T-DM1 Activity in Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancers That Received Prior Therapy With Trastuzumab and Pertuzumab.
Purpose Ado-trastuzumab emtansine (T-DM1) is currently approved for treatment in patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (MBC) who previously received trastuzumab and a taxane. However, there are no data on the activity of T-DM1 in patients who received prior pertuzumab, which is now included as standard first-line therapy. The goal of this study was to assess the efficacy of T-DM1 in routine clinical practice in a contemporary patient population that received both prior trastuzumab and pertuzumab. Patients and Methods We identified all patients with HER2-positive MBC who received T-DM1 after trastuzumab and pertuzumab between March 1, 2013, and July 15, 2015, via electronic pharmacy records and departmental databases at three institutions: MD Anderson Cancer Center, Smilow Cancer Hospital at Yale, and The James Cancer Hospital at the Ohio State University. We reviewed medical records of each case to confirm treatment sequencing and outcome. Results Of patients, 82 were identified and 78 were available for outcome analysis; 32% received T-DM1 as first- and second-line line therapy, and 48% received it as fourth-line treatment or later. Rate of prolonged duration on therapy, defined as duration on therapy ≥ 6 months, was 30.8% (95% CI, 20.6% to 41.1%), and tumor response rate was 17.9% (95% CI, 9.4% to 26.4%). Median duration on therapy was 4.0 months (95% CI, 2.7 to 5.1; range, 0 to 22.5 months). T-DM1 was discontinued for disease progression in 84% of patients and for toxicity in 10%. Conclusion Tumor response rates were lower than in prior reports of trastuzumab-resistant, HER2-positive MBC, but one third of patients received therapy with T-DM1 for ≥ 6 months, which suggests a clinically relevant benefit in patients who received prior pertuzumab.
Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.
Hannah
H
Dzimitrowicz
Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.
Michael
M
Berger
Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.
Craig
C
Vargo
Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.
Annette
A
Hood
Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.
Osama
O
Abdelghany
Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.
Akshara Singareeka
AS
Raghavendra
Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.
Debu
D
Tripathy
Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.
Vicente
V
Valero
Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.
Christos
C
Hatzis
Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.
Lajos
L
Pusztai
Hannah Dzimitrowicz, Annette Hood, Osama Abdelghany, Christos Hatzis, and Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Michael Berger and Craig Vargo, The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH; and Akshara Singareeka Raghavendra, Debu Tripathy, Vicente Valero, and Rashmi Murthy, MD Anderson Cancer Center, Houston, TX.
Rashmi
R
Murthy
D000080044:Ado-Trastuzumab Emtansine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D008453:Maytansine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D066066:Response Evaluation Criteria in Solid Tumors; D019233:Retreatment; D012189:Retrospective Studies; D000068878:Trastuzumab / Q000627:therapeutic use
D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008453:Maytansine; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C485206:pertuzumab