Analysis of Efficacy and Tolerability of Bruton Tyrosine Kinase Inhibitor Ibrutinib in Various B-cell Malignancies in the General Community: A Single-center Experience.

BACKGROUND: Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a novel drug that has shown significant efficacy and survival benefit for treatment of various B-cell malignancies. The primary objective of the present study was to investigate the efficacy of ibrutinib therapy in various B-cell malignancies in the general community. The secondary objectives included studying the adverse effects, ibrutinib-induced peripheral lymphocytosis, and effect on immunoglobulin levels. PATIENTS AND METHODS: The present study was a retrospective observational cohort analysis conducted at Abington Jefferson Health. The clinical response was determined from the hematologist's assessment and evaluated independently using the response criteria for each B-cell malignancy. Adverse effects were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The Wilcoxon signed-rank test was used to compare immunoglobulin levels before and after ibrutinib. Forty five patients with B-cell malignancies and receiving ibrutinib therapy were eligible. RESULTS: The median age was 73 years (range, 49-96 years), and 84.4% of the patients had received ≥ 1 previous therapy. The best overall response rate of all cohorts combined was 63.8%. The greatest overall response rate was observed in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (76.1%), followed by those with Waldenström macroglobulinemia (75%). Of the 45 patients, 88.9% experienced adverse effects. Antiplatelet activity of ibrutinib was most commonly observed (30.5%). Of note, 5 patients (11%) developed new-onset atrial fibrillation after drug initiation. Peripheral lymphocytosis after drug initiation was observed in most patients, with a peak level at 1 month (median lymphocyte count, 2.7 × 103 cells/µL). Although the IgG levels at 3, 6, and 12 months had decreased (P = .01 for all) compared with the levels before ibrutinib, the IgA levels had not increased at 3, 6, 12, and 24 months (P = .6, P = .5, P = .3, and P = .9, respectively). CONCLUSION: Ibrutinib is a highly effective and tolerable drug for B-cell malignancies in the general community. In contrast to the previously reported rate of 5% to 7%, we observed a higher rate (11%) of atrial fibrillation, which might have resulted from the smaller sample size in the present study and the multiple comorbidities. Nonetheless, this treatment-limiting side effect requires further elucidation. Paradoxical lymphocytosis at the outset of therapy was a common and benign finding. In conjunction with the reported trials, the IgG levels decreased in the first year of continued therapy. However, the IgA levels did not increase, even after 2 years of therapy.

Chemotherapy Significantly Improves Survival for Patients with T1c-T2N0M0 Medullary Breast Cancer: 3739 Cases From the National Cancer Data Base.

BACKGROUND: Medullary breast cancer (MBC) is a rare tumor associated with a better prognosis compared with other breast cancers. The role of adjuvant chemotherapy has not been extensively studied. METHODS: Female patients with invasive MBC reported to the National Cancer Data Base from 2004 to 2012 were analyzed. Overall survival (OS) and treatment were studied using the Kaplan-Meier method and the Cox proportional hazard model. Patients who had node-negative (N0), non-metastatic (M0) tumors 10 to 50 mm in size (T1cN0M0 and T2N0M0) treated with and without chemotherapy were analyzed using propensity score matching. RESULTS: Of 3739 patients with MBC, 2642 (71%) had T1b-T2N0M0 disease treated with and without chemotherapy. Multivariable analysis showed that for all MBC patients, the significant predictors of OS were age older than 65 years, one or more comorbidities, tumor larger than 2 cm, positive nodes, distant metastasis, and treatment with chemotherapy or radiation therapy. Patients with T1cN0M0 and T2N0M0 had improved OS if they received chemotherapy (p < 0.0005). Patients with T1bN0M0 who received chemotherapy did not show better OS than those who did not. Patients with T1c-T2N0M0 were then matched by propensity score based on age, presence of comorbidities, tumor size, and treatment methods used. After matching, the group receiving chemotherapy showed an improved OS (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.26-0.62; p < 0.0005) compared to the group that did not receive chemotherapy. CONCLUSIONS: For patients with T1c-T2N0M0 MBC, chemotherapy significantly improves OS.

