PMID- 26979312
OWN - NLM
STAT- MEDLINE
DCOM- 20161007
LR  - 20220310
IS  - 1465-542X (Electronic)
IS  - 1465-5411 (Print)
IS  - 1465-5411 (Linking)
VI  - 18
IP  - 1
DP  - 2016 Mar 15
TI  - Phase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in 
      HER2-positive metastatic breast cancer.
PG  - 34
LID - 10.1186/s13058-016-0691-7 [doi]
LID - 34
AB  - 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.
FAU - Krop, Ian E
AU  - Krop IE
AD  - Breast Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 
      02215, USA. Ian_Krop@dfci.harvard.edu.
FAU - Modi, Shanu
AU  - Modi S
AD  - Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, 
      USA.
AD  - Weill Cornell Medical College, 445 E 69th St, New York, NY, 10021, USA.
FAU - LoRusso, Patricia M
AU  - LoRusso PM
AD  - Yale University, 800 Howard Ave, New Haven, CT, 06519, USA.
FAU - Pegram, Mark
AU  - Pegram M
AD  - Stanford Cancer Institute, Stanford University School of Medicine, 900 Blake 
      Wilbur, Stanford, CA, 94305, USA.
FAU - Guardino, Ellie
AU  - Guardino E
AD  - Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
FAU - Althaus, Betsy
AU  - Althaus B
AD  - Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
FAU - Lu, Dan
AU  - Lu D
AD  - Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
FAU - Strasak, Alexander
AU  - Strasak A
AD  - F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, Basel, ch-4070, Switzerland.
FAU - Elias, Anthony
AU  - Elias A
AD  - University of Colorado Cancer Center, 1665 Aurora Ct, Aurora, CO, 80045, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00951665
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20160315
PL  - England
TA  - Breast Cancer Res
JT  - Breast cancer research : BCR
JID - 100927353
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 14083FR882 (Maytansine)
RN  - K16AIQ8CTM (pertuzumab)
RN  - P188ANX8CK (Trastuzumab)
RN  - P88XT4IS4D (Paclitaxel)
RN  - SE2KH7T06F (Ado-Trastuzumab Emtansine)
SB  - IM
MH  - Ado-Trastuzumab Emtansine
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects
MH  - Breast Neoplasms/*drug therapy/pathology
MH  - Female
MH  - Humans
MH  - Maximum Tolerated Dose
MH  - Maytansine/administration & dosage/adverse effects/*analogs & derivatives
MH  - Middle Aged
MH  - Paclitaxel/*administration & dosage/adverse effects
MH  - Trastuzumab
PMC - PMC4791863
EDAT- 2016/03/17 06:00
MHDA- 2016/10/08 06:00
PMCR- 2016/03/15
CRDT- 2016/03/17 06:00
PHST- 2015/12/18 00:00 [received]
PHST- 2016/02/26 00:00 [accepted]
PHST- 2016/03/17 06:00 [entrez]
PHST- 2016/03/17 06:00 [pubmed]
PHST- 2016/10/08 06:00 [medline]
PHST- 2016/03/15 00:00 [pmc-release]
AID - 10.1186/s13058-016-0691-7 [pii]
AID - 691 [pii]
AID - 10.1186/s13058-016-0691-7 [doi]
PST - epublish
SO  - Breast Cancer Res. 2016 Mar 15;18(1):34. doi: 10.1186/s13058-016-0691-7.