Safety Following COVID-19 Booster Vaccine with BNT162b2 Compared to mRNA-1273 in Solid Cancer Patients Previously Vaccinated with ChAdOx1 or CoronaVac.

Safety data following the COVID-19 booster mRNA vaccine in solid cancer patients are scarce. We prospectively evaluated adverse events after a booster dose of the BNT162b2 vaccine as compared to the mRNA-1273 vaccine in solid malignancy patients who had previously received two doses of ChAdOx1 or heterogenous CoronaVac/ChAdOx1. Data regarding solicited and unsolicited adverse events were collected using questionnaires. The primary endpoint was the difference in incidence and severity of adverse events between BNT162b2 and mRNA-1273 vaccines. A total of 370 subjects were enrolled, including 172 (47%) and 198 (54%) patients receiving booster doses of BNT162b2 and mRNA-1273 vaccines, respectively. The overall incidence of adverse events in the two groups was comparable (BNT162b2 vs. mRNA-1273; 63% vs. 66%, p = 0.6). There was no significant difference in severity, and the majority of adverse events reported were classed as mild to moderate. Tenderness at the injection site was the only reaction that had a statistically higher reported incidence after the mRNA-1273 vaccine than after the BNT162b2 vaccine (56% vs. 41%, p = 0.003). In conclusion, a booster dose of the mRNA vaccine, either BNT162b2 or mRNA-1273, in solid cancer patients previously vaccinated with ChAdOx1 and CoronaVac appears safe, and no new safety concerns were observed.

Safety and Immunogenicity of Homologous and Heterologous Adenoviral-Vectored and mRNA COVID-19 Vaccine Regimens in Radiotherapy Patients.

Diminished immune response after vaccination occurs in cancer patients. This observational study evaluated the immune response and safety profile after COVID-19 vaccination in radiotherapy patients. The study comprised 53 cancer patients undergoing radiotherapy and voluntarily received the COVID-19 vaccine. The two regimens were homologous ChAdOx1-S recombinant (AstraZeneca, AZ), "AZ-AZ" and heterologous "AZ-mRNA". The seroconversion rate and anti-RBD immunoglobulin geometric mean titers (GMT) were assessed and compared with healthy controls. Adverse effects were assessed using a questionnaire. The seroconversion rate was 52.4% 1 month after the first dose with GMT 4.3 U/mL (95%CI 1.4-13). Following the second dose, the AZ-AZ group achieved 95% seroconversion rate with GMT = 188.4 U/mL (95%CI 67.1-529), which was significantly lower than the healthy cohort, GMT = 945 U/mL (95%CI 708-1261). Cancer patients in AZ-mRNA group achieved a 100% seroconversion rate with a high GMT = 1400.8 U/mL (95%CI 429.5-4566), which was significantly lower than the healthy cohort, GMT = 5169.9 U/mL (95%CI 3582.2-7461.5). Most adverse effects were mild. Our findings suggest that radiotherapy patients had fair immunogenicity after the first dose, but achieved a high seroconversion rate after the second dose with manageable adverse effects. However, their immunologic response was lower than in healthy individuals, indicating that other preventive strategies are needed.

Modified albumin-bilirubin predicted survival of unresectable hepatocellular carcinoma patients treated with immunotherapy.

BACKGROUND: Modified albumin-bilirubin (mALBI) grade has been established as a survival determinant in hepatocellular carcinoma (HCC) patients who receive locoregional and targeted therapies. AIM: To investigate whether mALBI could predict survival in unresectable HCC (uHCC) patients who were treated with atezolizumab plus bevacizumab (AB). METHODS: A single-center, retrospective cohort study enrolled uHCC patients who received AB treatment between September 2020 and April 2023 and were followed up until June 2023. An association between mALBI and patient survival was determined using Cox proportional hazards analysis. RESULTS: Of the 83 patients, 67 patients (80.7%) were male with the mean age of 60.6 years. Among them, 22 patients (26.5%) were classified as Barcelona Clinic Liver Cancer B, and 61 patients (73.5%) were classified as Barcelona Clinic Liver Cancer C. Cirrhosis was present in 76 patients (91.6%), with 58 patients classified as Child-Turcotte-Pugh (CTP) A and 18 as CTP B. The median overall survival (OS) and progression-free survival were 13.0 mo [95% confidence interval (CI): 5.2-20.8] and 9.0 mo (95%CI: 5.0-13.0), respectively. The patients were divided into two groups based on mALBI grades: 42 patients (50.6%) in the mALBI 1 + 2a group; and 41 patients (49.4%) in the mALBI 2b + 3 group. During the median follow-up period of 7.0 mo, the mALBI 1 + 2a group exhibited significantly better survival compared to the mALBI 2b + 3 group, with a median OS that was not reached vs 3.0 mo (95%CI: 0.1-6.0, P < 0.001). In a subgroup of patients with CTP A, the mALBI 1 + 2a group also showed significantly longer survival compared to the mALBI 2b + 3 group, with a median OS that was not reached vs 6.0 mo (95%CI: 3.4-8.6, P < 0.001). In the multivariate analysis, both CTP class and mALBI grade were independently associated with survival, with adjusted hazard ratios (95%CI) of 2.63 (1.19-5.78, P = 0.020) and 3.90 (1.71-8.90, P = 0.001), respectively. CONCLUSION: mALBI grades can determine survival of uHCC patients receiving AB treatment, particularly those who have mildly impaired liver function. This highlights the importance of assessing mALBI before initiating AB treatment to optimize therapeutic efficacy in clinical practice.

