A phase II study of trastuzumab-DM1 (T-DM1), a HER2 antibody-drug conjugate (ADC), in patients (pts) with HER2+ metastatic breast cancer (MBC): Final results.
C. L. Vogel, H. A. Burris, S. Limentani, R. Borson, J. O’Shaughnessy, S. Vukelja, S. Agresta, B. Klencke, M. Birkner, H. Rugo
Background: T-DM1 is an ADC that combines the biological activity of trastuzumab (T) with targeted delivery of a potent antimicrotubule agent, DM1, to HER2-expressing cancer cells. In a phase I study, T-DM1 was administered IV q3w to pts with HER2+ MBC who had progressed on T + chemotherapy. T-DM1 was well-tolerated at the maximum tolerated dose (MTD) of 3.6 mg/kg, with no reports of cardiac toxicity. The confirmed objective response rate (ORR) for the 9 pts with measurable disease treated at the MTD was 44%. The phase II study described here further assesses tolerability and activity of T-DM1.
Methods: This was a multi-institutional, open-label, single-arm phase II study, to enroll 100 pts. All eligible pts had progressed on HER2-directed therapy and had received chemotherapy in the metastatic setting. T-DM1 was administered at 3.6 mg/kg IV q3w. Primary objectives were assessment of ORR and of safety and tolerability.
Results: As of the August 29, 2008, data-cut, 112 patients had enrolled, with baseline median age 54.5 (range 33–82); ECOG PS 2 or 3, 80%; 68.7% with > 3 sites of metastatic disease; median 3 (range 1–14) prior chemotherapy agents for metastatic disease, median 76.3 weeks prior T, and 55.4% with previous lapatinib. Due to limited F/U, the median number of T-DM1 cycles received was 5 (range 1–16), and 19 of the 107 efficacy evaluable patients had only one post-baseline tumor assessment. Fifty-six pts had discontinued study treatment. With a median follow-up of 4.4 mos, there were 42 (39.3%) ORs (CR or PR), 29 (27.1%) of which have been confirmed by follow-up (F/U) imaging. Among the subgroup of pts who had either >6 months F/U or had discontinued from the study at any time (n = 76) there were 33 ORs (43.4%), 29 (38.2%) of which were confirmed by F/U imaging. The most common grade 3–4 AE was thrombocytopenia (7.1%). Updated data will be presented at the meeting, including updated ORR, 6-month clinical benefit rate, ORR by independent review, progression free survival, and duration of response.
Conclusions: T-DM1 has single agent activity in pts with previously treated, HER2+ MBC, and is well tolerated at the recommended phase II dose.
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