Willingness to receive the second booster of COVID-19 vaccine among older adults with cancer: a stratified analysis in four provinces of China.

Background: Despite the elevated COVID-19 risk for older adults with cancer, vaccine hesitancy poses a significant barrier to their immunization. Intriguingly, there is limited research on the prevalence of willingness to receive the second booster dose and associated determinants in older adults with cancer. Objective: Our objective was to ascertain the level of awareness about COVID-19 vaccines and to uncover the factors influencing the willingness to receive the second booster among Chinese cancer patients aged 65 years and over. Methods: To achieve our objective, we conducted a multicenter cross-sectional study in four tertiary hospitals from four provinces of China. This involved using a Health Belief Model (HBM) based self-administered questionnaire and medical records. Subsequently, we employed multivariable logistic regression to identify factors influencing the second COVID-19 booster vaccine willingness. Results: Our results showed that among 893 eligible participants, 279 (31.24%) were aged 65 years and over, and 614 (68.76%) were younger. Interestingly, the willingness to receive the second COVID-19 booster vaccine was 34.1% (95/279) (OR: 1.043, 95% CI: 0.858, 1.267) in participants aged 65 years and over, which was similar to participants aged under 65 years (34.1% vs. 35.5%, p = 0.673). Furthermore, our findings revealed that a positive attitude toward the booster and recommendations from healthcare providers and family members were positively associated with vaccine willingness. Conversely, perceptions of negative impacts on cancer control and vaccine accessibility regarding the second COVID-19 booster were inversely related to the outcome event (all p < 0.05). Conclusion: Our study concludes with the finding of a low willingness toward the second COVID-19 booster in Chinese cancer patients, particularly in the older adults, a fact which warrants attention. This reluctance raises their risk of infection and potential for severe outcomes. Consequently, we recommend using media and community outreach to dispel misconceptions, promote the booster's benefits, and encourage vaccine discussions with healthcare providers and family members.

Dual CTLA-4 and PD-1 checkpoint blockade using CS1002 and CS1003 (nofazinlimab) in patients with advanced solid tumors: A first-in-human, dose-escalation, and dose-expansion study.

BACKGROUND: This study investigated the safety and efficacy of an anti-CTLA-4 monoclonal antibody (CS1002) as monotherapy and in combination with an anti-PD-1 monoclonal antibody (CS1003) in patients with advanced/metastatic solid tumors. METHODS: The phase 1 study involved phase 1a monotherapy dose-escalation (part 1) and phase 1b combination therapy dose escalation (part 2) and expansion (part 3). Various dosing schedules of CS1002 (0.3, 1, or 3 mg/kg every 3 weeks, or 3 mg/kg every 9 weeks) were evaluated with 200 mg CS1003 every 3 weeks in part 3. RESULTS: Parts 1, 2, and 3 included a total of 13, 18, and 61 patients, respectively. No dose-limiting toxicities or maximum tolerated doses were observed. Treatment-related adverse events (TRAEs) were reported in 30.8%, 83.3%, and 75.0% of patients in parts 1, 2, and 3, respectively. Grade ≥3 TRAEs were experienced by 15.4%, 50.0%, and 18.3% of patients in each part. Of 61 patients evaluable for efficacy, 23 (37.7%) achieved objective responses in multiple tumor types. Higher objective response rates were observed with conventional and high-dose CS1002 regimens (1 mg/kg every 3 weeks or 3 mg/kg every 9 weeks) compared to low-dose CS1002 (0.3 mg/kg every 3 weeks) in microsatellite instability-high/mismatch repair-deficient tumors, melanoma, and hepatocellular carcinoma (50.0% vs. 58.8%, 14.3% vs. 42.9%, and 0% vs. 16.7%). CONCLUSION: CS1002, as monotherapy, and in combination with CS1003, had a manageable safety profile across a broad dosing range. Promising antitumor activities were observed in patients with immune oncology (IO)-naive and IO-refractory tumors across CS1002 dose levels when combined with CS1003, supporting further evaluation of this treatment combination for solid tumors. PLAIN LANGUAGE SUMMARY: CS1002 is a human immunoglobulin (Ig) G1 monoclonal antibody that blocks the interaction of CTLA-4 with its ligands and increases T-cell activation/proliferation. CS1003, now named nofazinlimab, is a humanized, recombinant IgG4 monoclonal antibody that blocks the interaction between human PD-1 and its ligands. In this original article, we determined the safety profile of CS1002 as monotherapy and in combination with CS1003. Furthermore, we explored the antitumor activity of the combination in anti-programmed cell death protein (ligand)-1 (PD-[L]1)-naive microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) pan tumors, and anti-PD-(L)1-refractory melanoma and hepatocellular carcinoma (HCC). CS1002 in combination with CS1003 had manageable safety profile across a broad dosing range and showed promising antitumor activities across CS1002 dose levels when combined with CS1003. This supports further assessment of CS1002 in combination with CS1003 for the treatment of solid tumors.

