1257P - Evaluation of changes in renal function in a phase III study of maintenance (mtc) pemetrexed (pem) plus best supportive care (BSC) versus placebo (...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Supportive Care
Non-Small-Cell Lung Cancer, Metastatic
Presenter Gary Middleton
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors G. Middleton1, C. Gridelli2, F. De Marinis3, J. Pujol4, M. Reck5, R. Ramlau6, M.B. Parente7, T. Pieters8, C.M. Visseren-Grul9, B. San Antonio10, W. John11, A. Zimmermann11, N. Chouaki12, L. Paz-Ares13
  • 1Medical Oncology, University of Birmingham, B15 2TT - