1199P - A randomised phase II study of cetuximab (C) in combination with two cisplatin-based concurrent chemoradiotherapy regimens in patients (pts) with st...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Cytotoxic agents
Surgical oncology
Non-small-cell lung cancer
Therapy
Biological therapy
Radiation oncology
Presenter Laurent Greillier
Authors L. Greillier1, I. Martel-Lafay2, D. Arpin3, N. Pourel4, S. Chabaud5, R. Lamy6, A. Madroszyk7, P. Fournel8
  • 1Multidisciplinary Oncology & Therapeutic Innovations, Aix-Marseille Univ, Assistance Publique-Hôpitaux de Marseille, Marseille/FR
  • 2Radiotherapy, Centre Leon Berard, Lyon/FR
  • 3Pulmonology, Centre Hospitalier de Macon, Macon/FR
  • 4Radiotherapy, Institut Sainte Catherine, Avignon/FR
  • 5Ubet, Centre Leon Berard, Lyon/FR
  • 6Pulmonology, Centre Hospitalier de Bretagne Sud, Lorient/FR
  • 7Medical Oncology, Institut Paoli Calmettes, Marseille/FR
  • 8Département D'oncologie Médicale, Institut de Cancérologie Lucien Neuwirth, 42271 - Saint-Priest en Jarez/FR

Abstract

Background

This non-comparative randomised trial (EUDRACT 2008-005013-21) aimed to assess the feasibility of combining cetuximab (C) with cisplatin (P) + vinorelbine (V) + radiotherapy (R) or with P + etoposide (E) + R in selected stage IIIA/B NSCLC PTS.

ARM A N (%) ARM B N (%)
PTS with at least one ≥ grade 3 NHTNV 12 (36) 15 (48)
More frequent events
- Esophagitis 2 (6) 8 (26)
- Fatigue 2 (6) 2 (7)
- Thrombosis/embolism 2 (6) 2 (7)
- Acneiform rash 3 (9) -
- Febrile neutropenia - 2 (7)
- Hemoptysis - 1 (3)*

Methods

Eligibility criteria included age <70 years, PS ≤1, weight loss ≤10%, FEV1 ≥40% th, and adequate hematologic, renal and hepatic functions. After inclusion, PTS received on day 1 (D1) 1 cycle of P (75mg/m2) + docetaxel (75mg/m2). On D21, PTS with suitable dosimetric parameters (V20 ≤ 35% and Mean Lung Dose ≤20 Gy) were randomised and received an initial dose of C (400 mg/m2). Between D28 and D71, PTS received a concurrent combination of weekly C (250mg/m2, 7 doses), R (66 Gy/6.5 weeks) and 2 cycles of P (80 mg/m2 D1) + V (15mg/m2 D1, 8) in arm A, or 2 cycles of P (50 mg/m2 D1, 8) + E (50 mg/m2 D1-5) in arm B. The primary endpoint was feasibility, evaluated by the % of PTS developing ≥ grade 3 (NCI-CTCAE v3.0) non-hematologic toxicities, with the exception of nausea and vomiting (NHTNV), during treatment. The planned sample size was 31 randomised PTS per arm. Secondary endpoints were PFS, compliance, safety and response evaluated at D113. Toxicities and responses were centrally reviewed.

Results

Ninety PTS were enrolled and 64 PTS were randomised: 33 in arm A, 31 in arm B. The major reason for non-randomisation was dosimetric failure at D21. 27 PTS experienced ≥ grade 3 NHTNV (Table). The rate of serious adverse events was 30% in arm A and 55% in arm B. Objective response rate and PFS rate at 1 year were 79% and 57% (95%CI: 36-73), respectively, in arm A and 69% and 43% (95%CI: 20-64), respectively, in arm B.

Conclusion

The concurrent association of C with P-based chemoradiotherapy seems to be safe and active in both arms, with a slight advantage for arm A, and deserves further evaluation in a phase III study.

*, grade 5.

Disclosure

All authors have declared no conflicts of interest.