% confidence interval [CI]: 0.728, 1.527; p = 0.79) and the median progression-free survival (PFS) was 5.5 vs. 6.4 months (HR = 1.19; 95% CI: 0.806, 1.764; p = 0.38), in the olaratumab vs. placebo arms, respectively. The most common treatment-emergent adverse event of any grade across both arms was fatigue. Olaratumab plus chemotherapy failed to improve the OS or PFS in participants with metastatic PDAC. There were no new safety signals.

Gemcitabine plus docetaxel is an effective treatment regimen for advanced soft tissue sarcomas (STSs). However, the prognosis for patients remains poor, and thus there is an urgent medical need for novel and effective therapies to improve long-term outcomes. The aim of the ANNOUNCE 2 trial was to explore the addition of olaratumab (O) to gemcitabine (G) and docetaxel (D) for advanced STS. Adults with unresectable locally advanced/metastatic STS, ≤2 prior lines of systemic therapy, and ECOG PS 0-1 were eligible. In Phase 2, patients were randomized 1:1 from two cohorts (O-naïve and O-pretreated) to 21-day cycles of olaratumab (20 mg/kg Cycle 1 and 15 mg/kg other cycles, Days 1 and 8), gemcitabine (900 mg/m2, Days 1 and 8), and docetaxel (75 mg/m2, Day 8). The primary objective was overall survival (OS) in the O-naïve population (α level = 0.20). Secondary endpoints included OS (O-pretreated), other efficacy parameters, patient-reported outcomes, safety, pharmacokinetics, and immunogenicity. A total of 167 and 89 patients were enrolled in the O-naïve and O-pretreated cohorts, respectively. Baseline patient characteristics were well balanced. No statistically significant difference in OS was observed between the investigational vs. control arm for either cohort (O-naïve cohort: HR = 0.95 (95% CI: 0.64-1.40), p = 0.78, median OS, 16.8 vs. 18.0 months; O-pretreated cohort: HR = 0.67 (95% CI: 0.39-1.16), p = 0.15, median OS 19.8 vs. 17.3 months). Safety was manageable across treatment arms. There was no statistically significant difference in the primary endpoint of OS between the two arms in the O-naïve population, and therefore based on hierarchical evaluation no other outcomes in this study can be considered statistically significant. No new safety signals were observed.

PurposeLiver metastasis (LM) is reported in approximately 40% of patients with advanced/metastatic gastric/gastroesophageal junction adenocarcinoma (metastatic esophagogastric adenocarcinoma; mGEA) and is associated with a worse prognosis. This post-hoc analysis from the RAINBOW trial reported the efficacy, safety, and biomarker outcomes of ramucirumab and paclitaxel combination treatment (RAM+PAC) in patients with (LM+) and without (LM-) LM at baseline.Materials and methodsPatients (n=665) were randomly assigned on a 1:1 basis to receive either RAM+PAC (LM+: 150, LM-: 180) or placebo and paclitaxel (PL+PAC) (LM+: 138, LM-: 197). The overall survival (OS) and progression-free survival (PFS) were evaluated using stratified Kaplan-Meier and Cox regression models. The correlation of dichotomized biomarkers (VEGF-C, D; VEGFR-1,2) with efficacy in the LM+ versus LM- subgroups was analyzed using the Cox regression model with reported interaction P-values.ResultsThe presence of LM was associated with earlier progression than those without LM, particularly in patients receiving PL+PAC (hazard ratio [HR], 1.68). RAM+PAC treatment improved OS and PFS irrespective of LM status but showed greater improvement in LM+ than that in LM- (OS HR, 0.71 [LM+] vs. 0.88 [LM-]; PFS HR, 0.47 [LM+] vs. 0.76 [LM-]). Treatment-emergent adverse events were similar between patients with and without LM. No predictive relationship was observed between biomarker levels (VEGF-C, D; VEGFR-1,2) and efficacy outcome (OS, PFS) (all interaction P-values >0.05).ConclusionsRAM provided a significant benefit, irrespective of LM status; however, its effect was numerically stronger in patients with LM. Therefore, RAM+PAC is a clinically meaningful therapeutic option for patients with mGEA and LM.Trial registrationClinicalTrials.gov Identifier: NCT01170663.

