In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 535-535
Kurzfassung:
535 Background: Dysregulation of MET and VEGF signaling has been implicated in breast cancer development and progression, including tumor invasion and dissemination. Cabozantinib (cabo) is an oral, potent inhibitor of MET and VEGFR2. A RDT evaluated activity and safety in 9 tumor types, including MBC. Methods: Eligible patients (pts) were required to have progressive measurable disease per RECIST. Pts received cabo at 100 mg qd over a 12 wk Lead-in stage. Tumor response (mRECIST) was assessed q6 wks. Treatment ≥ wk 12 was based on response: pts with PR continued open-label cabo, pts with SD were randomized to cabo vs placebo, and pts with PD discontinued. Primary endpoint in the randomized discontinuation phase was progression-free survival (PFS). Results: Enrollment to this cohort is complete (n = 45); all pts are unblinded. Baseline characteristics: median age 56; invasive ductal 86%, invasive lobular 7%; ER+ 93%, HER2+ 18%, triple- 5%; visceral disease 91%; bone metastases 73%; median prior lines of therapy 3 (range 1-8), including 71% with prior anthracyclines. Median follow-up was 2.9 mos (range 0.1 -16). 21 pts (47%) completed Lead-in stage with only 9 randomized to continue cabo (n = 5) or placebo (n = 4). Median PFS from Study Day 1 was 4.1 mos. At wk 12, objective response rate was 14% and disease control rate 48%. Tumor regression was observed in 25/39 pts (64%) with ≥1 post-baseline tumor assessment. 4/10 pts evaluable by bone scan had partial resolution of bone lesions. Of 12 pts receiving narcotics for bone pain, 5 pts reported improved pain and 2 pts had decreased narcotics use, per investigator. 4/14 evaluable pts (29%) with bone metastases experienced ≥50% decline in serum NTx. Most common Grade 3/4 AEs were palmar-plantar erythrodyesthesia (13%) and fatigue (11%). One related Grade 5 AE of respiratory compromise was reported during the Lead-in stage. Conclusions: Cabo demonstrated a 14% rate of objective tumor regression in heavily pretreated MBC pts. Observed effects on bone scan and pain are consistent with those seen in other malignancies. The safety profile of cabo was comparable to that seen with other VEGFR TKIs.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.535
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2012
ZDB Id:
2005181-5
