LBA29 - A randomized phase II study comparing erlotinib (E) versus E alternating with chemotherapy in relapsed non-small cell lung cancer (NSCLC) patients....

Date 30 September 2012
Event ESMO Congress 2012
Session NSCLC, metastatic I
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Joachim Aerts
Authors J.G. Aerts1, H. Codrington2, S. Burgers3, B. Biesma4, O. Dalesio5, A.C. Dingemans6, A.D. Vincent5, H.J.M. Groen7, E.F. Smit8
  • 1Pulmonary Diseases, Amphia Hospital, 4818CK - Breda/NL
  • 2Pulmonary Diseases, Haga Hospital, s Gravenhage/NL
  • 3Pulmonary Diseases, Antoni van Leeuwenhoek Hospital, amsterdam/NL
  • 4Pulmonary Diseases, Jeroen Bosche ziekenhuis, 's hertoghenbosch/NL
  • 5Biometrics, Antoni van Leeuwenhoek Hospital, Amsterdam/NL
  • 6Pulmonology, Maastricht University Medical Center (MUMC), NL-6202 AZ - Maastricht/NL
  • 7Pulmonary Diseases, University Hospital Groningen (UMCG), NL-9700 RB - Groningen/NL
  • 8Dept. Of Pulmonary Diseases, Vrije University Medical Centre (VUMC), NL-1081 HV - Amsterdam/NL

Abstract

Introduction: Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) administered concurrently with chemotherapy did not improve outcome. However, in preclinical models and early phase non-comparative studies pharmacodynamic separation of chemotherapy and TKIs did show a synergistic effect.

Methods: A randomized open label phase II study was performed in pts with advanced NSCLC who had progressed on or following first-line platinum containing chemotherapy. Pts received E monotherapy 150 mg daily (Arm A) or E 150 mg from day 2 to 16 of the 21 day cycle during 4 cycles of docetaxel for squamous (SQ) or pemetrexed for non-squamous (NSQ) pts (Arm B). After completion of chemotherapy E was continued as a daily regimen until PD. Primary endpoint is progression-free survival (PFS). Secondary endpoints include toxicity and overall survival (OS). Subgroup analysis for the SQ and NSQ was preplanned. The study was designed with 80% power to detect a 33% decrease in the hazard of progression (alpha = 0.05 two sided log rank test).

Results: Between March 2009 and December 2011, 231 patients were randomized, 115 in arm A (42 SQ, 73 NSQ) and 116 in arm B (35 SQ, 81 NSQ). The adjusted HR for PFS for all patients is 0.80 (95% CI 0.60 - 1.06), p=0.12, for OS 0.68 (95% CI 0.50 - 0.94), p=0.02. Toxicity gr 3+ occurred in 19 % (arm A) and 55% (arm B), most frequent rash (7 vs 15%, resp). Febrile neutropenia was 0 vs 6%, resp.

all patients squamous

non

squamous

mono combi mono combi mono combi

male/

female(%)

65/35 63/37 74/26 77/23 60/40 56/44

age (med.

range

64

(38-81)

63

(40-81)

66

(53-81)

64

(51-80)

62

(38-79)

62

(40-82)

ECOG PS 0/1/2/ (%) 34/58/8 43/50/8 31/64/5 37/57/6 36/55/10 45/46/9
PFS months
(median; 95% CI).

4.9

(4.2-6.3)

6.1

(4.8-7.9)

4.9

(3.8-8.0)

4.1

(2.9-8.2)

4.9

(3.9 - 7.6

7.2

(5.3-9.1)

OS months

(median; 95% CI).

5.5

(4.5-8.5)

7.8

(6.5-10.4)

6.2

(4.5-9.8

6.1

(4.1-11.7)

5.5

(4.3-9.4)

8.7

(7.2-13.7)




Conclusion: PFS as primary endpoint was not significantly different between arms. OS was significantly improved in the combination arm and was restricted to non squamous histology.