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Background Oral cancer therapy-related cardiovascular (CV) toxicity has a wide variety of presentations including arrhythmia, cardiomyopathy, and myocardial infarction, but clinical evidence related to its management is limited. The purpose of this IRB-approved, single-center, retrospective, cohort study was to characterize cardio-oncologic interventions for CV adverse events related to oral oncolytics. Methods The cohort included 67 patients who were admitted to a multi-hospital health system between June 1, 2016 and July 31, 2021, had at least one medical record order of oral oncolytics considered to have cardiotoxic potential, and had an ICD10 code for a cardiotoxic event added to their electronic medical records after initiation of oral oncolytics. Results The majority (97%) had pre-existing cardiovascular disease (CVD) or a CV risk factor. The three most common classes of oral oncolytics were aromatase inhibitors (36%), BCR-ABL inhibitors (16%), and VEGFR inhibitors (13%). New-onset or worsening heart failure (HF) ( n  = 31), which occurred after a median of 148 days (Interquartile range (IQR) 43–476 days) was the most common cardiotoxic event. The most frequent interventions were pharmacological treatment of the CV adverse event ( n  = 44) and treatment interruption ( n  = 18), but guideline-directed medication therapy for HF could be further optimized. Conclusion Pre-existing CVD or CV risk factors predispose oncology patients to CV adverse events. Real-world practice reveals that CV adverse events require temporary interruption of treatment and initiation of pharmacologic treatment. A multidisciplinary, patient-centered approach that includes discussion of risks/benefits of treatment continuation, and initiation of guideline-directed treatment is recommended until high-quality, drug-specific data for monitoring and treatment become available.

Background: Colorectal carcinoma (CRC) is one of the most common cancer types along with breast, prostate, and lung cancer. Many patients with CRC present with metastatic disease despite receiving standard first- and second-line therapies; thus emerges the demand for implementing new therapies that could improve outcomes among CRC patients. This case series was conducted to assess the efficacy and safety of regorafenib plus 5-fluorouracil (5-FU) in patients with refractory metastatic CRC (mCRC). Methods: We conducted a retrospective analysis of data from adult patients aged 18 and above who were diagnosed with refractory mCRC and received regorafenib plus 5-FU combination therapy at Houston Methodist Hospital between November 2017 and October 2023. Our study focuses on assessing key outcomes, including Overall Survival [OS], Progression-Free Survival [PFS], and safety. Results: Among the 12 patients we included in this study who underwent regorafenib plus 5-FU combination therapy for refractory mCRC after receiving at least three prior lines of treatment, the best response for six patients (50%) was successfully achieved, with disease control within 7–12 weeks from therapy initiation. Patients had an overall good tolerance for this treatment regimen and reported only the most common adverse events, including Hand-Foot Syndrome (HFS), mucositis, and hypertension (HTN), which were mostly resolved with dose adjustment of medications. Conclusions: This study highlights that using a combination of regorafenib plus 5-FU can be a potential treatment option for patients with refractory mCRC. Additional research, including prospective clinical trials, is required to assess the effectiveness and safety of regorafenib and 5-FU combination therapy in comparison to other currently limited treatment options.

Oncology drug shortages have significant implications on patient care, particularly with curative intent therapeutic strategies. This case series highlights strategic management for patients with classical Hodgkin lymphoma (cHL) in the setting of recent dacarbazine and vinblastine shortages without compromising outcomes. cHL is a highly curable malignancy with initial treatment strategies incorporating chemotherapy, radiation therapy, chemoradiotherapy, or chemoimmunotherapy. The standard of care for patients with cHL includes a backbone of doxorubicin, vinblastine, and dacarbazine (AVD) based therapies in combination with either bleomycin, brentuximab vedotin (BV), or nivolumab. However, in 2023, critical shortages of dacarbazine and vinblastine led to rationing of these agents, raising concerns for a paucity of clear management strategies in patients with cHL. The three patients described in this case series received lower cumulative doses of standard chemotherapy as opposed to alternative therapies without compromising outcomes. Treatment of advanced stage cHL during dacarbazine and vinblastine shortage requires careful consideration of alternative therapies and collaborative effort among healthcare professionals. This case series highlights that with a response-added approach and vigilant monitoring, effective cancer treatment strategies may be implemented despite drug shortages.

