Bevacizumab (B) plus everolimus (E) in refractory metastatic colorectal cancer (mCRC).

4080 Background: For patients (pts) with mCRC, no standard therapy exists after progression on 5-FU, oxaliplatin, irinotecan, bevacizumab, and/or cetuximab/panitumumab. Preclinical data demonstrate combined VEGF and mTOR inhibition has greater anti-angiogenic and anti-tumor activity than either monotherapy. B inhibits VEGF; E inhibits mTOR. Phase I data in patients demonstrated B + E was safe and activity was seen in several pts with refractory mCRC. METHODS: 25 pts with refractory mCRC were enrolled in an expanded cohort of B + E. Doses: B 10 mg/kg q2 wks; E 10 mg PO QD. Blood, skin, and tumor biopsies pre- and on-treatment were collected for markers of response and resistance. RESULTS: At this time, 19 pts (10M: 9F) are evaluable for toxicity; 17 for efficacy. Median age 57 years (range 35-78). Median number prior regimens 3. All pts had prior B exposure; 17 pts had progressive disease on prior B-based therapy. There was one Grade (Gr) 4 adverse event (AE) of hypokalemia. Grade 3 AE related to treatment were bowel perforation/fistula, (n=2), hyperglycemia (3), hypokalemia (3), hypertension (2), fatigue (1), alk phos elevation (1; lab only), hypoalbuminemia (1), and volume depletion (1). Other events of interest were: Gr1-2 mucositis (n=10), Gr1 hyperlipidemia (11). Of 17 pts evaluable for response, 4 pts had SD as best response (median 24 wks, range 17-31+ wks); there were 3 minor responses in pts who had progressed on B (median 16 wks, range 16-27 wks). No CR or PR were seen. Biomarker data is pending. CONCLUSIONS: B+E has activity in refractory mCRC in pts who had progressed on a B-based regimen, suggesting B+E may overcome resistance to B. Patient accrual is continuing and updated data will be presented. [Table: see text].

Duke Scholars

Author Hope Elizabeth Uronis Medicine, Medical Oncology

Author Michael Aaron Morse Medicine, Medical Oncology

Author Gerard Conrad Blobe Medicine, Medical Oncology

Author Syed Yousuf Zafar Medicine, Medical Oncology

Author Andrew Benjamin Nixon Medicine, Medical Oncology