Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study.
Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study.
- 2022
Available online from MWHC library: 1999 - present, Available in print through MWHC library: 1999 - 2008
CONCLUSION: The primary end point was not met. Both arms achieved favorable IDFS. Trastuzumab plus pertuzumab plus chemotherapy remains the standard of care for high-risk HER2-positive EBC. METHODS: The phase III KAITLIN study (NCT01966471) included adults with excised HER2-positive EBC (node-positive or node-negative, hormone receptor-negative, and tumor > 2.0 cm). Postsurgery, patients were randomly assigned 1:1 to anthracycline-based chemotherapy (three-four cycles) and then 18 cycles of T-DM1 plus pertuzumab (AC-KP) or taxane (three-four cycles) plus trastuzumab plus pertuzumab (AC-THP). Adjuvant radiotherapy/endocrine therapy was permitted. Coprimary end points were invasive disease-free survival (IDFS) in the intention-to-treat node-positive and overall populations with hierarchical testing. PURPOSE: We aimed to improve efficacy and reduce toxicity of high-risk human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) treatment by replacing taxanes and trastuzumab with trastuzumab emtansine (T-DM1). RESULTS: The median follow-up was 57.1 months (interquartile range 52.1-60.1 months) for AC-THP (n = 918) and 57.0 months (interquartile range 52.1-59.8 months) for AC-KP (n = 928). There was no significant IDFS difference between arms in the node-positive (n = 1,658; stratified hazard ratio [HR], 0.97; 95% CI, 0.71 to 1.32) or overall population (n = 1846; stratified HR, 0.98; 95% CI, 0.72 to 1.32). In the overall population, the three-year IDFS was 94.2% (95% CI, 92.7 to 95.8) for AC-THP and 93.1% (95% CI, 91.4 to 94.7) for AC-KP. Treatment completion rates (ie, 18 cycles) were 88.4% for AC-THP and 65.0% for AC-KP (difference driven by T-DM1 discontinuation because of laboratory abnormalities [12.5%]). Similar rates of grade >= 3 (55.4% v 51.8%) and serious adverse events (23.3% v 21.4%) occurred with AC-THP and AC-KP, respectively. KP decreased clinically meaningful deterioration in global health status versus THP (stratified HR, 0.71; 95% CI, 0.62 to 0.80).
English
0732-183X
10.1200/JCO.21.00896 [doi]
*Ado-Trastuzumab Emtansine/tu [Therapeutic Use]
*Anthracyclines/tu [Therapeutic Use]
*Antibiotics, Antineoplastic/tu [Therapeutic Use]
*Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
*Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
*Breast Neoplasms/dt [Drug Therapy]
*Receptor, ErbB-2/ai [Antagonists & Inhibitors]
*Trastuzumab/tu [Therapeutic Use]
Ado-Trastuzumab Emtansine/ae [Adverse Effects]
Adult
Aged
Anthracyclines/ae [Adverse Effects]
Antibiotics, Antineoplastic/ae [Adverse Effects]
Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
Breast Neoplasms/en [Enzymology]
Breast Neoplasms/pa [Pathology]
Chemotherapy, Adjuvant
Disease-Free Survival
Female
Humans
Middle Aged
Receptor, ErbB-2/me [Metabolism]
Time Factors
Trastuzumab/ae [Adverse Effects]
Associate Dean for Research Development
Journal Article
Available online from MWHC library: 1999 - present, Available in print through MWHC library: 1999 - 2008
CONCLUSION: The primary end point was not met. Both arms achieved favorable IDFS. Trastuzumab plus pertuzumab plus chemotherapy remains the standard of care for high-risk HER2-positive EBC. METHODS: The phase III KAITLIN study (NCT01966471) included adults with excised HER2-positive EBC (node-positive or node-negative, hormone receptor-negative, and tumor > 2.0 cm). Postsurgery, patients were randomly assigned 1:1 to anthracycline-based chemotherapy (three-four cycles) and then 18 cycles of T-DM1 plus pertuzumab (AC-KP) or taxane (three-four cycles) plus trastuzumab plus pertuzumab (AC-THP). Adjuvant radiotherapy/endocrine therapy was permitted. Coprimary end points were invasive disease-free survival (IDFS) in the intention-to-treat node-positive and overall populations with hierarchical testing. PURPOSE: We aimed to improve efficacy and reduce toxicity of high-risk human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) treatment by replacing taxanes and trastuzumab with trastuzumab emtansine (T-DM1). RESULTS: The median follow-up was 57.1 months (interquartile range 52.1-60.1 months) for AC-THP (n = 918) and 57.0 months (interquartile range 52.1-59.8 months) for AC-KP (n = 928). There was no significant IDFS difference between arms in the node-positive (n = 1,658; stratified hazard ratio [HR], 0.97; 95% CI, 0.71 to 1.32) or overall population (n = 1846; stratified HR, 0.98; 95% CI, 0.72 to 1.32). In the overall population, the three-year IDFS was 94.2% (95% CI, 92.7 to 95.8) for AC-THP and 93.1% (95% CI, 91.4 to 94.7) for AC-KP. Treatment completion rates (ie, 18 cycles) were 88.4% for AC-THP and 65.0% for AC-KP (difference driven by T-DM1 discontinuation because of laboratory abnormalities [12.5%]). Similar rates of grade >= 3 (55.4% v 51.8%) and serious adverse events (23.3% v 21.4%) occurred with AC-THP and AC-KP, respectively. KP decreased clinically meaningful deterioration in global health status versus THP (stratified HR, 0.71; 95% CI, 0.62 to 0.80).
English
0732-183X
10.1200/JCO.21.00896 [doi]
*Ado-Trastuzumab Emtansine/tu [Therapeutic Use]
*Anthracyclines/tu [Therapeutic Use]
*Antibiotics, Antineoplastic/tu [Therapeutic Use]
*Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
*Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
*Breast Neoplasms/dt [Drug Therapy]
*Receptor, ErbB-2/ai [Antagonists & Inhibitors]
*Trastuzumab/tu [Therapeutic Use]
Ado-Trastuzumab Emtansine/ae [Adverse Effects]
Adult
Aged
Anthracyclines/ae [Adverse Effects]
Antibiotics, Antineoplastic/ae [Adverse Effects]
Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
Breast Neoplasms/en [Enzymology]
Breast Neoplasms/pa [Pathology]
Chemotherapy, Adjuvant
Disease-Free Survival
Female
Humans
Middle Aged
Receptor, ErbB-2/me [Metabolism]
Time Factors
Trastuzumab/ae [Adverse Effects]
Associate Dean for Research Development
Journal Article