Phase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in HER2-positive metastatic breast cancer.
Breast Cancer Res
; 18(1): 34, 2016 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-26979312
ABSTRACT
BACKGROUND:
In pre-clinical studies, the anti-tumor activity of T-DM1 was enhanced when combined with taxanes or pertuzumab. This phase 1b/2a study evaluated the safety/tolerability of T-DM1 + paclitaxel ± pertuzumab in HER2-positive advanced breast cancer.METHODS:
In phase 1b (n = 60), a 3 + 3 dose-escalation approach was used to determine the maximum tolerated dose (MTD) of T-DM1 + paclitaxel ± pertuzumab. The primary objective of phase 2a was feasibility, with 44 patients randomized to T-DM1 + paclitaxel ± pertuzumab at the MTD identified in phase 1b.RESULTS:
The MTD was T-DM1 3.6 mg/kg every three weeks (q3w) or 2.4 mg/kg weekly + paclitaxel 80 mg/m(2) weekly ± pertuzumab 840 mg loading dose followed by 420 mg q3w. Phase 2a patients had received a median of 5.0 (range 0-10) prior therapies for advanced cancer. In phase 2a, 51.2 % received ≥12 paclitaxel doses within 15 weeks, and 14.0 % received 12 paclitaxel doses by week 12. Common all-grade adverse events (AEs) were peripheral neuropathy (90.9 %) and fatigue (79.5 %). A total of 77.3 % experienced grade ≥3 AEs, most commonly neutropenia (25.0 %) and peripheral neuropathy (18.2 %). Among the 42 phase 2a patients with measurable disease, the objective response rate (ORR) was 50.0 % (95 % confidence interval (CI) 34.6-65.4); the clinical benefit rate (CBR) was 56.8 % (95 % CI 41.6-71.0). No pharmacokinetic interactions were observed between T-DM1 and paclitaxel.CONCLUSIONS:
This regimen showed clinical activity. Although there is potential for paclitaxel to be added to T-DM1 ± pertuzumab, peripheral neuropathy was common in this heavily pretreated population. TRIAL REGISTRATION ClinicalTrials.gov NCT00951665 . Registered August 3, 2009.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Paclitaxel
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Anticorpos Monoclonais Humanizados
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Maitansina
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article