Risk Factors for Eribulin-induced Severe Neutropenia in Patients With Recurrent Breast Cancer.

BACKGROUND/AIM: Eribulin is an effective chemotherapeutic agent for advanced and metastatic breast cancer. However, severe neutropenia occurs in 30-40% of patients and interferes with the recommended treatment schedule. Neutropenia is a major cause of treatment interruptions, delays, or even relative dose reductions. This study aimed to examine the risk factors for severe neutropenia after eribulin treatment. PATIENTS AND METHODS: We retrospectively evaluated 263 patients with metastatic breast cancer who had received eribulin therapy. Risk factors for severe neutropenia in the first cycle were evaluated. RESULTS: Severe neutropenia in cycle 1 occurred in 50% of the patients. Multivariate analysis suggested six risk factors for severe neutropenia: low baseline neutrophil count and body mass index, high aspartate aminotransferase and bilirubin levels, creatinine clearance (CrCl) less than 50 ml/min, and eribulin dose of 1.4 mg/m2 Conclusion: This is one of the few studies to simultaneously examine both hepatic and renal functions in relation to severe neutropenia induced by eribulin. We have provided important information to support the close monitoring of patients with these risk factors and subsequent dosage adjustments, if necessary.

Clinical Management of Potential Toxicity of Abemaciclib and Approaches to Ensure Treatment Continuation.

INTRODUCTION: The association between abemaciclib dose reduction and treatment adherence is not clear. In this study, we examined real-world data of Japanese patients with advanced breast cancer (ABC) to determine how abemaciclib dose reduction is related to treatment continuation. METHODS: This retrospective observational study involved 120 consecutive patients with ABC who received abemaciclib from December 2018 to March 2021. The time to treatment failure (TTF) was estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify factors associated with a TTF of >365 days (TTF365). RESULTS: According to the dose reduction during treatment, the patients were classified into 100, 200, and 300 mg/day abemaciclib groups. The 300 mg/day group had a TTF of 7.4 months, whereas the 100 and 200 mg/day groups had significantly longer TTFs (17.9 and 17.3 months, respectively; P = 0.0002). In this study, relative to the 300 mg/day arm, TTF was improved in 200mg/day arm and 100 mg/day arm (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.33-0.93) and [HR], 0.37; 95% CI, 0.19-0.74). For patients who received 300mg/day of abemaciclib dose arm, 200mg/day, and 100mg/day, the median TTF was 7.4 ,17.9 and 17.3 months. The frequently reported adverse effects (AEs) were anemia, increased blood creatinine levels, diarrhea, and neutropenia (90%, 83%, 83%, and 75% of the patients, respectively). Neutropenia, fatigue, and diarrhea were the top AEs causing dose reduction. A multivariate analysis that examined factors associated with achieving TTF 365 confirmed that dose down was an important factor (odds ratio: 3.95, 95% confidence interval: 1.68-9.36, P = 0.002). CONCLUSIONS: In this study, the 100 and 200 mg/day groups had a longer TTF than the 300 mg/day group, and dose reduction was identified as an important factor in achieving longer TTF.

Identifying Early Predictive Markers for Immune-Related Adverse Events in Nivolumab-Treated Patients with Renal Cell Carcinoma and Gastric Cancer.

BACKGROUND: Neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios can indicate poor disease prognosis and are inflammation markers. We investigated the role of NLR and PLR as effective predictive markers of immune-related adverse event (irAE) onset in patients treated with nivolumab. METHODS: We retrospectively analysed 73 gastric and renal cancer patients treated with nivolumab at the Hokkaido Cancer Centre from January 2017 to June 2020. NLR and PLR were calculated at the initiation of nivolumab treatment and irAE onset. We identified the risk factors for Grade 3-4 irAE onset using NLR, PLR, sex, cancer type, and age. Overall survival (OS) and progression free survival (PFS) were calculated from the initiation of nivolumab treatment to the date of death or censored at last follow-up. RESULTS: Among the 73 patients included, 17 (18%) had at least one grade3-4 irAE. Multivariable logistic regression analyses revealed that pretreatment NLR<4.3 was significantly associated with a reduced risk for onset of grade3-4 irAEs, whereas rate of NLR change after treatment, ΔNLR>120% was significantly associated with an increased risk. CONCLUSIONS: NLR is an effective marker for prognosis and onset of grade 3-4 irAEs.

