Search

Simple Summary: The treatment of resectable gastric and gastroesophageal junction adenocarcinomas is enhanced by a strategy of perioperative chemotherapy (CT) when compared with surgery alone. But, there is still a need for new approaches to further improve outcomes in patients treated with perioperative CT. Cetuximab, a human–murine chimeric monoclonal antibody binds with a high affinity to the EGFR binding site, and has shown activity against a variety of tumors, including G/GEJ adenocarcinomas. This study aimed to evaluate the efficacy and safety of perioperative cetuximab combined with 5-fluorouracil and cisplatin for the treatment of gastric and esophageal adenocarcinoma. The results of this phase two study showed safety but lack of efficacy regarding objective tumor response and absence of major toxicity. Purpose: While perioperative chemotherapy provides a survival benefit over surgery alone in gastric and gastroesophageal junction (G/GEJ) adenocarcinomas, the results need to be improved. This study aimed to evaluate the efficacy and safety of perioperative cetuximab combined with 5-fluorouracil and cisplatin. Patients and Methods: Patients received six cycles of cetuximab, cisplatin, and simplified LV5FU2 before and after surgery. The primary objective was a combined evaluation of the tumor objective response (TOR), assessed by computed tomography, and the absence of major toxicities resulting in discontinuation of neoadjuvant chemotherapy (NCT) (45% and 90%, respectively). Results: From 2011 to 2013, 65 patients were enrolled. From 64 patients evaluable for the primary endpoint, 19 (29.7%) had a morphological TOR and 61 (95.3%) did not stop NCT prematurely due to major toxicity. Sixty patients (92.3%) underwent resection. Sixteen patients (/56 available, 28.5%) had histological responses (Mandard tumor regression grade ≤3). After a median follow-up of 44.5 months, median disease-free and overall survival were 24.4 [95% CI: 16.4–39.4] and 40.3 months [95% CI: 27.5–NA], respectively. Conclusion: Adding cetuximab to the NCT regimen in operable G/GEJ adenocarcinomas is safe, but did not show enough efficacy in the present study to meet the primary endpoint (NCT01360086). [ABSTRACT FROM AUTHOR]

To evaluate R0/R1 resection rate in patients with colorectal liver metastases (CLM) treated with aflibercept plus FOLFIRI after failure of a prior oxaliplatin-based regimen in daily clinical practice. This French, multicentre, prospective, observational cohort (NCT05178745) included patients with CLM (alone or predominant; up to 5 lung nodules <2 cm allowed) initiating aflibercept plus FOLFIRI every 2 weeks per physician choice. Primary endpoint was R0/R1 resection rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), radiological and pathological responses, and safety. A total of 137 patients (median age 65 years, RAS/BRAF mutant 57 %/9 %) were enrolled at 22 French sites. CLM (median 4) were synchronous in 82 %, bilobar in 71 % and located in liver only in 54 %. Overall, 17 % of patients had R0/R1 resection (21 % for patients with liver-only disease). A major pathological response per Blazer score was observed in 55 % of resected patients, along with significantly longer OS (median 34.8 vs 9.1 months, p < 0.0001) and PFS (median 11.4 vs 4.9 months, p < 0.0001) compared to non-resected patients. Post-operative complications occurred in 17 % of patients (all Dindo-Clavien grade I-II) and there was no post-operative deaths. Overall, 34 % had grade ≥ 3 adverse events, mainly general health deterioration and diarrhea. Results suggest that aflibercept plus FOLFIRI, after failure of a prior oxaliplatin-based regimen, allows R0/R1 resection of CLM in almost 20 % of patients with a major pathological response in most cases and a median OS prolonged by more than 3-fold versus non-resected patients. • Most patients with metastatic colorectal cancer die because of liver metastases. • Second-line aflibercept plus FOLFIRI allows metastasis resection in 1 in 5 patients. • Pathological response in resected metastases is major in most cases. • Postoperative morbidity is low. • Survival of resected patients is 3-fold higher than non-resected patients. [ABSTRACT FROM AUTHOR]

