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The addition of camrelizumab to gemcitabine and cisplatin showed promising activity as first-line therapy in patients with recurrent or metastatic nasopharyngeal carcinoma in a phase 1 trial. We therefore compared camrelizumab plus gemcitabine and cisplatin with placebo plus gemcitabine and cisplatin in a randomised phase 3 trial. In this randomised, double-blind, phase 3 trial done at 28 hospitals in China, patients were eligible if they were aged 18–75 years, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and had previously untreated recurrent or metastatic nasopharyngeal carcinoma. Patients were randomly assigned (1:1; using an interactive web-response system with a block size of four) to receive either camrelizumab (200 mg on day 1) or matching placebo intravenously, plus gemcitabine and cisplatin (gemcitabine 1000 mg/m2 on days 1 and 8; cisplatin 80 mg/m2 on day 1) intravenously every 3 weeks for four to six cycles, followed by maintenance therapy with camrelizumab or placebo, until radiographic progression, unacceptable toxicity, start of new anticancer treatment, investigator decision, or withdrawal of consent. Stratification factors used in randomisation were liver metastases, previous radical concurrent chemoradiotherapy, and ECOG performance status. The allocation sequence was generated by an independent randomisation group. The primary endpoint was progression-free survival per independent review committee. The significance threshold for independent review committee-assessed progression-free survival was p=0·0086 (one-sided) at the interim analysis. Efficacy and safety analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03707509, and is closed for enrolment but is ongoing. Between Nov 13, 2018, and Nov 29, 2019, 343 patients were screened and 263 were eligible and were randomly assigned to the camrelizumab group (n=134) or placebo group (n=129). At the prespecified interim analysis (June 15, 2020), independent review committee-assessed progression-free survival was significantly longer in the camrelizumab group (median 9·7 months [95% CI 8·3–11·4]) than in the placebo group (median 6·9 months [5·9–7·3]; hazard ratio 0·54 [95% CI 0·39–0·76]; one-sided p=0·0002). As of Dec 31, 2020, the most common grade 3 or worse adverse events of any cause were decreased white blood cell count (89 [66%] of 134 patients in the camrelizumab group vs 90 [70%] of 129 patients in the placebo group), decreased neutrophil count (86 [64%] vs 85 [66%]), anaemia (53 [40%] vs 57 [44%]), and decreased platelet count (53 [40%] vs 52 [40%]). Serious adverse events were reported in 59 (44%) of 134 patients in the camrelizumab group and 48 (37%) of 129 patients in the placebo group. Treatment-related deaths occurred in five (4%) patients in the camrelizumab group (two unknown cause of death, one multiple organ dysfunction syndrome, one pharyngeal haemorrhage, and one arrhythmia) and one (<1%) patient in the placebo group (unknown cause of death). Our findings suggest that camrelizumab plus gemcitabine and cisplatin could be a new standard of care for patients with recurrent or metastatic nasopharyngeal carcinoma in the first-line setting. Longer follow-up is needed to confirm this conclusion. Jiangsu Hengrui Pharmaceuticals (formerly Jiangsu Hengrui Medicine). For the Chinese translation of the abstract see Supplementary Materials section.

