N0234: Phase II study of erlotinib (OSI-774) plus gemcitabine as first-or second-line therapy for metastatic breast cancer (MBC)

Abstract

644 Background: Based on favorable preclinical interaction of the HER1 inhibitor erlotinib with chemotherapy, and previously demonstrated single agent activity of gemcitabine as therapy for metastatic breast cancer (MBC), a phase II study of the combination was conducted by the North Central Cancer Treatment Group. Goals were to evaluate the anti-tumor activity and tolerability of erlotinib 150 mg P.O. daily in combination with gemcitabine at 1000 mg/m2 days 1 and 8 of 21 day cycles. Eligibility: MBC, measurable disease as defined by RECIST. Prior adjuvant chemotherapy and up to 1 prior chemotherapy for MBC allowed (1 of which had to include an anthracycline or taxane). Results: 59 evaluable patients were enrolled. Patient characteristics: median age: 57 (range: 28–82), prior adjuvant chemotherapy (68%), prior anthracycline (81%), prior taxane (78%), prior anthracycline and taxane (61%); 0 prior chemotherapy for MBC (44%), 1 prior chemotherapy for MBC (56%). Median number of cycles treatment administered: 4 (range: 1–17). Severe (CTC grade 3/4) hematologic adverse events: neutropenia (35%), thrombocytopenia (9%), and anemia (7%). Severe (CTC grade 3/4) non-hematologic adverse events: fatigue (14%), dyspnea (12%), diarrhea (9%), rash (7%), and infection (4%). 10 pts are still receiving study treatment (tx). Reasons for discontinuing tx: disease progression (76%), patient refusal (12%), adverse event (4%), new primary (2%), symptomatic deterioration (4%), and patient no return (2%). Response: 8 partial responses for an overall response rate of 14% (95% CI: 6–25%). Median duration of response was 4.6 months. At last contact, 12 pts were alive without progression and 28 alive with progression (median length of follow-up 4.3 months; max follow-up of 12 months), and 19 died. Median PFS was 2.8 months (95%CI: 1.9–4.2 months). The 6-month survival rate was 75% (95%CI: 63–89%). Conclusions: The combination of Erlotinib plus gemcitabine was well tolerated. This combination has lower than expected activity as 1st or 2nd-line therapy for MBC, based on historical controls of gemcitabine based combination treatment. Partial support by Breast Cancer Research Foundation and NIH (CA25224). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, Genentech, Pfizer