Effect of Primary Tumor Location on Second- or Later-Line Treatment With Anti-Epidermal Growth Factor Receptor Antibodies in Patients With Metastatic Colorectal Cancer: A Retrospective Multi-Center Study.

BACKGROUND: Current guidelines recommend anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR Ab) as first-line treatment only in patients with left-sided RAS wild type (RASwt) metastatic colorectal cancer (mCRC). However, there are no guideline recommendations specific to tumor sidedness in subsequent-line treatment. This study aimed to investigate the effect of primary tumor location on second- or later-line treatment outcomes in patients with KRASwt mCRC. METHODS: Medical records of patients diagnosed with mCRC at 3 academic centers in Thailand (Siriraj, Chulalongkorn, and Ramathibodi hospital) between 2008 and 2019 were retrospectively reviewed. Patients with KRASwt mCRC who received anti-EGFR Ab in second- or later-line treatment were included. The impact of tumor sidedness on progression-free survival (PFS) was determined using Kaplan-Meier method, and those results were compared using log-rank test. RESULTS: Among the 2,102 patients who had KRAS analysis data, 1,130 (54%) patients had KRASwt. Of those, 413 patients received anti-EGFR Ab in second- or later-line treatment. One hundred and sixty-two of 413 (39%) patients had extended RAS analysis. Seventy (17%) patients had right-sided tumors. Two hundred and thirty-eight (58%) patients received anti-EGFR Ab in the third line, and 132 (32%) patients and 43 (10%) patients were treated in the second and more than third line, respectively. Single-agent irinotecan was the most commonly used backbone chemotherapy (303/413, 73%). Patients with right-sided tumors had non-significantly inferior PFS compared to patients with left-sided tumors (median PFS: 5.7 months (mo), 95% confidence interval [CI]: 3.9-7.5 vs. 7.5 mo, 95% CI 6.5-8.5; p=0.17). Subgroup analysis showed no difference in PFS when stratified by treatment lines. Patient with right-sided tumors had significantly inferior OS compared to patients with left-sided tumors (median OS: 23.3 mo vs. 29.9 mo; p=0.005). CONCLUSIONS: To date, this is the largest real world data of the effect of primary tumor location on anti-EGFR Ab which demonstrated that tumor sidedness has no significant impact on treatment outcomes in KRASwt mCRC patients receiving second- or later-line therapy. Our findings do not support the utility of tumor sidedness for treatment selection in these settings. We confirmed that patients with right-sided tumors had significantly worse survival.

Vaccine-Related adverse events following AZD1222 (ChAdOx1-nCoV-19) Covid-19 vaccine in solid malignancy patients receiving cancer treatment, as compared to age-matched healthy controls.

The study aimed to evaluate vaccine-related adverse events (VRAEs) following ChAdOx1-nCoV-19 vaccine in solid cancer patients receiving treatment compared to healthy controls. 399 cancer patients and 90 healthy volunteers were enrolled. In the overall population, the incidence of VRAEs was significantly lower in cancer patients than in healthy volunteers (57% vs 80%, P < .001). Because the mean age of the cancer patients was higher than the healthy volunteers (59 vs 48 years, P < .001), we analyzed age-matched comparison and found that there was no significant difference of VRAEs between two groups (74% vs 79%, P .32). Most VRAEs were of mild severity in both groups. The most common local VRAE was pain at the injection site in both groups, and the most common systemic VRAE was fatigue in the cancer cohort, while myalgia was the most common VRAE among the healthy controls. In the cancer cohort, fever was the only VRAE that led to interruption of the cancer treatment (in two cases). Among the cancer treatment types, patients undergoing chemotherapy-containing regimens had a lower likelihood of experiencing VRAEs. In summary, the overall incidence of VRAEs following ChAdOx1-nCoV-19 vaccine in actively treated cancer patients was comparable to healthy controls after adjusting for age. The VRAEs that occurred rarely interfered with the cancer treatment. These findings substantiate that vaccination with AZD1222 is safe in cancer patients undergoing treatment.

Immunogenicity after a Third COVID-19 mRNA Booster in Solid Cancer Patients Who Previously Received the Primary Heterologous CoronaVac/ChAdOx1 Vaccine.

