Phase I study of alpelisib (BYL-719) and trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer (MBC) after trastuzumab and taxane therapy

Phase I study of alpelisib (BYL-719) and trastuzumab emtansine (T-DM1) in HER2-positive... Purpose Activation of the phosphoinositide 3-kinase (PI3K) pathway is an important resistance mechanism to anti-HER2 therapies. This study aimed to assess the safety and activity of alpelisib (a PI3Kα isoform-specific inhibitor) with T-DM1 in trastuzumab- and taxane-resistant HER2-positive MBC. Methods Patients with HER2-positive MBC that had progressed on trastuzumab-based therapy were treated with alpelisib daily and T-DM1 3.6 mg/kg every 3 weeks. The dose-limiting toxicity (DLT), maximum tolerated dose (MTD), adverse events, overall response rate (ORR), and clinical benefit rate (CBR = CR + PR + SD > 6 months) were assessed with descrip- tive statistics. Progression-free survival (PFS) was calculated by the Kaplan–Meier method. Results Seventeen patients were enrolled with a median of 3 prior therapies for metastatic disease. The DLT was a macu- lopapular rash and MTD was 250 mg alpelisib daily. The most frequently occurring toxicities included fatigue, rash, gas- trointestinal side effects, thrombocytopenia, anemia, elevated liver enzymes, and hyperglycemia. Fourteen patients were evaluable for response with an ORR of 43%. In patients with prior treatment and progression on T-DM1 (n = 10), the ORR was 30%. The CBR was 71% in evaluable patients and 60% in those with prior T-DM1. The median PFS was 8.1 months. Conclusions http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Breast Cancer Research and Treatment Springer Journals

Phase I study of alpelisib (BYL-719) and trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer (MBC) after trastuzumab and taxane therapy

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Publisher
Springer US
Copyright
Copyright © 2018 by Springer Science+Business Media, LLC, part of Springer Nature
Subject
Medicine & Public Health; Oncology
ISSN
0167-6806
eISSN
1573-7217
D.O.I.
10.1007/s10549-018-4792-0
Publisher site
See Article on Publisher Site

Abstract

Purpose Activation of the phosphoinositide 3-kinase (PI3K) pathway is an important resistance mechanism to anti-HER2 therapies. This study aimed to assess the safety and activity of alpelisib (a PI3Kα isoform-specific inhibitor) with T-DM1 in trastuzumab- and taxane-resistant HER2-positive MBC. Methods Patients with HER2-positive MBC that had progressed on trastuzumab-based therapy were treated with alpelisib daily and T-DM1 3.6 mg/kg every 3 weeks. The dose-limiting toxicity (DLT), maximum tolerated dose (MTD), adverse events, overall response rate (ORR), and clinical benefit rate (CBR = CR + PR + SD > 6 months) were assessed with descrip- tive statistics. Progression-free survival (PFS) was calculated by the Kaplan–Meier method. Results Seventeen patients were enrolled with a median of 3 prior therapies for metastatic disease. The DLT was a macu- lopapular rash and MTD was 250 mg alpelisib daily. The most frequently occurring toxicities included fatigue, rash, gas- trointestinal side effects, thrombocytopenia, anemia, elevated liver enzymes, and hyperglycemia. Fourteen patients were evaluable for response with an ORR of 43%. In patients with prior treatment and progression on T-DM1 (n = 10), the ORR was 30%. The CBR was 71% in evaluable patients and 60% in those with prior T-DM1. The median PFS was 8.1 months. Conclusions

Journal

Breast Cancer Research and TreatmentSpringer Journals

Published: May 30, 2018

References

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