Low uptake of COVID-19 booster doses among elderly cancer patients in China: A multicentre cross-sectional study.

Background: Vaccination is a crucial measure to control the spread of coronavirus disease 2019 (COVID-19) pandemic. The elderly and cancer populations both are more susceptible to SARS-CoV-2 and have higher mortality. However, the uptake of COVID-19 vaccine booster doses among elderly cancer patients remains unclear. This study aimed to investigate the prevalence and associates of COVID-19 vaccine booster doses uptake in elderly cancer patients. Methods: A multi-center cross-sectional survey was conducted in four general populations of China province from April to June 2022. Demographic and clinical characteristics, as well as COVID-19 vaccination status and reasons for not uptake booster doses, were collected through face-to-face interviews and medical records. Multivariable logistic regression models were performed to explore the associates of the first COVID-19 booster dose vaccination uptake of cancer patients. Results: A total of 893 cancer patients were eventually included in this study, of which 279 (31.24%) were aged 65 or older and 614 (68.76%) were under 65 years old. The proportion of the first COVID-19 vaccine booster dose among cancer patients aged 65 and above was lower than among adults aged 65 (23.66 vs. 31.92%). Factors affecting individual-level variables among the aged 65 and above cancer patients group whether to uptake the first COVID-19 booster dose were negative attitudes toward COVID-19 vaccine booster dose, perceived subjective norm, perceived behavioural control, and other types of chronic disease. There is no significant difference in the incidence of related adverse reactions between the two age groups (P = 0.19). Conclusions: Low uptake of COVID-19 vaccine booster doses among elderly cancer patients is a significant concern and implies high susceptibility and high fatality when facing the emergence of SARS Cov-2 outbreak. Efforts to improve vaccine education and accessibility, particularly in rural areas, may help increase uptake and reduce the spread of SARS-Cov-2.

A first-in-human phase 1 study of nofazinlimab, an anti-PD-1 antibody, in advanced solid tumors and in combination with regorafenib in metastatic colorectal cancer.

BACKGROUND: We assessed nofazinlimab, an anti-PD-1 antibody, in solid tumors and combined with regorafenib in metastatic colorectal cancer (mCRC). METHODS: This phase 1 study comprised nofazinlimab dose escalation (phase 1a) and expansion (phase 1b), and regorafenib dose escalation (80 or 120 mg QD, days 1-21 of 28-day cycles) combined with 300-mg nofazinlimab Q4W (part 2a) to determine safety, efficacy, and RP2D. RESULTS: In phase 1a (N = 21), no dose-limiting toxicity occurred from 1 to 10 mg/kg Q3W, with 200 mg Q3W determined as the monotherapy RP2D. In phase 1b (N = 87), 400-mg Q6W and 200-mg Q3W regimens were found comparable. In part 2a (N = 14), both regimens were deemed plausible RP2Ds. Fatigue was the most frequent treatment-emergent adverse event (AE) in this study. Any-grade and grade 3/4 nofazinlimab-related AEs were 71.4% and 14.3%, 56.3% and 5.7%, and 57.1% and 21.4% in phases 1a, 1b, and part 2a, respectively. ORRs were 14.3% and 25.3% in phases 1a and 1b, respectively. In part 2a, no patients had radiological responses. CONCLUSIONS: Nofazinlimab monotherapy was well tolerated and demonstrated preliminary anti-tumor activity in multiple tumor types. Regorafenib plus nofazinlimab had a manageable safety profile but was not associated with any response in mCRC. CLINICAL TRIAL REGISTR ATION: Clinicaltrials.gov (NCT03475251).

