Trastuzumab Plus Chemotherapy: Convincing Survival Benefit or Not?

Abstract

Trastuzumab has altered the lives of many women with Her-2/neu-amplified metastatic breast cancer (MBC). Within our clinical practice, we have several women who continue receiving trastuzumab 5 to 9 years after the initiation of therapy. Long survival durations in MBC are not uncommon for patients with hormonally sensitive tumors, but for Her-2/neu-amplified tumors the prognosis was dismal before the use of this agent. 1 Improvements in survival from first relapse with MBC have occurred during the last decades 2,3 secondary to the development of new hormonal and cytotoxic agents. Despite these gradual improvements in survival from first relapse, there are few trials demonstrating convincing benefits in overall survival for a novel regimen compared with a more standard comparator. The article by Marty et al 4 in this issue of the Journal of Clinical Oncology confirms an overall survival benefit produced by a trastuzumab plus chemotherapy combination over chemotherapy alone. The survival benefit for a combination of trastuzumab plus chemotherapy was originally described by Slamon et al 5 in one of the pivotal clinical trials of trastuzumab.In the trial by Marty et al, 4 weekly trastuzumab plus docetaxel 100 mg/m 2 every 3 weeks proved superior to the same dose of single-agent docetaxel in all end points including response rate, response duration, time to progression, treatment failure, and most importantly, overall survival (31.2 v 22.7 months; P ϭ .0062). In the pivotal trial, 5 there was also a statistically significant survival benefit when patients treated with chemotherapy plus trastuzumab (n ϭ 235) were compared with those treated with chemotherapy alone (n ϭ 234; 25.1 v 20.3 months; P ϭ .046). In that trial, women with no prior anthracycline adjuvant therapy received an anthracycline plus cyclophosphamide (AC) alone or in combination with trastuzumab. Women with prior anthracycline adjuvant therapy were randomly assigned to paclitaxel 175 mg/m 2 every 3 weeks alone or with trastuzumab. The overall survival advantage for AC ϩ trastuzumab over AC alone was 26.8% v 21.4% (P ϭ .16). An unexpected high cardiotoxicity rate led to the recommendation to avoid concomitant anthracycline use with trastuzumab outside of clinical trials. These recommendations are being challenged by provocative trials, such as the neoadjuvant trial by Buzdar, 6 in which paclitaxel followed by an epirubicin-containing regimen was administered with concurrent trastuzumab, resulting in a 65% pathologic complete response rate with no cardiotoxicity. Other trials are re-exploring anthracyclines plus trastuzumab, also with encouraging efficacy results and a relative lack of cardiotoxicity. Examples include the liposomal doxorubicins 7-10 and epirubicin. 11 However, such combinations should still be limited to clinical trials.Although the anthracycline plus trastuzumab clinical trials cited above are of interest for future development, data by Marty et al 4 are more relevant to current practice, given that taxane plus trastuzumab combinations a...

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Phase II Trial of Weekly Nanoparticle Albumin-Bound Paclitaxel With Carboplatin and Trastuzumab as First-line Therapy for Women With HER2-Overexpressing Metastatic Breast Cancer

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Serum Tumor Markers in Breast Cancer: Are They of Clinical Value?

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