A Phase I/II study of the combination of lapatinib and oral vinorelbine in HER2-positive metastatic breast cancer

Tom Wei-Wu Chen, Dah-Cherng Yeh, Tsu-Yi Chao, Ching-Hung Lin, Louis Wing-Cheong Chow, Dwan-Ying Chang, Yao-Yu Hsieh, Shu-Min Huang, Ann-Lii Cheng, Yen-Shen Lu

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Abstract

Background: The combination of lapatinib and oral vinorelbine for HER2 positive metastatic breast cancer (MBC) is convenient but with uncertain toxicity profiles. A Phase I/II study was designed to understand the tolerability and efficacy of this combination treatment.

Method: Female MBC patients with HER2 positive were eligible. Lapatinib was given once daily and oral vinorelbine was given on Days 1 and 8 of a 21-day cycle. A 3 + 3 standard dose-escalation rule was applied in the Phase I study. The primary endpoint of the Phase II study was PFS. In the Phase II part, because no DLT was observed in the first 20 patients, vinorelbine dose-escalation was permitted if no significant toxicities after the first cycle was observed.

Result: From June 2009 to February 2013, 46 patients were enrolled in Phase I (n = 15) and II (n = 31) studies. Median age was 52.8 (range 34.3-84.0); 28 (60.9%) patients were ER positive. In the Phase I study, two patients had DLTs (neutropenia (n = 2), diarrhea (n = 1)). The MTD was determined at lapatinib 1000 mg plus oral vinorelbine 50 mg/m2. In the Phase II study, 11 patients safely had vinorelbine escalated to 60 mg/m2 on cycle 2. The median PFS was 5.6 months (95% CI 5.2-5.9); 6 (19.4%) patients had PR; the clinical benefit rate was 38.7%. Six patients had disease control over 2 years.

Conclusion: Lapatinib 1000 mg and oral vinorelbine 50 mg/m2 were tolerable with manageable toxicities. Escalation to vinorelbine 60 mg/m2 is feasible if no significant toxicities after the first cycle. Clinical efficacy was demonstrated with long-term responders observed.

Original languageEnglish
Pages (from-to)242-247
Number of pages6
JournalJapanese Journal of Clinical Oncology
Volume48
Issue number3
DOIs
Publication statusPublished - Mar 1 2018

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Breast Neoplasms
lapatinib
vinorelbine
Neutropenia
Diarrhea

Keywords

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols/adverse effects
  • Breast Neoplasms/drug therapy
  • Demography
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Lapatinib
  • Middle Aged
  • Neoplasm Metastasis
  • Quinazolines/adverse effects
  • Receptor, ErbB-2/metabolism
  • Treatment Outcome
  • Vinblastine/administration & dosage
  • Vinorelbine

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A Phase I/II study of the combination of lapatinib and oral vinorelbine in HER2-positive metastatic breast cancer. / Chen, Tom Wei-Wu; Yeh, Dah-Cherng; Chao, Tsu-Yi; Lin, Ching-Hung; Chow, Louis Wing-Cheong; Chang, Dwan-Ying; Hsieh, Yao-Yu; Huang, Shu-Min; Cheng, Ann-Lii; Lu, Yen-Shen.

In: Japanese Journal of Clinical Oncology, Vol. 48, No. 3, 01.03.2018, p. 242-247.

Research output: Contribution to journalArticle

Chen, Tom Wei-Wu ; Yeh, Dah-Cherng ; Chao, Tsu-Yi ; Lin, Ching-Hung ; Chow, Louis Wing-Cheong ; Chang, Dwan-Ying ; Hsieh, Yao-Yu ; Huang, Shu-Min ; Cheng, Ann-Lii ; Lu, Yen-Shen. / A Phase I/II study of the combination of lapatinib and oral vinorelbine in HER2-positive metastatic breast cancer. In: Japanese Journal of Clinical Oncology. 2018 ; Vol. 48, No. 3. pp. 242-247.
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abstract = "Background: The combination of lapatinib and oral vinorelbine for HER2 positive metastatic breast cancer (MBC) is convenient but with uncertain toxicity profiles. A Phase I/II study was designed to understand the tolerability and efficacy of this combination treatment.Method: Female MBC patients with HER2 positive were eligible. Lapatinib was given once daily and oral vinorelbine was given on Days 1 and 8 of a 21-day cycle. A 3 + 3 standard dose-escalation rule was applied in the Phase I study. The primary endpoint of the Phase II study was PFS. In the Phase II part, because no DLT was observed in the first 20 patients, vinorelbine dose-escalation was permitted if no significant toxicities after the first cycle was observed.Result: From June 2009 to February 2013, 46 patients were enrolled in Phase I (n = 15) and II (n = 31) studies. Median age was 52.8 (range 34.3-84.0); 28 (60.9{\%}) patients were ER positive. In the Phase I study, two patients had DLTs (neutropenia (n = 2), diarrhea (n = 1)). The MTD was determined at lapatinib 1000 mg plus oral vinorelbine 50 mg/m2. In the Phase II study, 11 patients safely had vinorelbine escalated to 60 mg/m2 on cycle 2. The median PFS was 5.6 months (95{\%} CI 5.2-5.9); 6 (19.4{\%}) patients had PR; the clinical benefit rate was 38.7{\%}. Six patients had disease control over 2 years.Conclusion: Lapatinib 1000 mg and oral vinorelbine 50 mg/m2 were tolerable with manageable toxicities. Escalation to vinorelbine 60 mg/m2 is feasible if no significant toxicities after the first cycle. Clinical efficacy was demonstrated with long-term responders observed.",
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T1 - A Phase I/II study of the combination of lapatinib and oral vinorelbine in HER2-positive metastatic breast cancer