BackgroundThe therapeutic landscape of unresectable Hepatocellular carcinoma (uHCC) continues to evolve. Atezolizumab, an anti-programmed cell death ligand 1 (PD-1) immune checkpoint inhibitor (ICI) in combination with bevacizumab have substantially improved outcomes. While immune-related adverse events are a well-known complication of ICIs, infections, a common complication impacting morbidity and mortality in patients receiving systemic myelosuppressive chemotherapies, is seldom reported. The aim of this study is to evaluate the incidence, risk factors, and outcomes in patients who develop infections while receiving Atezolizumab and Bevacizumab for HCC.MethodsPatients who received Atezolizumab/Bevacizumab for uHCC from 1/9/2017–12/28/2022 at a single hospital network were included. Covariates compared among infected and non-infected cohorts included age, sex, race, comorbidities, ECOG, immunosuppressive use, chronic infections, antibiotic or antiviral therapies at ICI initiation, and line of therapy (1L, 2L, >2L). Outcome measures compared included the number of emergency department (ED), hospital, and intensive care unit (ICU) admissions, number of cycles received, median overall survival (OS), and progression-free survival (PFS). Fisher’s exact test for categorical variables and Mann-Whitney test for continuous variables were used to compare cohorts. Kaplan-Meier methodology compared OS and PFS. All analyses were deemed statistically significant if the p-value was <0.05.ResultsOf 810 evaluable patients, a total of 34 patients who had uHCC were treated with Atezolizumab. The mean±SD age was 66.29±9.39, and 28 (82.35%) were males. Infection was reported in 17 (50%) patients, with bacteremia reported in 3 (17.6%) and COVID-19 reported in 4 (23.5%). Infected vs non-infected received a median of 12 (5–17) vs 4 (3–12) ICI cycles (p= 0.18). Baseline demographics did not contribute to infectious risk. The number of ED visits and inpatient hospitalizations was not significant; however, ICU admissions were significantly higher in the infected vs non-infected group (5 (29.41%) vs 0(0.0%)) (p= 0.44). Infections did not negatively impact OS or PFS but resulted in treatment delays and discontinuation in 11 (64.71%) and 7 (41.18%) patients, respectively. At the last follow-up, 19 (55.88%) patients died, 9 (52.94%) non-infected group vs 10 (58.82%) in the infected group (p= 1.0).ConclusionsWhile a broad array of infections occurred in 50% of the patients of this cohort, it did not negatively impact survival outcomes. However, it did impact morbidity with a higher number of all-cause admissions and treatment delays. Infection rates should be included in prospective studies.

BackgroundImmune checkpoint inhibitor (ICI)-based regimens including pembrolizumab/axitinib (P/A), nivolumab/cabozantinib (N/C), and nivolumab/ipilimumab (N/I) have improved outcomes in patients with RCC. While immune related adverse events are a well-known complication contributing to treatment delays, discontinuation, and morbidity, little is reported on the incidence and outcomes of infections. This study aims to assess the incidence, risk factors, and outcomes of infections occurring in patients with RCC receiving ICIs.MethodsData was collected from 7 hospitals for patients who received P/A, N/C, or N/I for RCC from 1/2017–8/2021. Date of last follow-up was 12/2022. Covariates compared among infected and non-infected cohorts included age, gender, race, comorbidities, and ECOG. Risk factors for infection were assessed by univariable analysis with reported odds ratio (OR) and 95% confidence interval (CI). Outcome measures included all-cause emergency department (ED) visits, inpatient, and intensive care unit (ICU) admissions, median number of ICI cycles, progression free survival (PFS) and overall survival (OS). OS/PFS were evaluated using the Kaplan-Meier model. P-value <0.05 was considered statistically significant.ResultsThere were 149 patients included; 54 (36.24%), 34 (22.82%), and 61 (40.94%) received P/A, N/C, N/I, respectively. At least one infection was documented in 51 (34.2%) patients, of which 18 (35.29%), 12 (23.53%), 21 (41.18%) received P/A, N/C, N/I, respectively. There was no statistically significant difference in infectious risk between the three regimens. ECOG >1 (OR 6.22, [95% CI 1.92, 19.73], p=0.002) was associated with higher risk of developing infections. Infected patients had a higher rate of ED (14 (27.45%) vs 13 (13.27%), p= 0.033), inpatient (40 (78.43%) vs 42 (42.86%), p<0.001), and ICU admissions (13 (25.49%) vs 2 (2.04%), p< 0.001) than non-infected, and trended toward both a shorter PFS (7.27 [95% CI 4.97–16.43] vs 11.5 [95% CI 6.23–36.33], p=0.36) and OS (9.97 [95% CI 5.5–32.53] vs not reached, p=0.10), respectively. Infections did not impact number of cycles received compared to non-infected (5 [3–15] vs 4 [3–16], p=0.86). At last follow-up, there was a higher proportion of all-cause deaths in the infected vs non-infected cohort (28 [54.90%] vs (37 [37.76%], p=0.045); of these 17 (60.71%), 5 (17.86%), 5 (17.86%), and 1 (3.57%) died due to primary disease, infection, multiorgan failure, and ‘other’, respectively.ConclusionsInfections in patients receiving ICIs for metastatic RCC are common and the risk is similar across regimens. Infections are associated with a higher hospitalization rate, all-cause mortality, and trend toward poorer survival. Strategies to minimize infectious processes to optimize outcomes are needed.

