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Veliparib and Lapatinib in patients with metastatic, triple negative breast cancer


Triple-negative breast cancer ( TNBC ) is an aggressive subtype of breast cancer, often resistant to standard of care therapies.
An induced synthetic lethal interaction with combined EGFR ( epidermal growth factor receptor ) and PARP ( Poly ( ADP-ribose )-polymerase ) inhibition in TNBC cells, was previously shown.

A pilot clinical trial using Lapatinib ( Tyverb ) and Veliparib in patients with locally advanced unresectable or metastatic TNBC, was performed.

Researchers have reported safety results and clinical activity of the combination of Veliparib and Lapatinib.

Key eligibility criteria include histologically confirmed TNBC ( ER negative, PR negative, HER-2-Neu negative ), measurable disease, failed anthracyclines and taxanes in the neoadjuvant, adjuvant, or metastatic setting, left ventricular ejection fracture greater than or equal to 50, and ECOG PS of 0-2.

Patients with known germline BRCA 1 or 2 mutations were excluded.

Eligible patients received continuous doses of Lapatinib 1250 mg PO ( per os ) daily and Veliparib 200 mg PO twice daily.
Dose limiting toxicity ( DLT ) evaluation period was 28 days ( cycle 1 ).
Adverse events were assessed by CTCAE v4.03 and best objective response per RECIST v1.1.

Twenty patients were enrolled and 17 were evaluable for response. The median number of prior therapies for advanced breast cancer was 1 ( range 0-2 ).
Fifty percent of the patients enrolled were Caucasian, 45% African-American, and 5% Hispanic.

Of the evaluable patients, 4 had a partial response and 2 had stable disease.

There were no dose-limiting toxicities. The majority of toxicities occurred during cycles 2 and 3. Toxicities were manageable.
Most adverse events were limited to grade 1 or 2 ( no grade 5 ).
Common treatment-related adverse effects were fatigue ( 6.4% ), diarrhea ( 5.1% ), constipation ( 5.5% ), insomnia ( 4.5% ), vomiting ( 2.9% ), anemia ( 2.6% ), headache ( 2.6% ), dizziness ( 2.3% ), dyspnea ( 2.3% ), and rash ( 2.3% ).

In conclusion, Lapatinib plus Veliparib in the treatment of advanced triple-negative breast cancer resistant to standard of care has a manageable safety profile and promising antitumor activity. Further investigation of EGFR inhibition in combination with a PARP inhibitor is needed. ( Xagena )

Source: American Society of Clinical Oncology - ASCO Meeting, 2018

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