Background: Cervical cancer remains the fourth most common malignant cancer in females and the fourth most common cause of mortality in women worldwide. Approximately 70% of new cases are diagnosed as locoregionally advanced cervical cancer (LACC), posing a significant threat to women’s health. Concurrent chemoradiotherapy (CCRT) is the established standard treatment for LACC. However, more than 30% of patients still experience local recurrence and distant metastasis. Improving treatment outcomes for LACC is a critical global objective. Objective: To investigate the safety and efficacy of adding Endostar to CCRT in patients with LACC. Design: This is a multicenter, open-label, randomized, controlled, phase II trial. Methods: A total of 120 patients were randomly allocated (1:1) to receive either CCRT alone (definitive radiotherapy plus cisplatin 40 mg/m2 every week for 4–5 cycles) or CCRT plus Endostar, Endostar at a dose of 7.5 mg/m2/day, from 5 days before CCRT for 10 consecutive days every 15 days for four cycles). Results: The CCRT + E arm demonstrated a significantly higher complete response rate (CRR) compared to the CCRT arm (68.3% vs 35.0%, p = 0.001), while the overall response rate (ORR) was similarly in both arms (98.3% vs 100%, p = 1.000). The CCRT + E arm showed significantly improved distant metastasis-free survival (DMFS) (1-year: 91.6% vs 94.8%, 2-year: 82.3% vs 91.6%, 5-year: 67.0% vs 88.0% p = 0.029). No significant differences were found in overall survival (OS), progression-free survival (PFS), or locoregional recurrence-free survival (LRFS) (p > 0.05). Multivariable analysis identified maximum tumor diameter >4 cm and failure to achieve CR as predictive factors of poor PFS, and maximum tumor diameter >4 cm and stage IIIA–IVA disease as poor prognostic factors for OS. According to the subgroup analysis, Endostar significantly improved the DMFS in cohorts of patients with squamous cell carcinoma (p = 0.005), a maximum tumor diameter > 4 cm (p = 0.011), and stage IB2 or IIA2–IIB disease (p = 0.005). The rates of acute and late adverse reactions were similar in both arms (p > 0.05), with no cardiac toxicity, hypertension, or grade 5 toxicity reported. Conclusion: The addition of Endostar to CCRT significantly enhanced tumor response (CRR) and reduced distant metastasis (DMFS) in LACC patients without increasing treatment toxicity, offering a promising therapeutic enhancement. Clinically, patients with squamous cell carcinoma, maximum tumor diameter > 4 cm, and International Federation of Gynecology and Obstetrics stage IB2 or IIA2–IIB disease derived particularly robust DMFS benefits from the combination regimen, suggesting they should be prioritized for this approach. Although the 5-year DMFS results are encouraging, validation in a larger phase III study and longer follow-up are warranted before considering this regimen as a new standard treatment modality for LACC. Trial registration: This trial was registered at ClinicalTrials.gov (NCT 03086681, registered 22 March 2017, https://clinicaltrials.gov/study/NCT03086681.

Background Nimotuzumab (NTZ) is an anti-EGFR monoclonal antibody. However,the effect of targeted drugs combined with induction therapy in locally advanced nasopharyngeal carcinoma remains unclear. The aim of this study is to investigate the safety and efficacy of NTZ combined with cisplatin plus 5-fluorouracil (PF) as induction regimen in locally advanced nasopharyngeal carcinoma (NPC) patients receiving concurrent radiochemotherapy. Methods This was a multicenter randomized controlled study performed in eight Guangxi hospitals in 2015–2017. Eligible patients with NPC were randomized into nimotuzumab/PF (NPF group) and docetaxel/PF (DPF group) regimens, respectively, as induction therapy. After 2 cycles of induction therapy, all patients received cisplatin and concurrent intensity modulated radiation therapy (IMRT). Then, the two groups were compared for safety and efficacy. Results A total of 118 patients with stage III-IVa NPC were assessed, with 58 and 60 in the NPF and DPF groups, respectively. Compared with DPF treatment, NPF induction therapy showed a more pronounced effect on cervical lymph nodes ( P  = 0.036), with higher response rate (RR) (81% vs 60%). Compared with the DPF group, the NPF group showed significantly reduced leukopenia, neutropenia and gastrointestinal reactions (all P  < 0.05); rash only appeared in the NPF group, but all cases were grade 1. During concurrent treatment with radiotherapy and chemotherapy, the NPF group showed better tolerance to radiotherapy and chemotherapy; neutropenia, anemia, gastrointestinal reactions, oral mucositis and radiation dermatitis in the NPF group were significantly reduced ( P  < 0.05). The expression rate of EGFR was 94.9% (112/118). Compared with the DPF group, patients with EGFR expression in the NPF group showed better response (77.8% vs 63.0%, P  = 0.033). Conclusion For locally advanced NPC patients receiving follow-up cisplatin and IMRT, nimotuzumab/PF for induction therapy has better lymph node response rate and milder adverse reactions than the DPF regimen. In addition, the patients have better tolerance in subsequent concurrent radiotherapy and chemotherapy; however, long-term efficacy needs further follow-up evaluation. Trial registration The registration number of the clinical trial is ChiCTR-OIC-16008201 and retrospectively registered on March 31, 2016.

