Trastuzumab associated with successive cytotoxic therapies beyond disease progression in metastatic breast cancer

Abstract

10617 Background: Whether trastuzumab should be continued after tumor progression remains unknown.We describe the activity of successive trastuzumab-containing regimens in patients with HER2-overexpressing metastatic breast cancer, as well as the response rate, time to progression and predictive factors for response. Methods: Descriptive retrospective study of trastuzumab activity in patients with HER2-overexpressing metastatic breast cancer treated at our hospital from 10/1999 to 07/2005. Results: 93 consecutive patients were evaluated obtaining an objective response rate (OR) for first-time administration of trastuzumab of 46.2%; stable disease (SD) 24.7%; clinical benefit (CB) 71%. Median time-to-progression (TTP) was 5 months (range: 1–39+). A total of 47 pts (50.5%) received a second trastuzumab-containing regimen with an OR of 29.8%; SD 21.3%; CB 51.1%; TTP 4 months (range: 1–31). A total of 21 pts (22.6%) received a third trastuzumab-containing regimen; OR 38.1%; SD 23.8%; CB 61.9%; TTP 4 months (range: 1–30+). A total of 10 pts (10.8%) received a fourth trastuzumab-containing regimen; OR 20%; SD 20%; CB 40%; TTP 4 months (range: 1–37). 5 pts (5.4%) received a fifth trastuzumab-containing regimen; OR 0%; SD 60%. Age < 45 years is a significant prognostic factor (p: 0.005, 95% CI, OR 5.6 (1.5–20.6)). A better response rate in the successive trastuzumab-containing regimens was observed, when there was a response in the first regimen: p = 0.04; 95% CI; OR 3.84 (1.07–14.65). With a follow-up of 16,5 months 45 pts (48,4%) are alive. Conclusions: Trastuzumab-containing therapies beyond disease progression in metastatic breast cancer show activity. There were more responses in younger pts. Those pts who had a previous response to trastuzumab therapy were more likely to respond to successive trastuzumab-containing regimens. Additional controlled studies are needed to test this approach. No significant financial relationships to disclose.

Continuing trastuzumab beyond disease progression: outcomes analysis in patients with metastatic breast cancer

“…Various authors have carried out similar analyses showing heterogeneous results. As far as response rate is concerned, many authors reported results that are analogous to ours [ 14 , 17 , 19 , 20 ], but in two studies [ 18 , 21 ] response rates have appeared very similar for first- and second-line trastuzumab-based treatments (Table 3 ), thus supporting the hypothesis of a potentiation of further chemotherapy regimens by retaining trastuzumab after progression. When TTP is analyzed, studies have again shown inconsistent results (Table 3 ).…”

“…A similar TTP degradation is reported by Montemurro and colleagues [ 20 ] (median TTP: 9.0 versus 6.3 months, first versus second line, respectively) and by Metro and colleagues [ 19 ] (median TTP: 9.5 versus 6.7 months, first versus second line, respectively). Conversely, in the Spanish and Austrian studies [ 14 , 17 ], TTP is approximately constant between the first and second lines, whereas in the global retrospective analysis by Gelmon and colleagues [ 18 ], the TTP of the second trastuzumab regimen is even longer than the first one (26 versus 23.5 weeks, respectively). At analytical examination, we were unable to identify distinguishing characteristics of these studies which may explain such different results.…”

Trastuzumab in combination with metronomic cyclophosphamide and methotrexate in patients with HER-2 positive metastatic breast cancer

“…The opportunity, in patients with progressive disease, of continuing trastuzumab combined with a non cross resistant chemotherapeutic regimen is a crucial question regarding trastuzumab strategy. Data on restored efficacy of trastuzumab with further associations after failure are limited, although some activity was recently reported in patients with progressive disease during trastuzumab therapy regarding a further non cross resistant chemotherapeutic regimen in combination with trastuzumab [ 20 - 22 ].…”

Randomized Phase II Study Comparing Efficacy and Safety of Combination-Therapy Trastuzumab and Docetaxel vs. Sequential Therapy of Trastuzumab Followed by Docetaxel Alone at Progression As First-Line Chemotherapy in Patients with HER2+ Metastatic Breast Cancer: HERTAX Trial

“…Other retrospectively collected data are not consistent on the value of trastuzumab treatment beyond progression, although in the majority of reports a benefit is suggested. [18][19][20][21][22][23][24] One of the limitations of our study, related to the phase II character, is the relatively small sample size, hindering a definite conclusion with regard to OS. Furthermore, it would have been interesting if on finishing protocol treatment, patients were enrolled in a subsequent randomized study evaluating the continu-ation of trastuzumab beyond progression.…”