Citations

Objective: Aneurysm growth is considered predictive of future rupture of intracranial aneurysms. However, it is still unknown how accurately neuroradiologists can reliably detect incremental aneurysm growth using clinical magnetic resonance imaging (MRI) imaging. The purpose of this study is to assess the agreement rate of detecting aneurysm enlargement using generally used MRI imaging modalities. Methods: Three silicone flow phantom models each with eight aneurysms of various sizes in different sites were used in this study. The aneurysm models were identical except for an incremental increase in size of the 8 aneurysms ranging from 0.4mm to 2mm. The phantoms were imaged on 1.5 tesla (T) and 3T MRI units with both time-of-flight (TOF) and contrast enhanced magnetic resonance angiography (MRA). Three independent expert neuroradiologists measured the aneurysms in a blinded fashion utilizing different measurement approaches. The individual and agreement rate among the three experts in detecting aneurysm enlargement were calculated. Results: The average detection rate of any increase in any aneurysmal dimensions was 95.7%. The detection rate for the three readers (A, B and C) was 98.0%, 96.6% and 92.7%, respectively ( P =0.22). The detection rate in each MRI modality was 91.3% using 1.5 T TOF, 97.2% using 1.5T gadolinium (Gad), 95.8% using 3.0T TOF and 97.2% using 3.0T Gad ( P =0.31). As the incremental enlargement value increased, the detection rate for aneurysm enlargement increased. Use of Gad in 1.5T improved the detection rate in small incremental enlargement (e.g. 0.4 - 1mm) of the aneurysm ( P =0.04). The locations of the aneurysms also affected detection rate for aneurysm enlargement ( P <0.0001). Conclusions: The detection rate and interobserver agreement was very high for aneurysm enlargement of 0.4mm to 2 mm. Detection rate of any increase in any aneurysmal dimensions did not depend on the choice of MRI imaging modalities and measurement protocols.

TPS4138 Background: Apatinib is an orally administered, highly selective tyrosine kinase inhibitor of VEGFR-2 that has been studied in many clinical trials, primarily in China, treating various solid tumors. Based on the results of the Chinese Phase 3 study, apatinib was approved in China for the treatment of advanced gastric cancer (GC), but apatinib has yet to be evaluated in a randomized placebo-controlled study in the rest of the world. ANGEL is a multinational, placebo controlled, Phase 3 study investigating the efficacy and safety of apatinib in advanced GC patients in North America, Europe, and Asia Pacific. Methods: Main eligibility criteria include patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction for whom at least 2 prior lines of standard chemotherapy had failed, ECOG performance status ≤ 1, and disease progression < 6 months after last chemotherapy treatment. Approximately 459 patients will be randomized in a 2:1 ratio to receive continuous 28-day cycles of apatinib 700 mg or a matched placebo daily with best supportive care until disease progression, intolerable toxicity or withdrawal of consent. Stratification factors include geographic region (Asia vs. North America/Europe), disease measurability, prior ramucirumab treatment, and treatment therapy line (3rd or 4th). Primary endpoint is overall survival (OS) in the intent-to-treat population, and secondary endpoints are progression free survival (PFS), objective response rate (ORR), disease control rate (DCR), quality of life, and safety. The primary analysis of OS will be conducted in intention-to-treat population using a stratified log-rank test at the two-sided alpha = 0.05 level of significance. If the primary analysis of OS is statistically significant, then PFS and ORR will be analyzed. All other secondary efficacy endpoints will be analyzed using two-sided tests at the alpha = 0.05 level of significance. Enrollment opened Feb 2017. Clinical trial information: NCT03042611.

4003 Background: Pembro has shown promising antitumor activity and manageable safety in a phase 1 study of pts with previously treated advanced gastric cancer. We conducted a global, multicohort, phase 2 study of pembro in pts with advanced gastric or gastroesophageal junction (G/GEJ) cancer (KEYNOTE-059;NCT02335411). Methods: Cohort 1 enrolled 259 pts, aged ≥18 y with measurable recurrent or metastatic G/GEJ adenocarcinoma who had progressed on ≥2 prior chemotherapy regimens and had ECOG PS 0-1. Pts received pembro 200 mg Q3W up to 2 y or up to disease progression, investigator/pt decision to withdrawal, or unacceptable toxicity. PD-L1+pts had expression in ≥1% tumor or stromal cells using IHC (22C3 antibody). Primary end points: ORR (RECIST 1.1, by central review), safety, and tolerability. Results: Of 259 pts in cohort 1, 76.4% were men; median age was 62.0 y. 51.7% and 48.3% received pembro as 3rd-line (3L) and 4L+ therapy, respectively. 57.1% had PD-L1+ tumors. At data cutoff (Oct 19, 2016), median duration of follow-up was 5.4 mo (range, 0.5 to 18.7). Overall ORR (CR + PR) was 11.2% (95% CI, 7.6-15.7); 1.9% of pts (95% CI, 0.6-4.4) had CR, 9.3% had PR (95% CI, 6.0-13.5), 17% (95% CI, 12.6-22.1) had SD, and 55.6% (95% CI, 49.3-61.7) had PD. Median DOR was 8.1 mo (range, 1.4+ to 15.1+). ORR was 14.9% (95% CI, 9.4-22.1) in 3L pts and 7.2% (95% CI, 3.3-13.2) in 4L+. In PD-L1+ pts, ORR was 15.5% (95% CI, 10.1-22.4) with 2.0% (95% CI, 0.4-5.8) CR and 13.5% (95% CI, 8.5-20.1) PR; in PD-L1– pts, ORR was 5.5% (95% CI, 2.0-11.6), with 1.8% (95% CI, 0.2-6.5) CR and 3.7% (95% CI, 1.0-9.1) PR. In 3L pts with PD-L1+ tumors, ORR was 21.3% (95% CI, 12.7-32.3), with 4.0% (95% CI, 0.8-11.2) CR; in 3L pts with PD-L1– tumors, ORR was 6.9% (95% CI, 1.9-16.7), with 3.4% (95% CI, 0.4-11.9) CR. Grade 3-5 treatment-related AEs (TRAEs) occurred in 43 pts (16.6%). TRAEs led to discontinuation in 2 pts (abnormal LFT, bile duct stenosis) and were fatal in 2 pts (acute kidney injury, pleural effusion). Conclusions: Pembro showed encouraging efficacy and manageable safety after ≥2 prior lines of therapy in pts with advanced G/GEJ cancer in this large phase 2 trial. Survival and additional biomarker data, including MSI status, will be presented. Clinical trial information: NCT02335411.