1211 - Phase II single-arm study of preoperative pemetrexed (P) plus cisplatin (C) in non-small cell lung cancer (NSCLC) patients

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Anticancer agents
Non-small-cell lung cancer
Therapy
Biological therapy
Presenter Mariusz Chabowski
Authors M. Chabowski1, R. Ramlau2, W. Dyszkiewicz3, N. Chouaki4, V. Soldatenkova5, R. Varea6, S. Barriga6, C.M. Visseren-Grul7, T. Orlowski8
  • 1Department Of Surgery, 4th Military Academic Hospital in Wroclaw, 50-981 - Wroclaw/PL
  • 2Poznan University of Medical Sciences, 61-701 - Poznan/PL
  • 3Pneumology, Poznan University of Medical Sciences, 61-701 - Poznan/PL
  • 4Medical Department, Eli Lilly, Paris/FR
  • 5Medical Department, Eli Lilly, Bad Homburg/DE
  • 6Medical Department, Eli Lilly, Madrid/ES
  • 7Medical, Eli Lilly, RA Houten/NL
  • 8Clinic Of Surgery, National Tuberculosis and Lung Disease Research Institute, 01-138 - Warsaw/PL

Abstract

Early-stage NSCLC is potentially curable but many patients (pts) develop recurrent disease. Identification of markers (M) to predict tumor response (R), risk of recurrence and survival is critical. This phase II study in pts with operable, stage IB-IIIA NSCLC aimed to correlate expression of M with R to P/C in neoadjuvant setting (NS), and to characterize toxicity. P/C 500/75 mg/m2d1q3w up to 3 cycles was followed by radical surgery (S). Primary objective (PO) was to characterize and compare responders vs non-responders in terms of expression of molecular M in tumor tissue (DHFR, DPD, FPGS, RFC, alpha FR, TS, GARFT, EGFR, ERCC1, FPGH) and presence of hypermethylated genes in peripheral blood (RASSF1A, RAR-beta, p16). Secondary objectives included R rate, duration of R (DR), disease-free survival (DFS), overall survival (OS) and toxicity. From 05/2005 to 10/2008, 30/60 planned pts were enrolled. The study was terminated early due to slow recruitment and the P label restriction to non-squamous (nsq) NSCLC in 2008 based on evidence that nsq histology is a predictive M for P efficacy. Pt characteristics: median age 56 yrs, all Caucasian, 29 male, stage IB/IIA/IIB 18/2/10, histology adeno/squamous/not otherwise specified 2/20/8. Only few tumor samples were available, PO analyses were considered to be of little scientific relevance and not performed. Secondary efficacy analyses included 29 pts (1 pt had no measurable disease): median DFS was 43.7 months (mo), median OS not reached. Complete R/partial R/stable disease/progressive disease (CR/PR/SD/PD) was seen in 1/9/17/2 pts. R rate (CR + PR) was 34.5%. For 10 responders, median DR was 42.5 mo. The table gives safety overview for all 30 pts. No pts died on treatment (Tx). PO analyses were not conducted due to insufficient tumor sample availability and lack of scientific value. P/C in NS was well tolerated, in line with current safety data.

Overview of Adverse Events

Possibly Drug Related / Regardless of Drug Causality (N = 30)
# pts who died within 30 days of Tx* discontinuation 0/1
# pts with at least 1 Tx emergent AE (TEAE) 5**/21
# pts who discontinued due to AE 0/1***
# pts with at least 1 serious AE (SAE) 0/4
Bronchopleural fistula 0/2 (grade 4 and 5)
Gastric ulcer 0/1(grade 3)
Postprocedural hemorrhage 0/1(grade 3)
*Tx = P/C followed by S
** only 1 pt experienced a grade 3 TEAE (renal failure) possibly drug related, all other drug-related TEAEs were grade 1-2
*** grade 3 SAE (gastric ulcer)

Disclosure

R. Ramlau: The author declares that he received payment for lectures as well as for congress participation from Eli Lilly.

N. Chouaki: The author declares that she is fulltime employee of Eli Lilly and Company.

V. Soldatenkova: The author declares that she is fulltime employee of Eli Lilly and Company.

R. Varea: The author declares that she is a full-time employee of Eli Lilly and Company, and as such holds some Lilly stock.

S. Barriga: The author declares that she is fulltime employee of Eli Lilly and Company.

C.M. Visseren-Grul: The author declares that she is a full-time employee of Eli Lilly and Company, and as such holds some Lilly stock.

All other authors have declared no conflicts of interest.