Dataset Information

Phase 1 Study of Erlotinib and Metformin in Metastatic Triple-Negative Breast Cancer.

ABSTRACT:

Background

Epidermal growth factor receptor (EGFR) is frequently overexpressed in metastatic triple-negative breast cancer (mTNBC). One strategy for overcoming resistance to EGFR inhibition is concomitant inhibition of downstream signaling. The antidiabetic drug metformin inhibits both MAPK and PI3K/mTOR pathway signaling. We evaluated the combination of erlotinib and metformin in a phase 1 study of patients with mTNBC.

Patients and methods

Patients with mTNBC who had received at least one prior line of therapy for metastatic disease were eligible. Erlotinib dose was fixed at 150 mg daily. Metformin dose escalation was planned according to a 3 + 3 design. Dose-limiting toxicities (DLT) were assessed during the first 5 weeks of therapy. The primary objective was to determine the maximum tolerated dose of metformin with fixed-dose erlotinib. Secondary endpoints were response rate, stable disease rate, and progression-free survival.

Results

Eight patients were enrolled. The median number of prior therapies for metastatic disease was 2.5 (range, 1-6). No DLT events were reported during the DLT assessment period. Most adverse events were grade 1/2. Grade 3 diarrhea despite maximum supportive care required dose reduction of metformin in one patient. Grade 3 rash led to study withdrawal in one patient. No grade 4 adverse events were reported. The best observed response was stable disease in 2 patients (25%). Median progression-free survival was 60 days (range, 36-61 days).

Conclusion

Erlotinib and metformin were well tolerated in a population of pretreated mTNBC patients but did not demonstrate efficacy in this population.

SUBMITTER: Fenn K

PROVIDER: S-EPMC7304226 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Phase 1 Study of Erlotinib and Metformin in Metastatic Triple-Negative Breast Cancer.

Fenn Kathleen K Maurer Matthew M Lee Shing M SM Crew Katherine D KD Trivedi Meghna S MS Accordino Melissa K MK Hershman Dawn L DL Kalinsky Kevin K

Clinical breast cancer 20190829 1

<h4>Background</h4>Epidermal growth factor receptor (EGFR) is frequently overexpressed in metastatic triple-negative breast cancer (mTNBC). One strategy for overcoming resistance to EGFR inhibition is concomitant inhibition of downstream signaling. The antidiabetic drug metformin inhibits both MAPK and PI3K/mTOR pathway signaling. We evaluated the combination of erlotinib and metformin in a phase 1 study of patients with mTNBC.<h4>Patients and methods</h4>Patients with mTNBC who had received at ...[more]

PMID: 31570268

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Dataset Information

Phase 1 Study of Erlotinib and Metformin in Metastatic Triple-Negative Breast Cancer.

Background

Patients and methods

Results

Conclusion

Publications

Phase 1 Study of Erlotinib and Metformin in Metastatic Triple-Negative Breast Cancer.

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