Tumor-associated macrophages (TAMs) are pivotal for tumor progression and metastasis. We investigated the stromal CD86+TAM/CD163+TAM (CD86/CD163) ratio as a novel prognostic biomarker for stage II-III colorectal cancer (CRC). Two independently clinical cohorts of stage II-III CRC were retrospectively enrolled in this study. TAMs were detected using immunohistochemical staining for CD86 and CD163. The stromal CD86/CD163 ratio was calculated as a prognostic biomarker for recurrence-free survival (RFS) and overall survival (OS). Patients with a low CD86/CD163 ratio had shorter RFS (HR=0.193, p <0.001) and OS (HR=0.180, p <0.001) than patients with a high CD86/CD163 ratio in the training cohort. CD86/CD163 ratio may be an independent predictor for RFS (HR=0.233, p <0.001) and OS (HR=0.224, p <0.001) in the training cohort. We obtained equivalent results in the validation cohort. The CD86/CD163 ratio tends to have better predictive values than tumor stage in the training (AUC: 0.682 vs 0.654, p =0.538) and validation (AUC: 0.697 vs 0.659, p =0.586) cohorts. CD86/CD163 ratio effectively predicts RFS for stage II (HR=0.203, p <0.001) and stage III CRC (HR=0.302, p <0.001). CD86/CD163 ratio also effectively predicts RFS in CRC patients with adjutant chemotherapy (HR=0.258, p <0.001) and without adjutant chemotherapy (HR=0.205, p <0.001). The stromal CD86/CD163 ratio could be used for individual risk assessment of recurrence and mortality for stage II-III CRC. Together with tumor stage, this ratio will aid in the personal treatment.

Flavonoids are naturally occurring compounds with diverse health-promoting properties. The purpose of this study was to explore the associations between dietary flavonoid intake and cardiovascular health in cancer survivors. We obtained data from the National Health and Nutrition Examination Survey (NHANES) 2007-2008, 2009-2010, and 2017-2018 cycles. Weighted linear regression and restricted cubic spline (RCS) were used to explore the correlation between dietary flavonoid intake and cardiovascular health (Life's Essential 8 (LE8) score) in cancer survivors. Then, weighted quantile sum (WQS) regression and quantile-based g-computation (qgcomp) models were performed to assess the mixed effects of the six flavonoid subclasses and to determine the major flavonoid types. Additionally, the protective effect of high flavonoid intake on cardiovascular health was further evaluated in different subgroups, and mediation analysis was used to explore mediating factors. After adjusting for all covariates, compared to those in the first quartile, participants in the fourth quartile of total flavonoids, anthocyanidins, flavonols, flavanones, and flavones intake exhibited increases in LE8 scores of 3.24% (95% CI: 0.45-6.03, for trend=0.030), 6.25% (95% CI: 3.14-9.36, for trend<0.001), 3.01% (95% CI: 1.33-4.69, for trend= 0.003), 3.23% (95% CI: 0.18-6.27, for trend=0.030), and 5.01% (95% CI: 2.42-7.61, for trend<0.001), respectively. Meanwhile, significant non-linear relationships were supported by the RCS models. However, the weighted linear regression and RCS models did not reveal any clear correlations between isoflavone or flavan-3-ol intake and the LE8 score. Regarding mixed effects, anthocyanidin, flavonol, flavanone, and flavone intake were positively related to the LE8 score according to both the WQS and qgcomp models, and anthocyanidin intake was the major contributor. Our study indicated that dietary flavonoid intake is positively associated with cardiovascular health in cancer survivors, among which anthocyanidin intake might provide the most benefit.