Purpose Significant improvement in survival outcomes has been established with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2) –positive early breast cancer treatment. However, trastuzumab may increase the risk of cardiac toxicity, and long-term evaluation of its incidence and risk factors are warranted. Methods NCCTG (Alliance) N9831 trial compared adjuvant doxorubicin and cyclophosphamide (AC) followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or paclitaxel plus trastuzumab followed by trastuzumab alone (arm C) in patients with HER2-positive breast cancer. Cumulative incidence of cardiac events (CE) and left ventricular ejection fraction (LVEF) were evaluated in 1,944 women who proceeded to post-AC therapy. Risk factors for trastuzumab-induced cardiac toxicity were identified by Cox regression models. Results The 6-year cumulative incidence of CE was 0.6% in arm A, 2.8% in arm B, and 3.4% in arm C. At a median follow-up of 9.2 years, only two additional CHF diagnoses (of 1,046 patients) occurred beyond our previously reported follow-up time of 3.75 years. LVEF recovered in the majority of the patients who developed CHF. There were two cardiac deaths in arm A and one each in arms B and C. Age of 60 years or older, registration LVEF less than 65%, and use of antihypertensive medications were associated with an increased risk of CE in arms B and C. Conclusion The cumulative incidence of CE at 6 years was slightly higher with the addition of trastuzumab; however, the late development of CE is infrequent. Trastuzumab (in the context of anthracycline- and taxane-based therapy) continues to have a favorable benefit-risk ratio.
Outcomes have improved considerably in multiple myeloma (MM), but disparities among racial‐ethnic groups exist. Differences in utilization of novel therapeutics are likely contributing factors. We explored such differences from the SEER‐Medicare database. A utilization analysis of lenalidomide, thalidomide, bortezomib, and stem cell transplant (SCT) was performed for patients diagnosed with MM between 2007 and 2009, including use over time, use by race, time‐dependent trends for each racial subgroup, and survival analysis. A total of 5338 MM patients were included with median 2.4‐year follow‐up. Within the first year of MM diagnosis, utilization of lenalidomide, bortezomib, SCT, and more than one novel agent increased over time while utilization of thalidomide decreased. There was significantly lower utilization of lenalidomide among African‐Americans (P < 0.01), higher thalidomide use among Hispanics and Asians (P < 0.01), and lower bortezomib use among Asians (P < 0.01). Hispanics had the highest median number of days to first dose of bortezomib (P = 0.02) and the lowest utilization of SCT (P < 0.01). Hispanics and Asians were the only groups without notable increases in lenalidomide and bortezomib use, respectively. SCT utilization increased over time for all except African‐Americans. SCT use within the first year after diagnosis was associated with better overall survival (HR 0.52; 95% CI: 0.4–0.68), while bortezomib use was associated with inferior survival (HR 1.14; 95% CI 1.02–1.28). We noted considerable variability in MM therapeutics utilization with seeming inequity for racial‐ethnic minorities. These trends should be considered to eliminate drug access and utilization disparities and achieve equitable benefit of therapeutic advances across all races.
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