Do HER-2 positive metastatic breast cancer patients benefit from the use of trastuzumab beyond disease progression? A mono-institutional experience and systematic review of observational studies

Abstract

Though preclinical evidence supports the protracted use of trastuzumab to reach sustained anti-tumor activity, the activity of trastuzumab beyond disease progression remains controversial in HER-2 over-expressing (HER-2+) metastatic breast cancer (MBC) patients. We retrospectively evaluated a total of 59 patients with HER-2 + MBC treated at our institution with trastuzumab-based therapies. Our results were added to those obtained in similar observational studies and summary estimates for overall response (OR) and clinical benefit (CB) to first and second trastuzumab-based lines were calculated. In our series of patients we observed an OR of 59.3% and 27% for first and second trastuzumab-based lines, respectively, with a corresponding CB of 83% and 62.2%, respectively. Time to first and second progression were 9.5 months and 6.7 months, respectively. The combined analysis showed an OR of 50% for first trastuzumab-based regimen and 21.2% for second trastuzumab-based line. The corresponding values for CB were 77.6% and 42.6%, respectively. A second trastuzumab-containing regimen beyond progression yields a considerable rate of OR and CB in HER-2 + MBC patients. Randomized trials are warranted.

Increased overall survival independent of RECIST response in metastatic breast cancer patients continuing trastuzumab treatment: evidence from a retrospective study

“…While a number of retrospective analyses have shown a potential advantage for the "continuation policy" (reviewed in [3][4][5][6]) in agreement with our results, two retrospective studies indicated no statistically significant benefit from continuing trastuzumab [17,6]. In these studies, carried out by the same group, the authors themselves suggest that patients continuing trastuzumab might have been subject to closer clinical evaluation because of the weekly administration schedule of the antibody compared to the control arm of untreated patients, and an earlier detection of disease progression may have partially clouded the benefit of continuation.…”

“…However, patients may develop resistance to trastuzumab and show metastatic disease progression. Several retrospective studies published thus far (reviewed in [3,4]) [5,6] have indicated a certain overall response rate, clinical benefit and extended time to progression from the use of a second trastuzumabcontaining regimen in HER2-positive MBC patients who progressed on first-line trastuzumab treatment. Moreover, two recent randomized trials designed to directly evaluate the efficacy of continuing trastuzumab after progression demonstrated the potential clinical utility of continuing trastuzumab even for patients with progressive disease [7,8].…”

Prolonged complete remission of metastatic HER2-positive breast cancer after continuous trastuzumab treatment: a case report and review of the literature

“…This experience confirms other analysis with patients who received second-line trastuzumab-based chemotherapy for metastatic disease. They achieved a median OS significantly better than those discontinuing trastuzumab at disease progression [14][15][16][17]13] The long term use of trastuzumab raises concerns about cardiotoxicity. An early pivotal trial showed a high incidence of cardiac events under the treatment of trastuzumab, especially when associated with anthracyclines [8].…”

Lapatinib in patients with metastatic breast cancer following initial treatment with trastuzumab: an economic analysis from the Brazilian public health care perspective

“…Although not currently approved by the Brazilian National Agency of Health Surveillance (ANVISA) for use after disease progression is observed, observational data support clinical benefits with TRAST/CAP continuation. 13 Another treatment option currently includes lapatinib combined with capecitabine (LAP/CAP), which is also supported by clinical evidence. 14 In addition, LAP/CAP is approved for use in Brazil in patients with MBC following initial treatment with TRAST/CAP.…”