Safety and efficacy of single-agent adjuvant trastuzumab in older women with early-stage breast cancer.

Abstract

528 Background: Older adults with multiple comorbidities and poor functional status may not be appropriate candidates for chemotherapy. We conducted a phase II trial to examine the safety and efficacy of single-agent Trastuzumab for older women with early stage Human Epidermal Growth Factor Receptor Type 2 (Her2)-positive breast cancer. Methods: This was a single-arm open label multi-institutional clinical trial of adjuvant single-agent Trastuzumab in women aged ≥ 60 years with stage I-III Her2-positive breast cancer who had either declined chemotherapy or were not chemotherapy candidates. Patients received Trastuzumab monotherapy, (8 mg/kg) for cycle 1 followed by (6 mg/kg) every 3 weeks for 12 months. The primary end point was one-year cumulative incidence of symptomatic congestive heart failure with reduced ejection fraction (HFrEF). Secondary endpoints were disease free survival (DFS) and overall survival (OS) at 5 years. Results: Fifty-six patients were enrolled across four centers with a median follow-up period of 5.0 years, (range 0-6.5). The median age was 72.5 years (range 60-90), 64% had stage I disease, 77% had estrogen-receptor positive disease and 82% had node-negative breast cancer. Only two patients had symptomatic congestive HFrEF with a one-year cumulative incidence of 3.6%; (95% confidence interval [CI], 0.09 to 13.8). Five patients had asymptomatic declines in ejection fraction with a one-year cumulative incidence of 9.1%; (95% CI, 3.9 to 20.1). The 5-year DFS was 86.4%; (95% CI, 73.6 to 93.3). Among seven relapses seen, two were due to distant metastatic breast cancer. The 5-year rate of overall survival was 90.2%; (95% CI, 78.1 to 95.8). Among five deaths, one was due to distant metastatic breast cancer. Conclusions: Among older women with stage I-III HER2-positive breast cancer who decline chemotherapy or are not chemotherapy candidates, treatment with her2 targeted therapy only without chemotherapy may offer a reasonable treatment option without an inordinate rate of cardiac toxicity. Clinical trial information: NCT00796978 .

Safety and efficacy of adjuvant subcutaneous trastuzumab in human epidermal growth factor receptor 2-positive early breast cancer: Final results of the SafeHER study

“…Although the primary objective of noninferiority for trastuzumab monotherapy was not met, trastuzumab monotherapy demonstrated a favorable 3-year DFS with fewer AEs and a more favorable health-related quality of life. Studies evaluating trastuzumab monotherapy in older populations [18] and/or those with low-grade tumors [19] showed favorable DFS, suggesting that additional assessments of chemotherapy de-escalation strategies, including HER2-targeted therapies only, for the treatment of HER2-positive EBC are warranted to identify candidates who may benefit from a chemotherapy-free regimen.…”

“…Drug exposure was comparable across all chemotherapy subgroups in the safety population, with a planned 18-cycle treatment regimen. The overall median (range) number of cycles was 18 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) for the no chemotherapy subgroups and 18 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) for both chemotherapy subgroups. Multiple events of the same CTC grade were counted only once in that CTC grade.…”

Adjuvant trastuzumab without chemotherapy for treating early HER2-positive breast cancer in older patients: A propensity score-adjusted analysis of a prospective cohort study

“…Regarding the safety of trastuzumab in older patients, the results of a large observational study indicated that the risk of cardiac function toxicity was 5.7% [ 18 ] and that it was associated with age [ 18 , 19 ], although it remained manageable [ 18 ], and the risks associated with trastuzumab were outweighed by the benefits [ 18 , 20 ]. A phase II study of trastuzumab monotherapy in older women showed that DFS at 5-year was 86.4% (95% CI: 73.6 to 93.3) with cardiac safety [ 21 ]. In terms of the balance between benefit and harm, we recommend trastuzumab monotherapy if the patients do not receive chemotherapy, based on our current findings.…”