Atypical medullary carcinoma of the breast has similar prognostic factors and survival to typical medullary breast carcinoma: 3,976 cases from the National Cancer Data Base.

BACKGROUNDS AND OBJECTIVES: Medullary breast carcinoma (MBC) is a subtype with a more favorable prognosis. Tumors with some, but not all, characteristics of MBC are classified as atypical medullary carcinoma of the breast (AMCB). METHODS: Patients with invasive MBC and AMCB reported to the National Cancer Data Base (NCDB) from 2004 to 2013 were compared for tumor characteristics and overall survival, using infiltrating ductal carcinoma (IDC) as a reference. RESULTS: Patients with MBC (n = 3,688), AMCB (n = 288), and IDC (n = 918,870) met inclusion criteria. Comparing MBC with AMCB, the mean age at diagnosis (52.9 vs. 53.9 years), mean tumor size (2.4 vs. 2.5 cm), lymph node positivity (22.8% vs. 22.4%), estrogen receptor (ER) positivity (22% vs. 25%), progesterone receptor (PR) positivity (14% vs. 15%), HER2 positivity (11% vs. 14%), rate of breast conserving surgery (67% vs. 68%), use of chemotherapy (76% vs. 75%), and use of hormonal therapy (19% vs. 18%), respectively, were not clinically or statistically different. Five-year (92% vs. 89%) and 10-year survival rates (85% vs. 87%) were not significantly different (P = 0.46). CONCLUSIONS: There does not appear to be any reason to differentiate between AMCB and MBC given the similarities in presentation, treatment and prognosis. J. Surg. Oncol. 2016;114:533-536. © 2016 Wiley Periodicals, Inc.

Rhabdomyolysis resulting from pharmacologic interaction between erlotinib and simvastatin.

Erlotinib is an epidermal growth factor receptor inhibitor indicated as a second line of therapy for locally advanced and metastatic non-small-cell lung cancer after the failure of 1 previous chemotherpy. Simvastatin belongs to the statin family used to lower blood cholesterol. Drug interaction between erlotinib and statin has not been reported before. Both drugs are major substrates of the CYP3A4 enzyme in the liver. Thus, co-administration of these drugs can increase their serum levels, potentially leading to adverse effects. We report the interaction between erlotinib and simvastatin leading to rhabdomyolysis. Thus, caution is required with increasing usage of both of these drugs.

Changing patterns of bone and brain metastases in patients with colorectal cancer.

BACKGROUND: Therapeutic advances for patients with metastatic colorectal cancer (CRC) have been associated with prolonged survival. This study was undertaken to test the hypothesis that expanded treatment options and resultant improved survival for patients with metastatic CRC are associated with an increased incidence of metastases at uncommon sites. PATIENTS AND METHODS: Patients with metastatic CRC evaluated from 1993 to 2002 at the Fox Chase Cancer Center were identified. Medical records were abstracted to obtain the following: date of diagnosis/metastasis, primary tumor site, therapeutic agents received, survival, and site(s) of metastases. RESULTS: The records of 1020 patients were reviewed. Incidence of bone and brain metastases were 10.4% (95% CI, 8.6%-12.4%) and 3% (95% CI, 2.2%-4.5%), respectively. Bone metastases were more common with increased numbers of active systemic agents received: 0 (3.7%), 1 (9.4%), 2 (10.9%), 3 (16.3%), and 4/5 (17.4%; P = 0.001; trend test). Patients receiving irinotecan or oxaliplatin were more likely to develop bone metastases (13.2% vs. 8.3%, P = 0.01 for irinotecan; 16.9% vs. 9%, P = 0.003 for oxaliplatin). Patients with primary rectal versus primary colon cancer were more likely to develop bone metastases (16% vs. 8.6%; P = 0.001). Patients with lung metastases were more likely to have bone metastases (16.1% vs. 6.4%; P < 0.0001) or brain metastases (6.2% vs. 1.2%; P < 0.0001) than those without. CONCLUSION: These data demonstrate that the incidence of bone and brain metastases in patients with CRC is more common than previously reported and is associated with receipt of multiple systemic treatments. As survival improves for this patient population, clinicians should be aware of the potential for metastases at previously uncommon sites.