AU - Chen, Tom Wei-Wu

AU - Yeh, Dah-Cherng

AU - Chao, Tsu-Yi

AU - Lin, Ching-Hung

AU - Chow, Louis Wing-Cheong

AU - Chang, Dwan-Ying

AU - Hsieh, Yao-Yu

AU - Huang, Shu-Min

AU - Cheng, Ann-Lii

AU - Lu, Yen-Shen

N1 - © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Background: The combination of lapatinib and oral vinorelbine for HER2 positive metastatic breast cancer (MBC) is convenient but with uncertain toxicity profiles. A Phase I/II study was designed to understand the tolerability and efficacy of this combination treatment.Method: Female MBC patients with HER2 positive were eligible. Lapatinib was given once daily and oral vinorelbine was given on Days 1 and 8 of a 21-day cycle. A 3 + 3 standard dose-escalation rule was applied in the Phase I study. The primary endpoint of the Phase II study was PFS. In the Phase II part, because no DLT was observed in the first 20 patients, vinorelbine dose-escalation was permitted if no significant toxicities after the first cycle was observed.Result: From June 2009 to February 2013, 46 patients were enrolled in Phase I (n = 15) and II (n = 31) studies. Median age was 52.8 (range 34.3-84.0); 28 (60.9%) patients were ER positive. In the Phase I study, two patients had DLTs (neutropenia (n = 2), diarrhea (n = 1)). The MTD was determined at lapatinib 1000 mg plus oral vinorelbine 50 mg/m2. In the Phase II study, 11 patients safely had vinorelbine escalated to 60 mg/m2 on cycle 2. The median PFS was 5.6 months (95% CI 5.2-5.9); 6 (19.4%) patients had PR; the clinical benefit rate was 38.7%. Six patients had disease control over 2 years.Conclusion: Lapatinib 1000 mg and oral vinorelbine 50 mg/m2 were tolerable with manageable toxicities. Escalation to vinorelbine 60 mg/m2 is feasible if no significant toxicities after the first cycle. Clinical efficacy was demonstrated with long-term responders observed.

AB - Background: The combination of lapatinib and oral vinorelbine for HER2 positive metastatic breast cancer (MBC) is convenient but with uncertain toxicity profiles. A Phase I/II study was designed to understand the tolerability and efficacy of this combination treatment.Method: Female MBC patients with HER2 positive were eligible. Lapatinib was given once daily and oral vinorelbine was given on Days 1 and 8 of a 21-day cycle. A 3 + 3 standard dose-escalation rule was applied in the Phase I study. The primary endpoint of the Phase II study was PFS. In the Phase II part, because no DLT was observed in the first 20 patients, vinorelbine dose-escalation was permitted if no significant toxicities after the first cycle was observed.Result: From June 2009 to February 2013, 46 patients were enrolled in Phase I (n = 15) and II (n = 31) studies. Median age was 52.8 (range 34.3-84.0); 28 (60.9%) patients were ER positive. In the Phase I study, two patients had DLTs (neutropenia (n = 2), diarrhea (n = 1)). The MTD was determined at lapatinib 1000 mg plus oral vinorelbine 50 mg/m2. In the Phase II study, 11 patients safely had vinorelbine escalated to 60 mg/m2 on cycle 2. The median PFS was 5.6 months (95% CI 5.2-5.9); 6 (19.4%) patients had PR; the clinical benefit rate was 38.7%. Six patients had disease control over 2 years.Conclusion: Lapatinib 1000 mg and oral vinorelbine 50 mg/m2 were tolerable with manageable toxicities. Escalation to vinorelbine 60 mg/m2 is feasible if no significant toxicities after the first cycle. Clinical efficacy was demonstrated with long-term responders observed.

KW - Administration, Oral

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Breast Neoplasms/drug therapy

KW - Demography

KW - Disease-Free Survival

KW - Dose-Response Relationship, Drug

KW - Female

KW - Humans

KW - Lapatinib

KW - Middle Aged

KW - Neoplasm Metastasis

KW - Quinazolines/adverse effects

KW - Receptor, ErbB-2/metabolism

KW - Treatment Outcome

KW - Vinblastine/administration & dosage

KW - Vinorelbine

U2 - 10.1093/jjco/hyx188

DO - 10.1093/jjco/hyx188

M3 - Article

C2 - 29315394

VL - 48

SP - 242

EP - 247

JO - Japanese Journal of Clinical Oncology

JF - Japanese Journal of Clinical Oncology

SN - 0368-2811

IS - 3

ER -