To determine if commercially available mouthwash with β-cyclodextrin and citrox (bioflavonoids) (CDCM) could decrease the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) salivary viral load. In this randomized controlled trial, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive patients aged 18–85 years with asymptomatic to mild coronavirus disease 2019 (COVID-19) symptoms for <8 days were recruited. A total of 176 eligible patients were randomly assigned (1:1) to CDCM or placebo. Three rinses daily were performed for 7 days. Saliva sampling was performed on day 1 at 09.00 (T1), 13.00 (T2) and 18.00 (T3). On the following 6 days, one sample was taken at 15.00. Quantitative RT-PCR was used to detect SARS-CoV-2. The intention-to-treat analysis demonstrated that, over the course of 1 day, CDCM was significantly more effective than placebo 4 hours after the first dose (p 0.036), with a median percentage (log 10 copies/mL) decrease T1–T2 of –12.58% (IQR –29.55% to –0.16%). The second dose maintained the low median value for the CDCM (3.08 log 10 copies/mL; IQR 0–4.19), compared with placebo (3.31 log 10 copies/mL; IQR 1.18–4.75). At day 7, there was still a greater median percentage (log 10 copies/mL) decrease in salivary viral load over time in the CDCM group (–58.62%; IQR –100% to –34.36%) compared with the placebo group (–50.62%; IQR –100% to –27.66%). These results were confirmed by the per-protocol analysis. This trial supports the relevance of using CDCM on day 1 (4 hours after the initial dose) to reduce the SARS-CoV-2 viral load in saliva. For long-term effect (7 days), CDMC appears to provide a modest benefit compared with placebo in reducing viral load in saliva. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether self-collected pure saliva (SCPS) is comparable to nasopharyngeal (NP) swabs in the quantitative detection of SARS-CoV-2 by RT-PCR in asymptomatic, mild patients with confirmed COVID-19. Thirty-one patients aged from 18 to 85 years were included between 9 June and 11 December 2020. A SCPS sample and a NP sample were taken for each patient. Quantitative PCR was performed to detect SARS-CoV-2 viral load. Results of SCPS vs. NP samples testing were compared. Statistical analyses were performed. Viral load was significantly correlated (r = 0.72). The concordance probability was estimated at 73.3%. In symptomatic adults, SCPS performance was similar to that of NP swabs (Percent Agreement = 74.1%; p = 0.11). Thus, the salivary test based on pure oral saliva samples easily obtained by noninvasive techniques has a fair agreement with the nasopharyngeal one in asymptomatic, mild patients with a confirmed diagnosis of COVID-19. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) and hepatocyte growth factor (HGF)/mesenchymal–epithelial transition (MET) pathways, which promote tumour growth and proliferation, are often deregulated in advanced gastroesophageal adenocarcinomas. We assessed whether adding panitumumab (an EGFR inhibitor) or rilotumumab (a HGF inhibitor) to first-line fluoropyrimidine-based and platinum-based chemotherapy (modified oxaliplatin, leucovorin and fluorouracil [mFOLFOX6]) benefits to patients with advanced gastroesophageal adenocarcinoma. This phase II, open-label, randomised, three-arm study enrolled patients ≥18 years, with advanced gastroesophageal adenocarcinoma, Eastern Cooperative Oncology Group performance status 0–1 and no known HER2 overexpression. Patients were randomly assigned (1:1:1) mFOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h) alone or combined with panitumumab (6 mg/kg) or rilotumumab (10 mg/kg) every 2 weeks until limiting toxicity, patient's refusal or disease progression. The primary end-point was the 4-month progression-free survival (PFS) rate. Secondary end-points included overall survival (OS) and tolerance. The study enrolled 162 patients in 29 French centres. The median follow-up was 23.6 months (interquartile range = 16.4–29.0). The 4-month PFS rate was 71% (95% confidence interval [CI] = 57–82) with chemotherapy alone, 57% (95% CI = 42–71) combined with panitumumab and 61% (95% CI = 47–74) combined with rilotumumab. Median OS was 13.1 months (95% CI = 8.7–16.9) with chemotherapy alone, 8.3 months (95% CI = 6.2–13.2) combined with panitumumab and 11.5 months (95% CI = 7.9–17.1) combined with rilotumumab. Adverse events grade ≥III occurred less frequently with chemotherapy alone (62%) than with panitumumab (83%) and rilotumumab (89%). We found no benefit in adding panitumumab or rilotumumab to mFOLFOX6 first-line chemotherapy to treat advanced gastroesophageal adenocarcinoma patients. European Clinical Trials Database, number 2009-012797-12. • Fluoropyrimidine-platinum doublets are the standard for advanced gastric cancer. • EGFR and HGF/MET pathways are often deregulated in advanced gastric cancer. • Panitumumab and rilotumumab are directed against EGFR and HGF, respectively. • Adding panitumumab to chemotherapy is ineffective in advanced gastric cancer. • Adding rilotumumab to chemotherapy is ineffective in advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Summary Lenalidomide (LEN) has been shown to yield red blood cell (RBC) transfusion independence in about 25% of lower risk myelodysplastic syndromes (MDS) without del(5q), but its efficacy in patients clearly refractory to erythropoiesis-stimulating agents (ESA) is not known. We report on 31 consecutive lower-risk non-del(5q) MDS patients with anaemia refractory to ESA and treated with LEN in a compassionate programme, 20 of whom also received an ESA. An erythroid response was obtained in 15 patients (48%), including 10 of the 27 (37%) previously transfusion-dependent (RBC-TD) patients, who became transfusion-independent (RBC-TI). Nine of the responders relapsed, whereas 6 (40%) were still responding and transfusion-free after 11+-31+ months. Median response duration was 24 months. The erythroid response rate was lower in refractory cytopenia with multilineage dysplasia (27% vs. 60%) and tended to be higher in patients treated with LEN + ESA (55% vs. 36%). Response duration was significantly longer in responders who obtained RBC-TI and in patients treated with LEN after primary resistance to ESA. The main toxicity of LEN was cytopenias. We confirm that, in a patient population of lower risk MDS without del 5q clearly resistant to ESA, LEN is an interesting second line therapeutic option. Its combination with ESAs in this context warrants prospective studies. [ABSTRACT FROM AUTHOR]