Efficacy in CRC

Avastin plus IV 5-FU–containing chemotherapy: expanding the survival standard in MCRC

Significant survival benefit in both first- and second-line treatment

Efficacy overview

In both first- and second-line MCRC, Avastin-based therapy has demonstrated superior survival results over chemotherapy alone. Avastin, in combination with IV 5-FU–containing chemotherapy, is the only biologic agent proven to extend survival in first- or second-line MCRC.

Results from randomized clinical trials1-4

Avastin Efficacy - Results from randomized clinical trials

  • *Difference statistically significant.
  • †Phase III trial evaluating placebo plus IFL (Arm 1) and Avastin 5 mg/kg q2w plus IFL (Arm 2).
  • ‡Combined analysis of 3 randomized, controlled trials comparing Avastin 5 mg/kg q2w plus IV 5-FU/LV vs a “combined control” of IV 5-FU/LV or IFL alone.
  • §Phase III trial of patients previously treated with irinotecan and 5-FU evaluating FOLFOX4 (Arm 1) and Avastin 10 mg/kg q2w plus FOLFOX4 (Arm 2).
Survival benefits observed with Avastin continued until disease progression per study protocol

Per MCRC study protocols, Avastin administration was continued until disease progression and was not modified due to chemotherapy-related toxicity or stopped when tumor response or disease stabilization was achieved. As demonstrated in Study 2107 and Study E3200, Avastin plus IV 5-FU/LV could be maintained following titration or discontinuation of combination chemotherapy due to increased toxicity. 2,4,5

MCRC trial protocols2,5

Avastin Efficacy - MCRC trial protocols

Safety overview

The most serious adverse events associated with Avastin across all trials were GI perforation, wound healing complication, hemorrhage, non-GI fistula formation, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome, neutropenia and infection, nephrotic syndrome, and congestive heart failure.1

Avastin has demonstrated a positive benefit-risk ratio across MCRC regimens, including FOLFOX4, IFL, and IV 5-FU/LV. In second-line MCRC, Avastin 10 mg/kg q2w plus FOLFOX4 maintained a safety profile consistent with Avastin 5 mg/kg q2w plus IFL in first-line treatment, while significantly extending overall survival.1,2,4

Efficacy across patient types and regimens

In clinical trials, Avastin has demonstrated efficacy across a range of patient types and chemotherapy regimens. In particular, Avastin has demonstrated significant clinical benefits with combination chemotherapy regimens—including IFL (Study 2107) and FOLFOX4 (Study E3200)—as well as with IV 5-FU/LV alone (studies 2107, 2192, and 0780).1-4,6,7 Therefore, Avastin-based therapy may be an appropriate choice for a range of patients, including those who are not considered candidates for more intensive chemotherapy.

Next: In Combination with IFL

Boxed WARNINGS and Additional Important Safety Information

Gastrointestinal (GI) perforation: Avastin administration can result in the development of GI perforation, in some cases resulting in fatality. GI perforation, sometimes associated with intra-abdominal abscess, occurred throughout treatment with Avastin. Permanently discontinue Avastin therapy in patients with GI perforation.

Wound healing complication: Avastin administration can result in the development of wound dehiscence, in some instances resulting in fatality. Permanently discontinue Avastin therapy in patients with wound dehiscence requiring medical intervention. The appropriate interval between termination of Avastin and subsequent elective surgery has not been determined.

Hemorrhage: Severe, and in some cases fatal, pulmonary hemorrhage can occur in patients with NSCLC treated with chemotherapy and Avastin. Do not administer Avastin to patients with recent hemoptysis (≥1/2 tsp of red blood). Permanently discontinue Avastin in patients with serious hemorrhage and initiate aggressive medical management.

Additional serious adverse events included non-GI fistula formation, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome, neutropenia and infection, nephrotic syndrome, and congestive heart failure.

The most common grade 3–5 (nonhematologic) and 4–5 (hematologic) events that may have occurred in Avastin indications (first-line NSCLC, first- and second-line MCRC) included neutropenia, fatigue, hypertension, infection, hemorrhage, asthenia, abdominal pain, pain, deep vein thrombosis, intra-abdominal thrombosis, syncope, diarrhea, constipation, leukopenia, nausea, vomiting, dehydration, ileus, neuropathy–sensory, neurologic–other, and headache.

Please see full Prescribing Information, including Boxed WARNINGS, for additional safety information.

References
  1. Avastin Prescribing Information. Genentech, Inc. March 2008.
  1. Hurwitz H, Fehrenbacher L, Novotny W, et al. N Engl J Med. 2004;350:2335-2342.
  1. Kabbinavar FF, Hambleton J, Mass RD, et al. J Clin Oncol. 2005;23:3706-3712.
  1. Giantonio BJ, Catalano PJ, Meropol NJ, et al. J Clin Oncol. 2007;25:1539-1544.
  1. Data on file. Genentech, Inc.
  1. Kabbinavar F, Hurwitz HI, Fehrenbacher L, et al. J Clin Oncol. 2003;21:60-65.
  1. Kabbinavar FF, Schulz J, McCleod M, et al. J Clin Oncol. 2005;23:3697-3705.