1267P - A large retrospective analysis of pemetrexed (PEM) activity in patients (pts) with ALK-positive (ALK+) non-small cell lung cancer (NSCLC) prior to c...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Cytotoxic agents
Non-small-cell lung cancer
Biological therapy
Presenter Giorgio Scagliotti
Authors G. Scagliotti1, D.W. Kim2, A. Shaw3, S.I. Ou4, G.J. Riely5, S. Gettinger6, B. Besse7, K. Wilner8, Y. Tang8, C. Bartlett9
  • 1S. Luigi Hospital, University of Turin, Turin/IT
  • 2Department Of Internal Medicine, Seoul National University Hospital, Seoul/KR
  • 3Cancer Center, Massachusetts General Hospital, Boston/US
  • 4Cancer Centre, University of California at Irvine, Irvine/US
  • 5Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York/US
  • 6Thoracic Oncology Program, Yale University School of Medicine, CT - New Haven/US
  • 7Dept. Of Medicine, Institute Gustave Roussy, Villejuif/FR
  • 8Reseach And Development, Pfizer Oncology, La Jolla/US
  • 9Medical Oncology, Pfizer Oncology, New York/US



Retrospective small cohort studies evaluating multiple lines of therapy suggest ALK+ NSCLC may be particularly sensitive to PEM treatment.


PROFILE 1005 (NCT00932451; Pfizer) is a large phase 2 multinational, single-arm study of CRIZ in previously treated ALK+ NSCLC. We retrospectively assessed best overall response rate (ORR) and time to progression (TTP; 1st dose to objective progression) in pts who received PEM-based regimens prior to CRIZ in the 1st-line (1L) and 2nd-line (2L) settings. ORR to CRIZ post-PEM-based regimens was assessed.


Of the 901 ALK+ pts enrolled as of Jan 2012, 711 (79%) received prior PEM (single-agent or combination; any line advanced/metastatic) with an ORR to PEM of 19%. Pts who received 1L PEM combinations (n = 308) were predominately of young age (median 53 y, 82% <65 y), never/former smokers (96%), with good PS (82% ECOG <2) and had adenocarcinoma (95%). ORR to 1L PEM combinations was 24% (95% CI: 20, 29) and median TTP was 6.3 months (95% CI: 5.8, 7.0). These patients subsequently achieved higher ORR with ≥2L CRIZ (39%; 95% CI: 34, 45). Pts who received 2L single-agent PEM (n = 141) had similar demographic characteristics to those who received 1L PEM-based regimens (median age, 50 y; 84% <65 y; 95% never/former smokers; 82% ECOG <2; 93% adenocarcinoma). ORR to 2L single-agent PEM was 14% (95% CI: 9, 21) and median TTP was 5.4 months (95% CI: 4, 6.5). These patients subsequently achieved higher ORR with CRIZ in ≥3L (48%; 95% CI: 40, 57).


This retrospective analysis of a large data set reports lower ORR and shorter TTP with PEM than that reported in smaller retrospective cohorts of ALK+ NSCLC. This analysis and previous reports observed a tendency towards a higher ORR and/or better PFS or TTP with 1L and 2L PEM-based regimens in ALK+ NSCLC than in unselected populations, which may not be specifically related to ALK status but to clinical characteristics such as younger age, adenocarcinoma histology or a higher sensitivity to cytotoxic agents in never-smokers.


G. Scagliotti: Honoraria received from Pfizer, Eli Lilly, Roche and AstraZeneca.

D.W. Kim: Advisory relationship with Pfizer. Received honoraria from Pfizer.

A.T. Shaw: Advisory relationship with Pfizer, Ariad, Chugai, Novartis and Daiichi-sankyo. Received research funding from AstraZeneca and Novartis.

S.I. Ou: Advisory relationship with Pfizer and Genentech. Received honoraria from Pfizer, Genentech and Lilly. Received research funding from Pfizer.

G.J. Riely: Advisory relationship with Chugai, Ariad, Daiichi, Tragara, Foundation Medicine, Boehringer-Ingelheim and Novartis. Received research funding from Pfizer, Bristol-Myers Squibb, Chugai, GlaxoSmithKline, Novartis and Infinity.

B. Besse: Received research funding from Pfizer.

K. Wilner: Employed by Pfizer as a Senior Director and has stock ownership with Pfizer.

Y. Tang: Employed by Pfizer as a Manager and has stock ownership with Pfizer.

C.H. Bartlett: Employed by Pfizer as a Senior Director, Medical Affairs Lead and has stock ownership with Pfizer.

All other authors have declared no conflicts of interest.