BackgroundWhile infections are a known cause of morbidity and mortality in those receiving chemotherapy, the burden of infections in the ICI era is seldom explored. This analysis aimed to assess incidence of infections and risk factors in patients who received pembrolizumab (P), nivolumab (N), nivolumab/ipilimumab (N/I), or atezolizumab (A)-based therapies for NSCLC.MethodsData was collected from 7 hospitals for patients who received P, N, N/I, or A for NSCLC from 1/2017–8/2021. Date of last follow up was 12/2022. Covariates compared among infected and non-infected cohorts included age, gender, race, comorbidities, ECOG, chronic infections, and anti-infective at ICI initiation. Outcomes included rate of infection, association of infection between different ICIs, number of cycles received, all-cause emergency department (ED), hospital, and intensive care unit (ICU) admissions, and median overall survival (OS) and progression free survival (PFS). OS/PFS were evaluated using the Kaplan-Meier model. P-value <0.05 was considered statistically significant.ResultsThere were 340 patients included: 243 (71.5%), 53 (15.6%), 15 (4.4%), and 29 (2.5%) received P, N, N/I, and A, respectively. Infection was reported in 146 (42.94%) patients; 111 (45.7%), 23 (43.4%), 2 (13.3%), and 10 (34.5%) received P, N, N/I, and A, respectively. Patients with COPD (OR 1.94 [95% CI 1.19, 3.15], p=0.007) and anti-infectives at ICI initiation (OR 2.99 [95% CI 1.34, 6.66], p=0.007) had a higher risk of infection. Compared to non-infected, infected patients had more ED (48 (32.88%) vs 40 (20.62%) p=0.011), hospital, (115 (78.77%) vs 74 (38.14%) p<0.001), and ICU admissions (37 (25.34%) vs 7 (3.61%) p<0.001). Median OS for infected vs non-infected was 11.87 (95% CI 7.97–17.3) vs 17.6 (95% CI 13.67–21.1) (p=0.286) months and PFS was 6.5 (95% CI 5.1–9.1) vs 7.1 (95% CI 6.2–8.9) (p=0.859) months, respectively. At last follow up, 100 (69.49%) infected and 116 (59.79%) non-infected died; 18 (18%) vs 4 (3.45%) deaths from infection, 13 (13.0%) vs 5 (4.31%) deaths from multiorgan failure, and 63 (63.0%) vs 100 (86.21%) deaths from primary disease (p<0.001), and 6 (6.0%) and 7 (6.03%) dying from other causes.ConclusionsWhile infections appear to be frequent in patients receiving ICI for NSCLC, a smaller proportion are in the setting of non-P ICI regimens. Patients with COPD or who received anti-infectives at ICI initiation had a higher risk of infection. Infections contributed to higher all-cause hospitalization rate and mortality rate, but did not significantly impact survival. Studies to minimize infectious risk to improve patient morbidity and mortality are needed.

The rationale for administering immune checkpoint inhibitors (ICIs) in the adjuvant setting is to eradicate micro-metastases and, ultimately, prolong survival. Thus far, clinical trials have demonstrated that 1-year adjuvant courses of ICIs reduce the risk of recurrence in melanoma, urothelial cancer, renal cell carcinoma, non-small cell lung cancer, and esophageal and gastroesophageal junction cancers. Overall survival benefit has been shown in melanoma while survival data are still not mature in other malignancies. Emerging data also show the feasibility of utilizing ICIs in the peri-transplant setting for hepatobiliary malignancies. While ICIs are generally well-tolerated, the development of chronic immune-related adverse events, typically endocrinopathies or neurotoxicities, as well as delayed immune-related adverse events, warrants further scrutiny regarding the optimal duration of adjuvant therapy and requires a thorough risk–benefit determination. The advent of blood-based, dynamic biomarkers such as circulating tumor DNA (ctDNA) can help detect minimal residual disease and identify the subset of patients who would likely benefit from adjuvant treatment. In addition, the characterization of tumor-infiltrating lymphocytes, neutrophil-to-lymphocyte ratio, and ctDNA-adjusted blood tumor mutation burden (bTMB) has also shown promise in predicting response to immunotherapy. Until additional, prospective studies delineate the magnitude of overall survival benefit and validate the use of predictive biomarkers, a tailored, patient-centered approach to adjuvant ICIs that includes extensive patient counseling on potentially irreversible adverse effects should be routinely incorporated into clinical practice.

