Phase II pilot results of imatinib mesylate with weekly docetaxel in metastatic breast cancer

Abstract

1090 Background: Imatinib mesylate (G) is a potent tyrosine kinase inhibitor of platelet derived growth factor receptor (PDGFR), c-KIT, and bcr/abl. PDGFR signaling regulates interstitial tumor pressure enhancing tumor drug delivery and effects. This phase II pilot evaluates the feasibility, toxicity, and efficacy of imatinib with weekly docetaxel as a strategy to potentiate docetaxel in metastatic breast cancer (MBC). Methods: Eligibility: 0–1 regimens for MBC, > 6 months from prior adjuvant taxanes, measurable disease, ECOG PS 0–2, adequate organ function, < G2 neuropathy. Treatment: Docetaxel 30 mg/m2 IV days 1, 8 and 15 q28 with G 600 mg QD. After the first 14 pts, G was decreased to 400 mg in the remaining 19 pts. Response evaluations were every q 8 wks. Following 6 cycles of therapy, pts with SD or better continued maintenance G until PD. Results: 33 pts are evaluable for toxicity. Median age 58 (38–82), ECOG PS 0–18, PS 1–14 pts. 49% ER-/PR- and 79% HER2 neg. 61% had metastases in > 2 visceral sites with lung predominating 42%. 55% received therapy 1st line and 42% as 2nd-line. 13 pts had prior taxanes of which 70% were treated 2nd-line. Hematologic toxicity was mild with G3/4 neutropenia 12%, anemia 9%; 1 pt with febrile neutropenia. G3/4 nonhematologic toxicity consisted of fatigue 27% and GI toxicity prompting G dose modification to 400 mg after the first 14 pts. Despite the lower G dose, the GI events remained distributed equally between the 600/400 mg G doses: G3/4 diarrhea 21% (4/3), nausea 18% (4/2), vomiting 12% (2/3), anorexia 6% (1/1) 22 pts required hospitalizations, 9 treatment related (GI toxicity 4, febrile neutropenia 1, pleural effusion 2, pneumonia 2), 2 other, and 11 due to progression. Median # of cycles was 3 (1.5 - 12.5). 5 pts went on to maintenance G with a median of 6 cycles and 2 remain on maintenance G. 4 of 18 evaluable pts (12%) had PRs, 8 pts had SD, and 6 pts progressed. 11 pts were not evaluable and responses unknown in 4 pts. Median time to progression and overall survival were 3 and 10 months respectively. Conclusions: Imatinib with docetaxel is associated with significant GI toxicity, despite G dose modification to 400 mg daily. No therapeutic advantage for the addition of imatinib to weekly docetaxel in MBC was evident. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Genentech Bristol-Myers Squibb, Eli Lilly and Company, Genentech, GlaxoSmithKline, GPC Biotech, Novartis, sanofi-aventis