A Randomized Phase II Study of Perioperative Chemotherapy Plus Bevacizumab Versus Postoperative Chemotherapy Plus Bevacizumab in Patients With Upfront Resectable Hepatic Colorectal Metastases

IntroductionWhether patients with resectable colorectal liver metastases (CRLM) gain a survival benefit from perioperative chemotherapy remains controversial. The benefit of including bevacizumab in chemotherapy also remains unclear.Material and MethodsSeventy-six patients with CRLM were randomly assigned to either 6 cycles of FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin)/FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) with bevacizumab before and after surgery or 12 cycles after surgery. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and compared by the log-rank test.ResultsThe median PFS of all patients was 37.4 months at 5.4 years follow-up, and the median overall survival (OS) was not reached. The PFS between the perioperative group and the postoperative group did not reveal a statistical difference (P = .280). The OS was significantly better in the perioperative group (hazard ratio [HR], 0.60; 95% confidence interval [CI],) 0.35-1.02; P = .049). In subgroup patients with carcinoembryonic antigens (CEA) ≥ 5 ng/mL or those with over 2 liver metastases, perioperative group had longer OS than postoperative group (CEA: HR, 0.49; 95% CI, 0.25-0.93; P = .030; number of liver metastases: HR, 0.55; 95% CI, 0.30-0.99; P = .049). The largest liver metastases size, disease-free interval, and sidedness did not affect PFS or OS. There was no difference between the 2 groups in postoperative complications with bevacizumab or adverse events during chemotherapy.ConclusionsIn patients with resectable CRLMs, perioperative chemotherapy had no effect on PFS, but improved OS. Patients with high CEA levels or over 2 liver metastases may benefit from perioperative chemotherapy.     

IMpower150 Final Overall Survival Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in First-Line Metastatic Nonsquamous NSCLC

IntroductionWe report the final overall survival (OS) analyses of atezolizumab-carboplatin-paclitaxel (ACP [experimental arm]) and OS data with approximately 39.8 months of median follow-up with atezolizumab-bevacizumab-carboplatin-paclitaxel (ABCP) versus bevacizumab-carboplatin-paclitaxel (BCP) in chemotherapy-naive patients with metastatic nonsquamous NSCLC in the phase 3 IMpower150 study (NCT02366143).MethodsIn this randomized, open-label study (N = 1202), coprimary end points included investigator-assessed progression-free survival and OS in intention-to-treat (ITT) wild-type (WT; no EGFR or ALK alterations) patients. Secondary and exploratory end points included OS in ITT and programmed death-ligand 1 (PD-L1) subgroups defined by the VENTANA SP142 and SP263 immunohistochemistry assays.ResultsAt the final analysis with ACP versus BCP (data cutoff: September 13, 2019; minimum follow-up: 32.4 mo), ACP had numerical, but not statistically significant, improvements in OS (ITT-WT: median OS = 19.0 versus 14.7 mo; hazard ratio = 0.84; 95% confidence interval: 0.71–1.00). OS benefit was sustained with ABCP versus BCP (ITT-WT: 19.5 versus 14.7 mo; hazard ratio = 0.80; 95% confidence interval: 0.67–0.95). Exploratory analyses in the SP142-defined PD-L1 subgroups revealed longer median OS with ABCP and ACP versus BCP in PD-L1–high and PD-L1–positive subgroups; in the PD-L1–negative subgroups, median OS was similar with ACP and ABCP versus BCP. Safety was consistent with that in earlier analyses (data cutoff: January 22, 2018).ConclusionsAt the final IMpower150 OS analysis, ACP had numerical, but not statistically significant, OS improvement versus BCP. Updated data with an additional 20 months of follow-up revealed continued OS improvement with ABCP versus BCP in all patients.     

Systemic effects after intravitreal injection of bevacizumab in new born rabbit eyes

Purpose: To determine the systemic impact of intravitreal injection of bevacizumab (IVB), an anti-vascular endothelium growth factor antibody, in newborn rabbits.

