In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 8531-8531
Abstract:
8531 Background: MET and VEGF signaling are implicated in angiogenesis, invasion, and metastasis. Cabozantinib (cabo) is an oral, potent inhibitor of MET and VEGFR2. A RDT evaluated activity and safety in 9 tumor types. Here we report on the metastatic melanoma cohort, including the ocular subtype. 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 phase was progression free survival (PFS). Results: Enrollment to this cohort is complete (n = 77); all pts are unblinded. Baseline characteristics: median age 66 years; melanoma subtype: cutaneous/mucosal 70% and ocular 30%; known BRAF mutation 32%; LDH ≥ 1.1 x upper limit normal 35%; bone metastases 19%; median prior lines of therapy 1 (range 0-5). Median follow-up was 2.8 months (range 0.3 - 25). 35 pts (45%) completed the open-label Lead-in stage with 25 pts randomized to continue cabo (n=12) or to placebo (n=13). Median PFS from randomization was 5.7 months for cabo vs. 3 months for placebo (HR=0.3, p =0.055). Median PFS from Study Day 1 was 4.4 months. The estimate of PFS at month 6 (PFS6) is 44%. Evidence of objective tumor regression was observed in 39/65 pts (60%) with ≥ 1 post-baseline tumor assessment including 11/23 pts (48%) with ocular melanoma. Two bone scan evaluable pts demonstrated partial resolution of bone lesions at wk 6 accompanied by pain relief. Most common Grade 3/4 AEs were fatigue (14%), HTN (9%), constipation (4%), and diarrhea (3%); one related Grade 5 AE of diverticular perforation and peritonitis reported during Lead-in stage. Conclusions: Cabo demonstrates activity in metastatic melanoma pts, regardless of subtypes or BRAF mutation status, with improvement in PFS relative to placebo, and high rates of PFS6 and objective tumor regression. The safety profile of cabo was comparable to that of other VEGFR TKIs.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.8531
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
