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AVAiL (BO17704): phase III trial – efficacy(The capacity for beneficial change (or therapeutic effect) of a given intervention) of Avastin maintained

AVAiL: phase III, randomised(How subjects are assigned to a treatment arm in a study. The treatment a subject receives is determined by chance alone), placebo-controlled(A way of testing a medical therapy in which, in addition to a group of subjects that receives the treatment to be evaluated, a separate control group receives a sham "placebo" treatment which is specifically designed to have no real effect) trial of first-line Avastin plus cisplatin/gemcitabine in patients with previously untreated, non-squamous(Pertaining to cells not from squamous epithelium; relatively common, locally invasive and occasionally metastatic) NSCLC

Phase III, multicentre, randomised placebo-controlled trial of first-line Avastin in patients with previously untreated, advanced or recurrent non-squamous NSCLC.1

All patients received six cycles of chemotherapy: cisplatin (80mg/m2) on day 1 and gemcitabine (1,250mg/m2) on days 1 and 8.

Patients were randomised to receive one of the following (from day 1)

  • Avastin 7.5mg/kg every 3 weeks plus chemotherapy until PD (n=345).
  • Avastin 15mg/kg every 3 weeks plus chemotherapy until PD (n=351).
  • Placebo plus chemotherapy every 3 weeks until PD (n=347).

The trial was not designed to compare the two Avastin doses directly, but to compare each of the Avastin doses with placebo.


Primary endpoint

  • PFS(The time from trial entry to disease progression or death from any cause) (Note: the two Avastin-containing arms were compared with the chemotherapy only arm and not with each other).

Secondary endpoints

  • ORR(The proportion of patients with defined tumour shrinkage; generally the sum of partial responses plus complete responses).
  • Duration of response(The length of time after treatment that a patient remains in complete or partial remission).
  • OS(The time from trial entry to death from any cause).
  • Safety.

AVAiL: Avastin-based therapy significantly increases PFS

AVAiL: both doses of Avastin significantly increased PFS compared with placebo

The addition of cisplatin/gemcitabine to Avastin significantly increased PFS versus placebo plus cisplatin/gemcitabine1

  • Avastin 7.5mg/kg: HR(An estimate of relative risk of an event occurring)=0.75; p=0.0026.
  • Avastin 15mg/kg: HR=0.82; p=0.0301.

AVAiL: continued PFS benefit in the maintenance phase (an exploratory retrospective analysis)2

In AVAiL, Avastin was given with cisplatin/gemcitabine for six cycles and then as a single agent until PD (maintenance).

A retrospective analysis of AVAiL investigated PFS following Avastin or placebo in the maintenance phase of this trial (i.e. PFS was measured from the end of the Avastin/placebo plus cisplatin/gemcitabine phase to PD or death).

Avastin used as single-agent maintenance therapy appears to confer clinical benefit beyond the chemotherapy phase.

PFS was measured from last day of last cycle of cisplatin/gemcitabine plus Avastin/placebo to PD or death.

AVAiL: Avastin-based therapy provides consistent efficacy across patient populations

In the ITT(Usually pertaining to an analysis that is based on the initial treatment intent, not on the treatment eventually administered) population, the median OS was the longest ever reported in NSCLC trials

  • 13.6 and 13.4 months in the Avastin 7.5mg/kg and Avastin 15mg/kg group respectively, versus 13.1 months for placebo.3

Majority of patients (approximately 62%) received multiple lines of post-trial treatment; this was considered to be a confounding factor for the OS analysis.


AVAiL: Avastin-based therapy significantly increases ORR

Both doses of Avastin significantly increased response rate compared with placebo

ORR was significantly increased with both Avastin doses versus placebo1,3

  • This finding is consistent with the ECOG 4599 trial.

The duration of response was significantly longer for patients in the Avastin-containing arms.1

References

  1. Reck M, von Pawel J, Zatloukal P, et al. J Clin Oncol 2009;27:1227–34.
  2. Mezger J, von Pawel J, Reck M. J Clin Oncol 2009;27:e19001.
  3. Reck M, von Pawel J, Zatloukal P, et al. Ann Oncol 2010; 21:1804–9.
  4. Sandler A, Gray R, Perry MC, et al. N Engl J Med 2006;355:2542–50.

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