To our knowledge, our population of elderly patients treated with adjuvant trastuzumab is the largest analyzed so far. The beneficial long-term results were comparable to those in the younger cohorts. Although the risk of cardiotoxicity increased significantly with age, it also remained manageable in older patients. Thus, chronological age alone should not preclude HER2 antibody treatment.

Purpose: Trastuzumab (T; Roche) is part of the standard treatment in patients (pts) of any age with early stage, HER2+ breast cancer, in addition to (neo)adjuvant chemotherapy (CT) and locoregional treatment. After its registration in Germany in 2006, this prospective observation study was started in order to assess the generalizability of the results from the randomized studies, specifically with respect to elderly age cohorts. Methods: 4027 pts were enrolled between 2006 and 2012. 87 were non-eligible due to M1 and/or negative HER2 status. There were no restrictions for recruitment with respect to age or concomitant/sequential adjuvant medication. The long-term relapse/survival status of pts was retrieved by fax forms collected once a year. Safety assessment was limited to the treatment period. Data base cut-off was May 2013. Results: Among the 3940 evaluable pts, there were 1013 elderly pts (EP) ≥ 65 years (y) of age (26%). This contrasts to the pivotal studies, e.g. with a proportion of only 6% beyond 65 y in the NSABP B-31 and NCCTG N9831 studies. The rate of EP steadily increased during the period from 2006 to 2009, remaining stable thereafter. More than half of the pts had pT≥2, with EP more often presenting with a larger tumor (56% vs. 48%,p<.0001). 52% had a grade 3 tumor. Hormone receptor positivity was recorded in 63%. As to be expected, performance status was more impaired in elderly compared to younger pts (ECOG 0: 53 vs 65%,p<.0001). 94% received CT, 78% as adjuvant, 14% as neoadjuvant treatment (in EP only 8%), while 2% received both modalities. In the vast majority (87%), T was administered sequentially to CT, with no differences among the age cohorts. The proportion without any adjuvant CT was higher in EP (8 vs. 5%). 56% of pts were treated with adjuvant endocrine medication, 78% with irradiation. T treatment was stopped prematurely in only 9% of pts, but more often in EP (11% vs 8%, p = .014). After a follow-up period of up to a maximum of 8 y, 370 relapses were reported so far. The estimated recurrence-free survival is 94.7% (95% CI: 94-96%), 89.8% (89-91%), and 82.9% (81-85%) after 2, 3 and 5 y, respectively. Numeric results in EP are only slightly lower with 93.9 (92-96%), 89.3% (87-92%), and 81.6% (78-85%), not statistically significant (p = 0.18, HR = 1.17 [95% CI: 0.93 - 1.47]). Adverse effects with respect to cardiac function were reported in overall 153 pts (3.9%), with the majority of these cases of NCI grade 1 (39%) or 2 (38%). 23% of these events were of grade 3/4, but life-threatening in only 2 pts. Thus, the overall incidence of acute grade 3/4 cardiac function toxicity was 0.9%. In the EP subgroup the incidence across all NCI grades was only slightly increased (4.6%), but grade 3/4 cases were more common (1.6%). Conclusion: Overall, the maturing follow-up data of this observational study confirm the beneficial results from the randomized studies. In addition, the data from more than thousand pts ≥ 65 y of age show that a similar anti-tumor efficiency can be achieved in elderly pts, and suggest that minor age-related differences detected with respect to adjuvant treatment duration, aggressiveness and toxicity do not impair the long-term clinical outcome. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-15-02.

Background: Trastuzumab (T) is approved in most Western countries for the treatment of early, HER2+ breast cancer (BC) parallel or sequential to adjuvant chemotherapy (CT). Nevertheless, as in metastatic disease, the antibody seems to be used without chemotherapy in a selected group of HER2+ patients (pt). The purpose of this analysis is to characterize this subgroup as well as describe safety and efficacy outcome parameters in this German prospective observation trial. Methods: At present, 2870 patients (pts) have been enrolled and documented in this ongoing non-interventional study from 270 German centers. At data base closure for this analysis, sufficient documentation was available from 2422 eligible pts. Results: The proportion of pts receiving T without preceding or concomitant CT (noCT) was 180/2422 (7.4%). This subgroup was characterized by higher age (median 58 vs.56 in the CT group, p=0.0026; ≥70 years: 18%/10%), smaller primaries (pT1 49%/43%, p=0.11), more favorable grading (G3 45%/53%, p=0.045), a higher proportion of positive hormone receptor (67%/61%, p=0.096) and less radiotherapy (64%/79%, p<0.0001). The strong association to radiotherapy is probably due to the fact, that the choice of this additional modality reflects the overall risk assessment of the pt. In contrast, there was no difference in nodal involvement (pN0: 52%/51%; positive nodes: mean 2.5/2.4). In multivariate analysis (logistic regression model, not incorporating radiotherapy), hormone receptor status is not predictive (p=0.41), while age ≥65 (p=0.0011), grade 1/2 (p=0.046) and pT1 (p=0.089) independently remain at least borderline significant. The mean number of T administrations was 18 and the median duration of T therapy was 12 months in the noCT group as well as the CT group. 57% of the noCT pts received adjuvant endocrine therapy. In the CT group, 81% received anthracyclines and 61% taxanes. Based on a still low number of only 13 observed events in the noCT group, no differences in relapse-free survival could be detected (p=0.38). Pathological cardiac findings in the pt's history was not predictive of therapy selection (6%/7%) and were also similarly distributed at the end of T therapy (7%/8%). Cardiac function disorders of CTC grade 3/4 were reported in 1% of both groups, across all grades slightly less frequent in the noCT group (2.8%/4.0%). Conclusions: A small, but distinct group of early BC pts without adjuvant chemotherapy receives T treatment for HER2+ disease. These patients are characterized by higher age and favorable primary tumor staging and grading, but not by cardiac comorbidities. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-21.

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