BRiTE: a community-based trial of first-line Avastin in combination with chemotherapy in mCRC*

BRiTE was a US-based, non-randomised(How subjects are assigned to a treatment arm in a study. The treatment a subject receives is determined by chance alone), prospective, observational, multicentre trial of 1,953 community-based patients with mCRC.^1,2

Eligibility criteria were: metastatic(Pertaining to the spread of a disease, usually cancer, from one organ or part to another non-adjacent organ or part) or locally advanced and unresectable CRC, and treatment with Avastin in combination with any first-line chemotherapy.

The chemotherapy regimen and Avastin dose/schedule were selected at the investigator’s discretion.

Patients were followed for at least 3 years and clinical data were updated every 3 months.

• 1,953 patients were enrolled. At final data base lock on 15 October 2008.¹
• Median patient follow-up was 20.1 months.
• 1,537 patients (79%) had documented PD.
• 425 (22%) patients had completed the trial, were alive and progression(A carcinogenic process whereby genetically altered cells undergo a second (non-genetic) cell expansion resulting in uncontrollable growth) free.
• 1,286 (66%) patients had died.
• 150 (8%) patients were lost to follow-up.
• 88 (4%) patients were withdrawn from the trial.

*Data from this study has not been submitted for regulatory review and is not included in the Avastin SmPC

Primary endpoint

• Safety.

Secondary endpoints

• PFS(The time from trial entry to disease progression or death from any cause).
• OS(The time from trial entry to death from any cause).
• 1-year survival(Number of patients who are surviving 1 year after starting treatment) rate.

BRiTE: effect of Avastin on PFS and OS

Estimated median PFS was 9.9 months (95% CI(A range of values used to indicate the reliability of an estimate (or a set of values within which there is a specified probability)): 9.5–10.3).¹

Median OS was 22.9 months (95% CI: 21.9–24.4) and 1-year survival was 74.4% (95% CI: 72.4–76.4).¹

Median PFS with Avastin-containing first-line therapy was generally similar across all patient age subgroups.¹

First-BEAT (MO18024): a large, non-randomised trial of first-line Avastin in combination with chemotherapy in mCRC*

A non-randomised large phase IIIb trial, undertaken in 41 countries, to evaluate the safety and efficacy(The capacity for beneficial change (or therapeutic effect) of a given intervention) of Avastin in a population of patients with mCRC in routine clinical practice.³

Patients were treated with first-line fluoropyrimidine-based chemotherapy (at the physician’s discretion) in combination with Avastin until progression

• Avastin dose was equivalent to 2.5mg/kg/week
  • 5mg/kg every 2 weeks with 5-FU-containing regimens
  • 7.5mg/kg every 3 weeks with Xeloda-containing regimens.

Of the 1,965 patients enrolled, data were available for 1,914 patients.

*Data from this study has not been submitted for regulatory review and is not included in the Avastin SmPC

Primary endpoint

• Safety.

Secondary endpoints

• OS.
• PFS.

First-BEAT: effect of Avastin on OS

As of 1 February 2008, data were available for 1,914 patients (ITT(Usually pertaining to an analysis that is based on the initial treatment intent, not on the treatment eventually administered) population): eligible patients had been followed for a median of 21.2 months (range: 0–43.2 months).

The most common doublet regimens were FOLFOX (29%), FOLFIRI (26%) and XELOX (18%), 16% of patients received monotherapy(Treatment of a condition by means of a single drug) plus Avastin.

The estimated median OS was 22.7 months (95% CI: 21.7–23.8 months).³

Subgroup analysis showed that OS was comparable in patients receiving the different chemotherapy regimens.³

OS was slightly lower in the 5-FU/Xeloda subgroup. However, based on certain baseline characteristics, these patients appeared to have a poorer prognosis than those receiving doublet chemotherapy regimens.³

This analysis of OS is comparable with that observed in the large phase III trials (AVF2107g⁴ and NO16966⁵).

First-BEAT: effect of Avastin on PFS

Median PFS was 10.8 months (95% CI: 10.4–11.3, based on 1,646 events).³

Subgroup analysis showed that PFS was comparable in patients receiving the different chemotherapy regimens, and in general was >10 months, confirming data seen in previous clinical trials.³

PFS was lower in the 5-FU/LV or Xeloda subgroup. However, these patients appeared to have a poorer prognosis compared with those receiving doublet chemotherapy regimens.³

This analysis of PFS is comparable with that observed in the large phase III trials (AVF2107g⁴ and NO16966⁵).

 First-BEAT: efficacy of Avastin in elderly patients

The efficacy of Avastin plus chemotherapy was evaluated by age group (<65, 65–74, and ≥75 years) in patients from First-BEAT.⁶

A total of 1,286 (67%) patients were <65 years, 499 (26%) were 65–74 years and 129 (7%) were ≥75 years.⁶

Median PFS was similar for the <65 and 65–74 years age categories (10.8 and 11.2 months, respectively) and consistent with previous reports.⁶ Median PFS was 10.0 months in patients aged ≥75 years.

Median OS was similar for the <65 and 65–74 years age categories (23.5 and 22.8 months, respectively), but numerically lower in the ≥75 year group (16.6 months), probably due to the small number of patients included in this category.⁶