BEVACIZUMAB (BEV) + LOW-DOSE INTERFERON-α2A (IFN) FOR FIRST-LINE TREATMENT OF METASTATIC RENAL CELL CARCINOMA (MRCC): FINAL SAFETY AND EFFICACY DATA FROM THE PROSPECTIVE BEVLIN STUDY

Konference: 2012 37th Congress ESMO – účast ČR

Kategorie: Genitourinární nádory

Téma: Poster, Poster presentation I

Číslo abstraktu: 809P

Autoři: prof. MUDr. Bohuslav Melichar, Ph.D.; Sergio Bracarda; Vsevolod Matveev; Prof.MD Andrey Kaprin; MD Boris Alekseev; Dr. R. Janciauskiene; Beatrix Lutiger; Prof. Martin E. Gore; Prof. Gerald H. Mickisch; MD Joaquim Bellmunt

Background

In the AVOREN trial, first-line BEV + IFN (9 MIU three times in a week [tiw]) was effective in patients (pts) with mRCC. A retrospective analysis found that efficacy was maintained and IFN-related toxicity was improved in pts with IFN dose reduced to 6 or 3 MIU. BEVLiN (MO21609) prospectively assesses the safety and efficacy of BEV with low-dose IFN (3 MIU) in mRCC.

Methods

BEVLiN is an open-label single arm, multinational phase 2 study. Nephrectomized, treatment-naive pts with clear cell mRCC and favourable/intermediate Motzer scores were treated with BEV 10mg/kg q2w + IFN 3 MIU tiw until disease progression. BEVLiN was designed to allow descriptive, cross-trial comparison with the BEV + IFN 9 MIU-treated favourable/intermediate Motzer score AVOREN subgroup. Primary end points are safety (specific grade [Gr] ≥3 IFN-associated adverse events [AEs]) and progression-free survival (PFS). Secondary end points are overall survival (OS); overall response rate (ORR); any Gr ≥3, overall, and serious AEs.

Results

147 pts were enrolled in BEVLiN. Baseline pt characteristics were similar to the comparator AVOREN subgroup. The median follow-up was 29.4 months. Pts received a median of 22.5 cycles of BEV (18.0 in the AVOREN subgroup). Median PFS was 15.3 mos (95% CI: 11.7; 18.0) vs 10.5 mos (95% CI: 10.1; 12.9); median OS was 30.7 mos (95% CI: 25.7; not reached) vs 25.8 mos (95% CI: 22.7; 29.4); and ORR was 29% vs 36% in BEVLiN and the AVOREN subgroup, respectively. The rates of any-Gr and Gr ≥3 IFN-associated AEs were markedly lower in BEVLiN than in the AVOREN subgroup (Table). Overall rates of AEs of special interest were similar between studies, despite longer BEV duration in BEVLiN.

AE, % (95% CI) BEVLiN n = 146a AVOREN subgroup n = 283a
  Any Gr Gr ≥3 Any Gr Gr ≥3
Any IFN-related AE 53 (45–62) 10 (6–16) 89 (85–92) 27 (22–32)
· Asthenia/fatigue 37 (29–45) 10 (5–16) 63 (57–68) 21 (16–26)
· Pyrexia 19 (13–27) 0 (0–2) 45 (39-51) 2 (1–4)
· Nausea 9 (5–15) 1 (0–4) 29 (23–34) 1 (0–3)
· Anorexia 0 (0–2) 0 (0–2) 36 (30–42) 3 (1–5)
Any BEV-related AE of special interestb 59 (50–67) 23 (17–31) 60 (54–66) 23 (18–28)

aTreated pts. bIncludes hypertension, proteinuria, bleeding, and other AEs.

Conclusions

Use of low-dose IFN with BEV in BEVLiN resulted in a reduction in IFN-related AEs without compromising efficacy outcomes compared with a control AVOREN subgroup.


Disclosure

B. Melichar: Dr. Bohuslav Melichar has received honoraria for lectures from Roche and participated in an advisory board meeting.

S. Bracarda: Dr. Sergio Bracarda is an Advisory Board Member for Novartis, Pfizer, GSK, Bayer, Aveo/Astellas, Jannsen &Jannsen and Sanofi-Aventis. He has received honoraria for lectures from Novartis, Sanofi-Aventis and Pfizer.

R. Janciauskiene: Dr. Janciauskiene has been principal investigator in a Hoffmann-La Roche sponsored trial and has been an invited speaker for Hoffmann-La Roche.

B. Lutiger: Beatrix Lutiger is an employee of F. Hoffmann-La Roche AG.

M.E. Gore: Dr. Martin Gore has participated advisory board meetings and is on the speaker's bureau for Roche.

G. Mickisch: Dr. Gerald Mickisch is a member of the BEVLiN Steering Committee.

J. Bellmunt: Dr. Joaquim Bellmunt has participated in an advisory board meeting, and received a lectures fee from Roche.

All other authors have declared no conflicts of interest.

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Datum přednesení příspěvku: 29. 9. 2012