1233P - Safety data analyses for first-line pemetrexed plus carboplatin (Pem + Cb) in nonsquamous non-small cell lung cancer (ns-NSCLC)

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Non-Small Cell Lung Cancer
Biological Therapy
Presenter Isamu Okamoto
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors I. Okamoto1, W. Schuette2, T. Stinchecombe3, J. Rodrigues Pereira4, J. Liu5, B. San Antonio6, W. John5, J. Chen5, R. Zinner7
  • 1Center For Clinical And Translational Research, Kyushu University Hospital, 812-8582 - Fukuoka/JP
  • 2Dept Of Internal Medicine Ii, Hospital Martha-Maria, Halle-Dolau, Halle/DE
  • 3Department Of Medicine, University of North Carolina, Chapel Hill/US
  • 4Lung Cancer Division, Institute of Cancer Arnaldo Vieira de Carvalho, Sao Paolo/BR
  • 5Oncology, Eli Lilly and Company, Indianapolis/US
  • 6Oncology, Eli Lilly and Company, Madrid/ES
  • 7Md Anderson Cancer Center, University of Texas, Houston/US



The safety profiles of Pem + Cb for the two Cb doses (area under the curve [AUC] 5 and 6 mg/ml•min) most widely used in clinical practice have not been compared in the clinical-trial setting.


A total of 486 patients (pts) with advanced ns-NSCLC were identified from the safety populations of 5 historical phase II-IV Lilly-sponsored trials of first-line Pem + Cb (Cb: AUC 5, 105 pts [22%]/1 trial; AUC 6, 381 pts [78%]/4 trials). Pts received Pem + Cb for up to 4 or 6 cycles. The primary objective was to compare the safety profiles (selected drug-related treatment-emergent adverse events [TEAEs]) of first-line Pem + Cb AUC 5 vs. AUC 6. The safety profiles between Cb doses were compared using frequency table analysis (FTA). The generalized linear mixed effect model (GLMM) and the propensity score (PS) method were also used to compare hematologic (hem) toxicity.


FTA comparison showed that Pem + Cb AUC 5 vs. Pem + Cb AUC 6 was associated with a statistically significant lower incidence of all-grade TEAEs including thrombocytopenia (20.0% vs. 57.0%), anemia (32.4% vs. 62.2%), fatigue (11.4% vs. 47.5%), and vomiting (15.2% vs. 25.2%), as well as a lower rate of grade 3/4 thrombocytopenia (11.4% vs. 29.1%) (all P <.05; Fisher's exact test). The incidence of all-grade neutropenia and grade 3/4 neutropenia, anemia, fatigue, and vomiting was numerically lower for Cb AUC 5. GLMM results revealed a numerically favorable, but not statistically significant, odds ratio (OR) for Cb AUC 5 vs. AUC 6 for all-grade and grade 3/4 hem TEAEs (OR <1; P > .05), except grade 3/4 leukopenia (OR >1). After 1:1 PS matching of pts in AUC groups (105 pts/group), FTA showed Pem + Cb AUC 5 vs. AUC 6 had significantly less all-grade and grade 3/4 hem TEAEs (P <.05), except grade 3/4 leukopenia. A PS regression adjustment revealed the Cb AUC 5 vs. AUC 6 group was less likely to experience all-grade hem TEAEs and grade 3/4 thrombocytopenia and anemia (all OR <1; all P <.05).


Overall, Pem + Cb AUC 5 showed a better safety profile than Pem + Cb AUC 6, which was consistent across three statistical approaches. Due to the heterogeneity of the trials analyzed, this trend should be confirmed in a randomized prospective trial.


T. Stinchecombe: I participated in and an advisory board for Lilly Oncology and I was paid as well as received food (estimated value <500$). I have received research funding related to participation in clinical trials supported by Lilly Oncology; J. Liu: I am the Lilly employes; B. San Antonio: I am a full-time Eli Lilly and Company employee; W. John: I am a paid employee of Eli Lilly and Co. I also own approximately 1000 shares of Lilly stock; J. Chen: I am an employee and stock holder of Eli Lilly and Company; R. Zinner: I am principle investigator on a recently completed Eli Lilly sponsored clinical study submitted for publication. All other authors have declared no conflicts of interest.