Concerns related to the interactions between COVID-19 vaccination and cancer/cancer treatment were barriers to complete primary vaccination series among Chinese cancer patients: A multicentre cross-sectional survey.

COVID-19 vaccination is effective for cancer patients without safety concerns. However, COVID-19 vaccination hesitancy is common among cancer patients. This study investigated factors affecting primary COVID-19 vaccination series completion rate among cancer patients in China. A multicentre cross-sectional study was conducted in four Chinese cities in different geographic regions between May and June 2022. A total of 893 cancer inpatients provided written informed consent and completed the study. Logistic regression models were fitted. Among the participants, 58.8% completed the primary COVID-19 vaccination series. After adjusting for background characteristics, concerns about interactions between COVID-19 vaccination and cancers/cancer treatment (adjusted odds ratios [AOR]: 0.97, 95%CI: 0.94, 0.99) were associated with lower completion of primary vaccination series. In addition, perceived higher risk of COVID-19 infection comparing to people without cancers (AOR: 0.46, 95%CI: 0.24, 0.88), perceived a high chance of having severe consequences of COVID-19 infection (AOR: 0.68, 95%CI: 0.51, 0.91) were also associated with lower completion rate. Being suggested by significant others (AOR: 1.32, 95%CI: 1.23, 1.41) and perceived higher self-efficacy to receive COVID-19 vaccination (AOR: 1.48, 95%CI: 1.31, 1.67) were positively associated with the dependent variable. Completion rate of primary COVID-19 vaccination series was low among Chinese cancer patients. Given the large population size and their vulnerability, this group urgently needs to increase COVID-19 vaccination coverage. Removing concerns about interactions between COVID-19 vaccination and cancers, using fear appeal approach, involving significant others, and facilitating patients to make a plan to receive COVID-19 vaccination might be useful strategies.

Hesitancy to Receive the Booster Doses of COVID-19 Vaccine Among Cancer Patients in China: A Multicenter Cross-Sectional Survey - Four PLADs, China, 2022.

What is already known about this topic?: Cancer patients are more vulnerable and have higher mortality rates from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population; however, coverage for booster doses of the coronavirus disease 2019 (COVID-19) vaccine was low among cancer patients in China. What is added by this report?: Overall, 32.0% and 56.4% of cancer patients from four Provincial Level Administrative Divisions (PLADs) expressed hesitancy toward the first and second booster doses, respectively. Factors negatively associated with hesitancy to receive booster doses included positive attitudes, perceived support, and higher exposure to COVID-19 vaccination information. Conversely, postvaccination fatigue was positively associated with vaccine hesitancy. What are the implications for public health practice?: Improved COVID-19 vaccination coverage is needed to promote health for cancer patients.

Cyr61 overexpression induced by interleukin 8 via NF-kB signaling pathway and its role in tumorigenesis of gastric carcinoma in vitro.

Cyr61 (CCN1) is a multifunctional matricellular protein in bridging inflammation and cancer, involved in many biological functions such as tumorigenesis and carcinogenesis. The role of Cyr61 in gastric cancer (GC) has not been fully understood and needs to be investigated and clarified. We examined Cyr61 expression in 6 GC cell lines and stable transfection of recombinants in to BGC823 specifically down regulated the Cyr61 mRNA and protein expression shown by the analysis with western blot, RT-PCR, western blot and immunofluorescence assay. The cells treated with siRNA shown markedly reduced activity in growth, migration and invasion compared with parental BGC823 cells as well as mock transfectants. The Cyr61 deficient cells demonstrated significantly inhibited colony formation in soft agar and reduced tumorigenicity was showed in nude mice, NF-kB pathway evidently inactivated respectively. However, under the stimulation of IL-8, the siRNA-treated cells can restore the capacity of proliferation and invasion. IL-8 can induce the high expression of Cyr61 and MMP11 through NF-kB signal pathway. Silencing of Cyr61 can inhibit or minimize the proliferation and invasiveness of gastric cancer cell. The results imply that Cyr61 enhance the proliferation and invasion of gastric cancer cells and this process is partially modulated by the IL-8 up-regulation. Cyr61 may mediate the proliferation and development of gastric carcinoma.