No data regarding the efficacy of a third mRNA vaccine for solid cancer patients previously primed with the heterologous CoronoVac/ChAdOx1 vaccination implemented in Thailand during the shortage of vaccine supply are available. Forty-four cancer patients who previously received the heterologous CoronaVac-ChAdOx1 regimen were boosted with a third mRNA COVID vaccine, either BNT162b2 or mRNA-1273. Anti-RBD IgG was measured immediately before, two weeks after, and four weeks after the third dose. The antibody response was compared to 87 age- and gender-matched cancer patients who were primed with the homologous ChAdOx1/ChAdOx1 regimens. Post-third dose anti-RBD IgG levels significantly increased compared to pre-third dose levels. There was no statistical difference in post-third dose antibody titers or neutralization levels between these two primary series regimens. Treatment with chemotherapy was associated with a lower antibody response compared to endocrine therapy/biologics. Similar antibody levels were observed after a third booster with either BNT162b2 or mRNA-1273 following heterologous CoronaVac/ChAdOx1 vaccination. There was no statistical difference in the immune response following the third-dose vaccination between cancer patients and healthy individuals who received the same heterologous CoronaVac/ChAdOx1 vaccination. In conclusion, a similar degree of enhanced immunogenicity was observed after a third mRNA COVID-19 vaccination in solid cancer patients who previously received the heterologous CoronaVac/ChAdOx1 regimens.

Durability of Immune Response to ChAdOx1-nCoV-19 Vaccine in Solid Cancer Patients Undergoing Anticancer Treatment.

There are limited data available about the durability of the immune response after administration of the widely used adenovirus-vectored ChAdOx1-nCoV-19 vaccine in cancer patients. This prospective longitudinal observational study analyzed follow-up data of immunogenic responses 12 weeks after the second dose of the ChAdOx1-nCoV-19 vaccine in 290 oncological patients compared to healthy controls. The study aimed to assess the persistence of the humoral immune response three months after the second dose, and omicron neutralization was also evaluated. Three months after completion of the second vaccine dose, the geometric mean titer of SARS-CoV-2 binding total Ig statistically decreased by 42% compared to those at 4 weeks, and was lower than that of the healthy control. Six percent of patients became seronegative for anti-RBD total Ig. Only 5% (2 of 40 samples) tested positive for surrogate neutralization against SAR-CoV-2 Omicron BA.2. Across different therapy types, a waning in immunogenicity was observed within three months after the second dose of the ChAdOx1 nCoV-19 vaccine, rendering it insufficient at that point to protect against the SAR-CoV-2 Omicron BA.2 variant.

Immunogenicity of ChAdOx1-nCoV-19 vaccine in solid malignancy patients by treatment regimen versus healthy controls: A prospective, multicenter observational study.

Background: Limited data exists regarding the efficacy of ChAdOx1-nCoV-19 vaccine against Severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) in solid cancer patients. We aimed to assess the immunogenicity of the ChAdOx1-nCoV-19 vaccine and the impact of different anticancer therapies for solid malignancies on immune response. Methods: This prospective, longitudinal observational study of immunogenicity following ChAdOx1-nCoV-19 vaccination among 385 solid cancer patients on active cancer treatment was conducted in two oncology centers. Participants received the first dose between June 18 and July 27, 2021 and the second dose at 8-10 weeks later. Blood samples were evaluated for total immunoglobulins against the receptor-binding of SARS-CoV-2 spike protein (anti-RBD total-Ig) before, and 4-week after the first- and second-doses. The primary endpoint was the geometric mean titers (GMT) of antibody among solid cancer patients compared to healthy controls and the impact of different cancer treatment types. Findings: Among solid cancer patients, the antibody level increased more slowly to significantly lower levels than achieved in healthy controls. The GMT at 4-weeks post-vaccination in cancer vs. healthy were 224.5 U/ml (95%CI 176.4-285.6) vs. 877.1 U/ml (95%CI 763.5-1008), p<0.0001), respectively. For different types of cancer treatments, chemotherapy agents, especially anthracyclines (GMR 0.004; 95%CI 0.002-0.008), paclitaxel (GMR 0.268; 95%CI 0.123-0.581), oxaliplatin (GMR 0.340; 95%CI 0.165-0.484), and immunotherapy (GMR 0.203; 95%CI 0.109-0.381) showed significantly lower antibody response. Anti-HER2, endocrine therapy and 5-fluouracil or gemcitabine, however, had less impact on the immune response. Interpretation: Suboptimal and heterogeneous immunologic responses were observed in cancer patients being treated with different systemic treatments. Immunotherapy or chemotherapy significantly suppressed the antibody response. Funding: Quality Improvement Fund, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society and Center of Excellence in Clinical Virology at Chulalongkorn University and Chulalongkorn Medical Oncology Research Fund.