Challenges for some women meeting the physical employment standards (PES) for ground close combat (GCC) roles stem from physical fitness and anthropometric characteristics. The purpose of this study was to identify the modifiable and nonmodifiable characteristics predictive of passing GCC‐based PES tasks and determine the modifiable characteristics suitable to overcome nonmodifiable limitations. 107 adults (46 women) underwent multiday testing assessing regional and total lean mass (LM), percent body fat (BF%), aerobic capacity (V̇O2peak), strength, power, and PES performance. Predictors with p‐value <0.200 were included in stepwise logistic regression analysis or binary logistic regression when outcomes among sexes were insufficient. Relative and absolute arm LM (OR: 4.617–8.522, p < 0.05), leg LM (OR: 2.463, p < 0.05), and upper body power (OR: 2.061, p < 0.05) predicted medicine ball chest throw success. Relative and absolute arm LM (OR: 3.734–11.694, p < 0.05), absolute trunk LM (OR: 2.576, p < 0.05), and leg LM (OR: 2.088, p < 0.05) predicted casualty drag success. Upper body power (OR: 3.910, p < 0.05), absolute trunk LM (OR: 2.387, p < 0.05), leg LM (OR: 2.290, p < 0.05), and total LM (OR: 1.830, p < 0.05) predicted maximum single lift success. Relative and absolute arm LM (OR: 3.488–7.377, p < 0.05), leg LM (OR: 1.965, p < 0.05), and upper body power (OR: 1.957, p < 0.05) predicted water can carry success. %BF (OR: 0.814, p = 0.007), V̇O2peak (OR: 1.160, p = 0.031), and lower body strength (OR: 1.059, p < 0.001) predicted repeated lift and carry success. V̇O2peak (OR: 1.540, p < 0.001) predicted 2‐km ruck march success. Modifiable characteristics were the strongest predictors for GCC‐based PES task success to warrant their improvement for enhancing PES performance for women. Highlights: Women in GCC roles require sufficient military‐specific physical fitness and anthropometric parameters, independent of sex, for successfully passing GCC‐based PES tasks as part of assessment testing and selection procedures for GCC roles.Passing GCC‐based PES tasks involving heavy lifting, dragging, pushing/throwing, and carrying may benefit from increased upper body (arm and trunk) and lower body lean mass and upper body power and maximal strength, whereas passing material handling tasks may benefit from lower percent body fat, greater lower body muscular strength, and higher aerobic capacity with the latter important for passing load carriage tasks.Military trainers should target modifiable characteristics, including upper body lean mass, power, and maximal strength to improve GCC‐based PES task performance in women. [ABSTRACT FROM AUTHOR]

Introduction Several challenges face the U.S. Marine Corps (USMC) and other services in their efforts to design recruit training to augment warfighter mobility and resilience in both male and female recruits as part of an integrated model. Strength and power underpin many of the physical competencies required to meet the occupational demands one might face in military. As the military considers adopting force plate technology to assess indices of strength and power, an opportunity presents itself for the use of machine learning on large datasets to deduce the relevance of variables related to performance and injury risk. The primary aim of this study was to determine whether cluster analysis on baseline strength and power data derived from countermovement jump (CMJ) and isometric mid-thigh pull (IMTP) adequately partitions men and women entering recruit training into distinct performance clusters. The secondary aim of this study is then to assess the between-cluster frequencies of musculoskeletal injury (MSKI). Materials and Methods Five hundred and sixty-five males (n  = 386) and females (n  = 179) at the Marine Corps Recruit Depots located at Parris Island and San Diego were enrolled in the study. Recruits performed CMJ and IMTP tests at the onset of training. Injury data were collected via medical chart review. Combat fitness test (CFT) and physical fitness test (PFT) results were provided to the study team by the USMC. A k -means cluster analysis was performed on CMJ relative peak power, IMTP relative peak force, and dynamic strength index. Independent sample t -tests and Cohen's d effect sizes assessed between-cluster differences in CFT and PFT performance. Differences in cumulative incidence of lower extremity %MSKIs were analyzed using Fisher's exact test. Relative risk and 95% confidence intervals (CIs) were also calculated. Results The overall effects of cluster designation on CMJ and IMTP outcomes ranged from moderate (relative peak power: d  = −0.68, 95% CI, −0.85 to −0.51) to large (relative peak force: d  = −1.69, 95% CI, −1.88 to −1.49; dynamic strength index: d  = 1.20, 95% CI, 1.02-1.38), indicating acceptable k -means cluster partitioning. Independent sample t -tests revealed that both men and women in cluster 2 (C2) significantly outperformed those in cluster 1 (C1) in all events of the CFT and PFT (P  < .05). The overall and within-gender effect of cluster designation on both CFT and PFT performance ranged from small (d  > 0.2) to moderate (d  > 0.5). Men in C2, the high-performing cluster, demonstrated a significantly lower incidence of ankle MSKI (P  = .04, RR = 0.2, 95% CI, 0.1-1.0). No other between-cluster differences in MSKI were statistically significant. Conclusions Our results indicate that strength and power metrics derived from force plate tests effectively partition USMC male and female recruits into distinct performance clusters with relevance to tactical and physical fitness using k -means clustering. These data support the potential for expanded use of force plates in assessing readiness in a cohort of men and women entering USMC recruit training. The ability to pre-emptively identify high and low performers in the CFT and PFT can aid in leadership developing frameworks for tailoring training to enhance combat and physical fitness with benchmark values of strength and power. [ABSTRACT FROM AUTHOR]

