1299P - Phase II study of bevacizumab in combination with 1st-line chemotherapy or 2nd-line erlotinib in non-squamous NSCLC (NS-NSCLC) patients with asympto...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anticancer agents
Non-small-cell lung cancer
Therapy
Biological therapy
Presenter Benjamin Besse
Authors B. Besse1, S. Le Moulec2, H. Senellart3, J. Mazières4, F. Barlesi5, E. Dansin6, G. Robinot7, M. Perol8, D. Moro-Sibilot9, J. Soria10
  • 1Dept. Of Medicine, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 2Oncologie Medicale, Hôpital d'Instruction des Armées du Val-de-Grâce, Paris/FR
  • 3Medical Oncology, Institut De Cancérologie De l'Quest, Site René Gauducheau, Nantes/FR
  • 4Department Of Thoracic Oncology, Hôpital De Larrey, Toulouse/FR
  • 5Service D'oncologie Multidisciplinaire Et Innovations Thérapeutique, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille/FR
  • 6Department Of Medical Oncology, CLCC OSCAR Lambret, Lille/FR
  • 7Institut De Cancerologie, Centre Hospitalier Universitaire, Brest/FR
  • 8Medical Oncology, Hôpital de la Croix-Rousse, Lyon/FR
  • 9Thoracic Oncology Unit, Hôpital A. Michalon, Grenoble/FR
  • 10Department Of Cancer Medicine, Institut Gustave Roussy, Villejuif/FR

Abstract

Background

Brain metastases (BM) occur in up to 56% of pts with advanced cancer and are no longer a contraindication to bevacizumab treatment based on safety data. The non-comparative phase II BRAIN trial (NCT00800202) is the first study to assess the efficacy/safety of bevacizumab in combination with systemic treatments in ns-NSCLC pts with untreated BM.

Methods

Eligible pts (stage IV ns-NSCLC; PS 0–1; untreated, asymptomatic BM; ineligible for surgery/radiosurgery) received: arm A (n = 67),1st-line bevacizumab (15mg/kg q3w until progression/unacceptable toxicity) plus carboplatin (AUC 6 q3w, ≤6 cycles) and paclitaxel (200mg/m2 q3w, ≤6 cycles) (B + CP); or arm B (n = 24), bevacizumab (as above) plus erlotinib (150mg/day until progression/unacceptable toxicity) (B + E) in 2nd line. Primary endpoint: 6-month progression-free survival (PFS) by treatment arm. Secondary endpoints: response rate (RR; RECIST v1.1), overall survival (OS) and safety. The trial could be halted if the incidence of brain haemorrhage (ICH) was >3 in B + CP or >2 in B + E. All sites of disease were assessed every 6 weeks including mandatory MRI for BM assessment.

Results

Pt baseline characteristics and outcomes are shown (Table). Efficacy: the observed 6-month PFS was 56.5% (B + CP) and 58.0% (B + E). Safety: ICH frequency comparable to previously published data in a similar pt population (B + CP, n = 1 grade 1; B + E, n = 0). Grade 3–5 adverse events of special interest (AESI) were seen in 19.4% (B + CP) and 20.8% (B + E) of pts. No erlotinib-related grade 3–5 AESIs were seen. There were 3 AEs leading to death (1 epilepsy, B + CP; 1 hypertensive encephalopathy, 1 ischaemic stroke, B + E).

Conclusion

Bevacizumab with 1st-line chemotherapy or 2nd-line erlotinib demonstrated efficacy and acceptable safety in pts with ns-NSCLC with asymptomatic untreated brain metastases when compared to historical controls. Baseline characteristics and clinical outcomes for patients in the BRAIN study.

B + CP B + E
n = 67 n = 24
Baseline characteristics
Gender, n (%) Male 46 (68.7) 11 (45.8)
Female 21 (31.3) 13 (54.2)
Median age, years (range) 61.0 (40–79) 54.0 (34–70)
ECOG performance status, n (%) 0 37 (55.2) 13 (54.2)
1 30 (44.8) 11 (45.8)
WHO histology, n (%) Adenocarcinoma 59 (88.1) 23 (95.8)
Large-cell carcinoma 8 (11.9) 1 (4.2)
Recurrence, n (%) No 61 (91.0) 13 (54.2
Yes 6 (9.0) 11 (45.8)
Clinical outcomes (95% CI)
6-month PFS, % 56.5 (43.8–67.4) 58.0 (36.0–74.8)
Median PFS, months 6.7 (5.7–7.1) 6.3 (2.5–8.4)
Median OS, months 15.1 (11.8–NR) 13.6 (7.5–26.3)
12-month OS, % 62.8 (49.7–73.4) 50.7 (28.7–69.0)
18-month OS % 41.1 (27.4–54.3) 40.5 (20.2–60.0)
Overall RR, % 62.7 (50.0, 74.2) 12.5 (2.7, 32.4)
RR, % Intracranial metastases 61.2 (48.5–72.9) 20.8 (7.1–42.2)
Extracranial metastases 64.2 (51.5–75.5) 12.5 (2.7–32.4)

NR = not reached

Disclosure

B. Besse: Received grants from Roche.

H. Senellart: Attended advisory boards.

F. Barlesi: Attended adivsory boards for Roche. Received research funding from Roche.

E. Dansin: Attended advisory boards for Roche, Lilly and Boehringer-Ingelheim.

M. Perol: Attended advisory boards for Roche, Pfizer, Lilly and Boehringer-Ingelheim.

D. Moro-Sibilot: Attended adivsory boards for Roche, Pfizer and Lilly. Received reserarch funding from Roche, Pfizer, Lilly, Astra Zeneca and BIF. Substantive Relationships with Roche, Pfizer, Lilly, Astra Zeneca and BIF.

J. Soria: Attended Roche Advisory board.

All other authors have declared no conflicts of interest.