[Factors Contributing to the Occurrence of Edema in Breast Cancer Patients Receiving DTX Treatment].

Edema is a frequent side effect observed in patients receiving docetaxel hydrate(DTX)treatment. However, the factors contributing to the development of edema in breast cancer patients receiving this treatment have not been completely elucidated. In this study, we examined the electronic medical records of breast cancer patients who received 4 courses of DTX ± trastuzumab therapy at the Hokkaido Cancer Center between January 2017 and February 2018 to investigate the occurrence of edema and related factors. We found that edema was confirmed in 23(42.6%)of the 54 surveyed patients. Further, HER2- positive and high BNP levels before the start of treatment were shown to be factors related to edema development. In particular, the results suggested that when DTX is administered in combination with trastuzumab, it is necessary to monitor early and frequently the occurrence of edema.

Axitinib-Induced Hypothyroidism as a Predictor of Long-Term Survival in Patients with Metastatic Renal Cell Carcinoma.

BACKGROUND: The side effects of sunitinib, namely onset of hypertension and hypothyroidism, have been reported to be predictive biomarkers of treatment efficacy. However, the relationship between hypothyroidism and prolongation of survival in treatment with axitinib, a drug similar to sunitinib, has not yet been reported. OBJECTIVE: In this study, we examined the relationship between the onset of hypothyroidism caused by axitinib and overall survival (OS) and progression-free survival (PFS). METHODS: In this retrospective study, 44 Japanese patients, including 30 men and 14 women, were enrolled. The average age of subjects in this study was 67 years. RESULTS: During treatment, 68% of patients developed hypothyroidism, with an average peak thyroid-stimulating hormone (TSH) value of 15.7 mIU/L. Patients with TSH > 4 mIU/L and required thyroid hormone regulation with levothyroxine had prolonged PFS (11.1 vs. 3.5 months; p = 0.002) and OS (26.4 vs. 15.6 months; p = 0.02). Hypothyroidism was found to be a significant side effect of axitinib in patients with metastatic renal cell carcinoma (mRCC). Patients with hypothyroidism had significantly longer PFS and OS. CONCLUSION: Our findings indicate that hypothyroidism may be a predictive marker of therapeutic effect of axitinib against mRCC.

Skin Disorders and Primary Tumor Location as Prognostic Factors in Patients with Metastatic Colorectal Cancer Treated with Cetuximab and Chemotherapy

Background: Cetuximab-induced skin disorder is common in colorectal cancer (CRC), and is known to affect prolonged overall survival (OS). Patients with left-sided CRC survive longer than those with right-sided CRC, among those treated with combination cetuximab and chemotherapy. However, no study has evaluated patient prognosis in terms of OS and progression-free survival (PFS) in relation to both tumor location and skin disorder. This study aimed to determine the incidence of skin disorder according to tumor location and analyze the relationship of tumor location and skin disorder with OS. Methods: Patients with metastatic colorectal cancer (mCRC) treated with standard chemotherapy and cetuximab as first-line therapy were included. Differences in the incidence of skin disorders due to the location of the primary tumors were compared in the same patient. The OS and PFS in relation to the location of the primary tumors and presence or absence of skin disorder were also compared. Results: Total frequency of each skin disorder as rash acneiform, paronychia, and dry skin in patients with left- and right-sided mCRC was 70%, 70%, and 43% and 27%, 36%, and 27%, respectively. The median OS was 8.9 months for mCRC on the left-sided without skin disorder and 56.3 months for mCRC on the left-sided with skin disorder. In comparison, the median OS was 10.4 months for mCRC on the right-sided without skin disorder and 11.3 months for mCRC on the right-sided with skin disease (left-sided with skin disorder versus other three group; P<0.001). Conclusions: Primary tumor location and the presence of skin disorder are important factors in patients with mCRC who receive cetuximab. In particular, our results show the new fact that the left-sided and right-sided mCRC survival time were comparable if there is no skin disorder caused by cetuximab.