A phase II trial of bevacizumab plus everolimus for patients with refractory metastatic colorectal cancer.

Published

Journal Article

For patients with metastatic colorectal cancer (mCRC), no standard therapy exists after progression on 5-fluorouracil, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab. Preclinical data demonstrated that combined vascular endothelial growth factor and mammalian target of rapamycin inhibition has greater antiangiogenic and antitumor activity than either monotherapy. A phase I study of bevacizumab plus everolimus demonstrated that the combination is safe; activity was seen in several patients with refractory mCRC.Fifty patients with refractory mCRC were enrolled and received bevacizumab at 10 mg/kg every 2 weeks and everolimus at 10 mg orally daily.Of the 50 patients enrolled, the median age was 56 years and the median number of prior regimens was four. Forty-seven patients (96%) had prior bevacizumab exposure and 42 patients (84%) had documented progression on prior bevacizumab-based therapy. Forty-nine patients were evaluable for response; eight patients had minor responses (16%) and an additional 15 patients (30%) had stable disease (SD). No complete or partial responses were seen. The median progression-free survival interval was 2.3 months; however, 26% of patients achieved prolonged SD for ≥6 months, and three patients (6%) were on study for >1 year. The median overall survival duration was 8.1 months. The most common grade 1-2 toxicities were mucositis (68%) and hyperlipidemia (64%). Clinically significant grade ≥3 toxicities included hypertension (14%), fistula/abscess/perforation (8%), mucositis (6%), and hemorrhage (2%).Bevacizumab plus everolimus is generally tolerable but may have risks related to mucosal damage and/or wound healing. Bevacizumab plus everolimus appears to have modest activity in refractory mCRC in patients.

Full Text

Duke Authors

Cited Authors

  • Altomare, I; Bendell, JC; Bullock, KE; Uronis, HE; Morse, MA; Hsu, SD; Zafar, SY; Blobe, GC; Pang, H; Honeycutt, W; Sutton, L; Hurwitz, HI

Published Date

  • January 2011

Published In

Volume / Issue

  • 16 / 8

Start / End Page

  • 1131 - 1137

PubMed ID

  • 21795432

Pubmed Central ID

  • 21795432

Electronic International Standard Serial Number (EISSN)

  • 1549-490X

International Standard Serial Number (ISSN)

  • 1083-7159

Digital Object Identifier (DOI)

  • 10.1634/theoncologist.2011-0078

Language

  • eng