AVOREN: effect of Avastin plus IFN(A type of immunotherapy. A natural substance produced in the body in tiny amounts as part of the immune response. It is given in much larger quantities as treatment to boost the immune system and help fight cancer) on tolerability
Avastin plus IFN is a well tolerated first-line treatment option in mRCC
The majority of the most common AEs(Symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study) in the Avastin plus IFN arm appear to be IFN-related: pyrexia(Fever), anorexia(An emotional disorder characterised by an obsessive desire to lose weight by refusing to eat), fatigue(A state of awareness describing a range of afflictions, usually associated with mental and/or physical and/or weakness (tiredness)) and asthenia
- Low incidence of grade 3/4 AEs.1
- No cumulative toxicity for IFN-associated AEs in patients receiving long-term Avastin (>12 months).2
Avastin-related side effects are most commonly related to the inhibition of VEGF(A protein that promotes angiogenesis and is known to be a prognostic factor in several types of tumour)
- Hypertension(High blood pressure) and proteinuria(The presence of an excess of serum proteins in the urine) are the two most common grade 3/4 events associated with Avastin therapy; however, these events can be effectively managed by standard medical interventions.3
- The majority of bleeding events were low-grade epistaxis(Nosebleed), also effectively managed by standard techniques.3
Avastin plus IFN is a well tolerated regimen with no new toxicities emerging outside of those known for Avastin and IFN.
Characteristic safety profile of Avastin plus IFN
| Avastin + IFN (n=337‡) |
Placebo + IFN (n=304‡) |
|||
|---|---|---|---|---|
| Selected AEs (%)* |
All grades | Grade ≥3 | All grades | Grade ≥3 |
| Pyrexia | 45 |
2 |
43 |
<1 |
| Anorexia | 36 |
3 |
31 |
3 |
| Bleeding | 34 |
3 |
9 |
<1 |
| Fatigue | 33 |
13 |
27 |
8 |
| Asthenia | 33 | 11 | 28 | 7 |
| Hypertension | 29 | 5 | 9 | <1 |
| Flu-like symptoms | 25 | 3 | 26 | 2 |
| Headache | 24 | 2 | 16 | 1 |
| Diarrhoea | 21 | 2 | 16 | <1 |
| Proteinuria | 20 | 8 | 3 | 0 |
| Dyspnoea | 14 | 1 | 13 | 2 |
| Depression | 12 | 3 | 11 | 2 |
| Anaemia | 10 | 3 | 13 | 6 |
| *AEs occurring at a frequency of ≥10% in the Avastin + IFN arm ‡Based on safety population Reprinted from The Lancet, 370, Escudier, et al., 2103–11, 2007 with permission from Elsevier. http://www.thelancet.com/. |
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AVOREN: effect of Avastin plus reduced-dose IFN on tolerability
Avastin plus reduced-dose IFN appears to improve tolerability
Dose reduction of IFN monotherapy(Treatment of a condition by means of a single drug) is routinely used in clinical practice to effectively manage tolerability.
The AVOREN protocol allowed for the dose reduction of IFN from an initial dose of 9MIU to 6 or 3MIU to manage grade ≥3 AEs attributable to IFN1
- 40% of patients randomised(How subjects are assigned to a treatment arm in a study. The treatment a subject receives is determined by chance alone) to Avastin plus IFN received reduced doses of IFN.
Retrospective analysis of AVOREN suggests that Avastin plus reduced-dose IFN improves tolerability
- A lower incidence of IFN-related events was observed during the 6 weeks after IFN dose reduction compared with 6 weeks prior to dose reduction in patients treated with Avastin plus reduced doses of IFN.4
AVOREN: tolerability following IFN dose reduction4,5
Summary
Avastin plus IFN is a well tolerated first-line treatment option in mRCC.
References
- Escudier B, Pluzanska A, Koralewski P, et al. Lancet 2007;370:2103–11.
- Ravaud A, Bajetta E, Bracarda S, et al. Ann Oncol 2008;19(Suppl. 8):viii187 (Abstract 579O).
- Porta C, Szczylik C. Cancer Treat Rev 2009;35:297–307.
- Melichar B, Koralewski P, Ravaud A, et al. Ann Oncol 2008;19:1470–6.
- Escudier B, Cosaert J, Jethwa S. Biologics: Targets and Therapy 2008;2:517–30.