Background: The therapeutic landscape of unresectable hepatocellular carcinoma (uHCC) continues to evolve. Atezolizumab, an anti-programmed cell death ligand 1 (PD-1) immune checkpoint inhibitor (ICI), in combination with bevacizumab, has substantially improved outcomes. This study aims to evaluate the incidence, risk factors, and outcomes in patients who develop infections while receiving atezolizumab and bevacizumab for uHCC. Methods: Patients who received atezolizumab and bevacizumab for uHCC at a single hospital network were included. Types and rates of infections were reported. Covariates compared among infected and non-infected cohorts included age, sex, race, comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status, immunosuppressive use, chronic infections, number of cycles of ICIs given, antibiotic or antiviral therapies at ICI initiation, and line of therapy (first-line, second-line, greater than second-line). Results: Out of 810 evaluable patients, 34 uHCC patients were treated with atezolizumab plus bevacizumab. The mean ± SD age was 66.29 ± 9.39; 28 (82.35%) were males. There were 17 (50%) patients with reported infection, with bacterial infection occurring in 12 (70.59%) patients and COVID-19 in 4 (23.5%). Of the infected patients, eight (47.06%) had one infection, five (29.41%) had two infections, and two (11.76%) had three or more infections. Infected and non-infected patients received a median of 12 (IQR: 5–17) and 4 (IQR: 3–12) ICI cycles (p = 0.18), respectively. Infections did not negatively impact OS or PFS but resulted in treatment delays and discontinuation in 11 (64.71%) and 7 (41.18%) patients, respectively. At the last follow-up, 19 (55.88%) patients died, 9 (52.94%) in the non-infected group vs. 10 (58.82%) in the infected group (p = 1.0). Conclusions: While a broad array of infections occurred in 50% of the patients in this cohort, it did not negatively impact survival outcomes. However, it did impact morbidity, with more all-cause admissions and treatment delays.

Background: Immune checkpoint inhibitor (ICI) therapy has significantly improved outcomes across a range of malignancies. While infections are a well-known contributor to morbidity and mortality amongst patients receiving systemic chemotherapy regimens, little is known about the impact of infections on patients receiving ICI therapy. This study aims to assess incidence, risk factors, and outcomes in patients who develop infections while on pembrolizumab-based therapies for non-small cell lung cancer (NSCLC). Methods: Patients receiving pembrolizumab for stage III/IV NSCLC from 1/1/2017-8/1/2021 across seven hospitals were identified. Incidence and type of infection were characterized. Covariates including baseline demographics, treatment information, treatment toxicities, and immunosuppressive use were collected and compared between infected and non-infected patients. Outcomes included the rate of infections, all-cause hospital admissions, median number of treatment cycles, overall survival (OS), and progression free survival (PFS). Univariable and multivariable analysis with reported odds ratio (OR) and 95% confidence intervals (CI) were utilized to evaluate infection risks. OS and PFS were analyzed by Kaplan–Meier analysis and tested by log-rank test. p-value < 0.05 was considered statistically significant. Results: There were 243 NSCLC patients that met the inclusion criteria. Of these, 111 (45.7%) had one documented infection, and 36 (14.8%) had two or more. Compared to non-infected patients, infected patients had significantly more all-cause Emergency Department (ED) [37 (33.3%) vs. 26 (19.7%), p = 0.016], hospital [87 (78.4%) vs. 53 (40.1%), p < 0.001], and ICU visits [26 (23.4%) vs. 5 (3.8%), p < 0.001], and had poorer median OS (11.53 [95% CI 6.4–16.7] vs. 21.03 [95% CI: 14.7–24.2] months, p = 0.033). On multivariable analysis, anti-infective therapy (OR 3.32, [95% CI: 1.26–8.76], p = 0.015) and ECOG of >1 (OR 5.79, [95% CI 1.72–19.47], p = 0.005) at ICI initiation conferred an increased risk for infections. At last evaluation, 74 (66.7%) infected and 70 (53.0%) non-infected patients died (p = 0.041). Conclusion: Infections occurred in nearly half of patients receiving pembrolizumab-based therapies for NSCLC. Infected patients had frequent hospitalizations, treatment delays, and poorer survival. ECOG status and anti-infective use at ICI initiation conferred a higher infection risk. Infection prevention and control strategies are needed to ameliorate the risk for infections in patients receiving ICIs.