Assessment of Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients with advanced HER-2 negative gastric or gastroesophageal junction cancers: the ARMANI phase III trial

Background: Platinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4\u20136 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment. Methods: This is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis. (Continued on next page) Discussion: The ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression. Trial registration: ARMANI is registered at ClinicalTrials.gov (NCT02934464, October 17, 2016) and EudraCT(2016\u2013001783-12, April 202,016)

Computed tomography-derived myocardial extracellular volume: an early biomarker of cardiotoxicity in esophageal cancer patients undergoing radiation therapy

Objectives: We aimed to assess extracellular volume (ECV) through non-gated, contrast-enhanced computed tomography (CT) before and after radiation therapy (RT) in patients with esophageal cancer (EC). Materials and methods: EC patients who had undergone CT before and after RT were retrospectively assessed. Patients with preexisting cardiovascular disease or with heavily artifacted CT were excluded. ECV was calculated using density values for the myocardial septum and blood pool. Data were reported as mean and standard deviation or median and interquartile range according to their distribution; t test or Wilcoxon and Pearson r or Spearman \u3c1 were subsequently used. Results: Twenty-one patients with stage 65 IB EC, aged 64 \ub1 18 years, were included. Mean and maximum RT doses were 21.2 Gy (16.9\u201324.1) and 42.5 Gy (41.8\u201349.2), respectively. At baseline (n = 21), hematocrit was 39% \ub1 4%, ECV 27.9% \ub1 3.5%; 35 days (30\u201338) after RT (n = 20), hematocrit was 36% \ub1 4%, lower than at baseline (p = 0.002), ECV 30.3% \ub1 8.3%, higher than at baseline (p = 0.081); at follow-up 420 days (244\u2013624) after RT (n = 13), hematocrit was 36% \ub1 5%, lower than at baseline (p = 0.030), ECV 31.4% \ub1 4.5%, higher than at baseline (p = 0.011). No patients showed signs of overt cardiotoxicity. ECV early after RT was moderately positively correlated with maximum RT dose (\u3c1 = 0.50, p = 0.036). Conclusions: In EC patients, CT-derived myocardial ECV was increased after RT and may thus appear as a potential early biomarker of cardiotoxicity