Materials and methods: We used four groups of rabbits. Group 1 rabbits received a single injection of IVB starting from the age of 6?weeks. Group 2 rabbits received a single injection of balanced salt solution (BSS, 0.025?ml) and served as controls for group 1. Group 3 rabbits received two consecutive injections of IVB at the ages of 6 and 10?weeks. Group 4 rabbits received two consecutive injections of BSS at the ages of 6 and 10?weeks and served as controls for group 3. During the experiment, a complete blood count (CBC), clinical biochemistry, weight gain, food intake, body temperature, blood pressure, pulse, and mortality were measured in the animals. Two months after IVB injection, the animals were sacrificed, and histology of the major organs was checked. Immunohistochemistry was assessed to explore the neurons in the central nervous system (CNS).

Results: We found there were no morphological or functional changes in the eyes following IVB injection. Furthermore, there were no differences in CBC, biochemistry, or other measured parameters among the four groups of animals. We checked the histology of the major organs and neurons in the CNS and they did not reveal significant differences among the four groups of animals.

Conclusions: Conclusively, IVB of either one or two injections (0.625?mg) in newborn rabbit eyes is well tolerated and does not cause noticeable systemic organ pathology.     

贝伐珠单抗综合治疗Ⅲ期非小细胞肺癌患者的疗效及其对VEGF、MMP-9及COX-2表达的影响

目的 探讨贝伐珠单抗综合治疗Ⅲ期非小细胞肺癌（NSCLC）患者的疗效及其对患者血管内皮生长因子（VEGF）、基质金属蛋白酶-9（MMP-9）及环氧化酶-2（COX-2）表达的影响。方法 回顾性分析安徽省第二人民医院2017年1月至2019年12月收治的95例Ⅲ期NSCLC患者临床资料,并按照治疗方案不同分为联合组47例、化疗组48例。化疗组实施常规化疗,联合组则于常规化疗的基础上增用贝伐珠单抗治疗。比较两组临床疗效,治疗前后血清VEGF、MMP-9及COX-2水平及毒副反应（包括胃肠道反应、神经毒性、血液毒性、手足综合征以及高血压等）差异。结果 联合组症状缓解的总体有效率为85.11%,高于化疗组的62.50%,差异有统计学意义（χ²=6.259,P=0.012）。联合组血清VEGF、MMP-9及COX-2水平治疗前后差值均高于化疗组,差异均有统计学意义（t=121.293、55.989、23.538;P均<0.05）。两组胃肠道反应、神经毒性、血液毒性、手足综合征以及高血压发生率比较,差异均无统计学意义（P均>0.05）。结论 贝伐珠单抗综合治疗Ⅲ期NSCLC患者疗效尚可,且能有效下调VEGF、MMP-9及COX-2水平,安全性较好,值得临床推广应用。     

Punctate Inner Choroidopathy and Choroidal Neovascularization in Korean Patients

ABSTRACT

Purpose: To describe the clinical features and outcomes of punctate inner choroidopathy (PIC) in Korean patients

Methods: We retrospectively reviewed the medical records of patients with PIC between 2004 and 2015. The main outcome measures included best-corrected visual acuity (BCVA), presence of choroidal neovascularization (CNV), and optical coherence tomography findings. Patients with and without CNV were compared.

Results: Forty eyes of 26 patients were included. The final BCVA was better than 20/40 in 33 eyes (82.5%). CNV was initially present in 12 eyes (30.0%). The mean initial and final logMAR BCVA was poorer for eyes with CNV than for eyes without CNV. Eyes with CNV exhibited a larger myopic refractive error, inflammatory lesions confined within the posterior pole, and a decreased final subfoveal choroidal thickness compared with eyes without CNV.

Conclusion: PIC in the Korean population generally exhibits favorable visual outcomes, and eyes with CNV show more abnormalities and poorer outcomes.