In the British Army, ground close combat roles have opened to women, however, they must pass the newly developed, gender-neutral Role Fitness Tests for Soldiers (RFT(S)). Due to physiological differences between sexes, training that optimally prepares both sexes for military occupational demands and the RFT(S) is needed. The purpose of this study was to determine the efficacy of a 12-week periodized strength and power programme with concurrent interval training on RFT(S) performance and determine if performance adaptations differed between sexes. 39 recruit-aged (18-35 yrs) participants, including 21 men (29 ± 1 yrs) and 18 women (27 ± 1 yrs), completed the study. Participants performed 3 training sessions per week that included strength and power resistance training followed by interval training. Pre- to post-training, improvements were observed for seated medicine ball throw (4.5%, p < 0.001), casualty drag (29.8%, p < 0.001), single lift (8.9%, p < 0.001), water can carry (13.8%, p = 0.012), repeated lift and carry (6.5%, p < 0.001), 2-km load carriage (7.2%, p < 0.001) and 2-km run (3.2%, p = 0.021). Pre- to post-training improvements were also observed for maximal squat (27.0%, p < 0.001), bench press (8.9%, p < 0.001) and deadlift (24.6%, p < 0.001) maximal strength, but not upper body power or aerobic capacity. No differences in RFT(S) improvements were observed between sexes, however men performed better than women in all RFT(S) and physical performance measures. Concurrent resistance and interval training improves military occupational performance in men and women; however, women may need more training than men to pass the gender-neutral RFT(S). [ABSTRACT FROM AUTHOR]

Purpose: Liver metastasis (LM) is reported in approximately 40% of patients with advanced/ metastatic gastric/gastroesophageal junction adenocarcinoma (metastatic esophagogastric adenocarcinoma; mGEA) and is associated with a worse prognosis. This post-hoc analysis from the RAINBOW trial reported the efficacy, safety, and biomarker outcomes of ramucirumab and paclitaxel combination treatment (RAM+PAC) in patients with (LM+) and without (LM−) LM at baseline. Materials and Methods: Patients (n=665) were randomly assigned on a 1:1 basis to receive either RAM+PAC (LM+: 150, LM−: 180) or placebo and paclitaxel (PL+PAC) (LM+: 138, LM−: 197). The overall survival (OS) and progression-free survival (PFS) were evaluated using stratified Kaplan–Meier and Cox regression models. The correlation of dichotomized biomarkers (VEGF-C, D; VEGFR-1,2) with efficacy in the LM+ versus LM− subgroups was analyzed using the Cox regression model with reported interaction P-values. Results: The presence of LM was associated with earlier progression than those without LM, particularly in patients receiving PL+PAC (hazard ratio [HR], 1.68). RAM+PAC treatment improved OS and PFS irrespective of LM status but showed greater improvement in LM+ than that in LM− (OS HR, 0.71 [LM+] vs. 0.88 [LM−]; PFS HR, 0.47 [LM+] vs. 0.76 [LM−]). Treatment-emergent adverse events were similar between patients with and without LM. No predictive relationship was observed between biomarker levels (VEGF-C, D; VEGFR-1,2) and efficacy outcome (OS, PFS) (all interaction P-values >0.05). Conclusions: RAM provided a significant benefit, irrespective of LM status; however, its effect was numerically stronger in patients with LM. Therefore, RAM+PAC is a clinically meaningful therapeutic option for patients with mGEA and LM. [ABSTRACT FROM AUTHOR]