Real-world patient characteristics, treatment patterns, and clinical outcomes associated with tucatinib therapy in HER2-positive metastatic breast cancer.

Background: Tucatinib is an oral human epidermal growth factor receptor 2 (HER2)-directed therapy approved in combination with trastuzumab and capecitabine for use in patients with previously treated HER2+ metastatic breast cancer (MBC) with/without brain metastases (BM). To inform clinical decision-making, it is important to understand tucatinib use in real-world clinical practice. We describe patient characteristics, treatment patterns, and clinical outcomes for tucatinib treatment in the real-world setting. Methods: This retrospective cohort study included patients diagnosed with HER2+ MBC (January 2017-December 2022) who received tucatinib treatment in a nationwide, de-identified electronic health record-derived metastatic breast cancer database. Patient demographics and clinical characteristics were described at baseline (prior to tucatinib initiation). Key outcomes included real-world time to treatment discontinuation (rwTTD), time to next treatment (rwTTNT), and overall survival (rwOS). Results: Of 3,449 patients with HER2+ MBC, 216 received tucatinib treatment (n=153 with BM; n=63 without BM) and met inclusion criteria. Median (range) age of patients was 56 (28-84) years, 57.9% were White, and 68.5% had Eastern Cooperative Oncology Group performance status ≤1. Median (IQR) follow-up from start of tucatinib treatment was 12 (6-18) months. Among all patients who received tucatinib treatment, median (95% CI) rwTTD was 6.5 (5.4-8.8) months with 39.8% and 21.4% remaining on treatment at 12 and 24 months, respectively. Median (95% CI) rwTTNT was 8.7 (6.8-10.7) months. Patients who received the approved tucatinib triplet combination after ≥1 HER2-directed regimen in the metastatic setting had a similar median (95% CI) rwTTD (any line: 8.1 [5.7-9.5] months; second-line (2L) and third-line (3L): 9.4 [6.3-14.1] months) and rwTTNT (any line: 8.8 [7.1-11.8] months; 2L and 3L: 9.8 [6.8-14.1] months) to the overall population. Overall, median (95% CI) rwOS was 26.6 (20.2-not reached [NR]) months, with similar findings for patients who received the tucatinib triplet (26.1 [18.8-NR] months) and was NR in the subgroup limited to the 2L/3L population. Conclusion: Tucatinib treatment in the real-world setting was associated with a similar median rwTTD, rwTTNT, and rwOS as in the pivotal HER2CLIMB trial, with particular effectiveness in patients in the 2L/3L setting. These results highlight the importance of earlier use of tucatinib in HER2+ MBC.

IL-4 biology: impact on normal and leukemic CLL B cells.

This review provides a perspective on the role of IL-4 in relation to both normal and leukemic CLL B cells. IL-4 is a well-characterized cytokine known to be produced by normal T cells and have impact on normal B cell differentiation and proliferation. This cytokine and its receptor are now known to exist on CLL B cells. An autocrine pathway for CLL B cells is strongly supported by signaling events, alteration of apoptotic proteins and changes in apoptosis resistance. Based on the increasing knowledge regarding the IL-4 pathway unique opportunities for therapy are now available in B-CLL.

Antimicrobial susceptibility trends in Campylobacter jejuni and Campylobacter coli isolated from a rural Egyptian pediatric population with diarrhea.

Comparative and trend analysis was conducted on annual prevalence of antimicrobial susceptibility among Campylobacter jejuni and Campylobacter coli recovered from rural Egyptian children from 1995 through 2000. C. jejuni and C. coli demonstrated significant decreasing trends in ciprofloxacin susceptibility over the study period (p < 0.001 for both). In general, C. coli demonstrated a higher degree of susceptibility than C. jejuni, however, there was no statistical difference (p = 0.2) comparing the linear trends over the duration of the study. There was no indication of frank macrolide (erythromycin or azithromycin) resistance among any Campylobacter. Moreover, there were statistically significant positive trends in both the MIC(50) and MIC(90) values for the erythromycin and azithromycin during the study period, suggesting a possible decreasing trend in susceptibility among Campylobacter. This study demonstrated that antimicrobial susceptibility in Campylobacter has significantly decreased from 1995 through 2000 among pediatric diarrhea cases in rural Egypt.