Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial.

Gastric and gastroesophageal junction (G/GEJ) cancers carry a poor prognosis, and despite recent advancements, most patients die of their disease. Although immune checkpoint blockade became part of the standard-of-care for patients with metastatic G/GEJ cancers, its efficacy and impact on the tumor microenvironment (TME) in early disease remain largely unknown. We hypothesized higher efficacy of neoadjuvant immunotherapy plus chemotherapy in patients with nonmetastatic G/GEJ cancer. In the phase 2 PANDA trial, patients with previously untreated resectable G/GEJ tumors (n = 21) received neoadjuvant treatment with one cycle of atezolizumab monotherapy followed by four cycles of atezolizumab plus docetaxel, oxaliplatin and capecitabine. Treatment was well tolerated. There were grade 3 immune-related adverse events in two of 20 patients (10%) but no grade 4 or 5 immune-related adverse events, and all patients underwent resection without treatment-related delays, meeting the primary endpoint of safety and feasibility. Tissue was obtained at multiple time points, allowing analysis of the effects of single-agent anti-programmed cell death ligand 1 (PD-L1) and the subsequent combination with chemotherapy on the TME. Twenty of 21 patients underwent surgery and were evaluable for secondary pathologic response and survival endpoints, and 19 were evaluable for exploratory translational analyses. A major pathologic response (≤10% residual viable tumor) was observed in 14 of 20 (70%, 95% confidence interval 46-88%) patients, including 9 (45%, 95% confidence interval 23-68%) pathologic complete responses. At a median follow-up of 47 months, 13 of 14 responders were alive and disease-free, and five of six nonresponders had died as a result of recurrence. Notably, baseline anti-programmed cell death protein 1 (PD-1)+CD8+ T cell infiltration was significantly higher in responders versus nonresponders, and comparison of TME alterations following anti-PD-L1 monotherapy versus the subsequent combination with chemotherapy showed an increased immune activation on single-agent PD-1/L1 axis blockade. On the basis of these data, monotherapy anti-PD-L1 before its combination with chemotherapy warrants further exploration and validation in a larger cohort of patients with nonmetastatic G/GEJ cancer. ClinicalTrials.gov registration: NCT03448835 .

Cardiovascular risk factors and specific coronary artery calcification in postmenopausal women

Myocardial infractions at different locations have been related to different sets of risk factors. This study was designed to examine the association between cardiovascular risk factors and specific coronary artery calcification [CAC]. The study population comprised 573 postmenopausal women selected from a population-based cohort study. Established vascular risk factors were measured. The women underwent a multi detector-row computed tomography [16-MDCT] [Philips Mx 8000 IDT 16] to assess coronary calcium. The Agatston score was used to quantify coronary calcium. Logistic regression models were utilized to assess the relations. The prevalence of coronary artery calcification [Agatston score >0] was 61.5% [n= 348]. CAC was most common in the left anterior descending [LAD] artery with a prevalence of 43.9%; and the rates of prevalence in the right coronary arter [RCA], the circumflex [LCX], the left main artery [LM], and the posterior descending artery [PDA] were 23.1%, 19.4%, 15.8%, and 0.3%, respectively. In the multivariate regression models, age was predominantly related to the calcification in the LAD and LCX, low density lipoprotein to calcification in the LAD, and cholesterol to the calcification of the RCA. Hypertension and systolic and diastolic blood pressure were related to the calcification of the LCX, whereas smoking was predominantly related to the calcification of both LAD and RCA. Finally, age, body mass index, and systolic blood pressure were significantly related to teh classification in the LM. Our findings showed that the consequences of elevated risk factor levels on the development of atherosclerosis appeared to be different across the segments of the coronary arteries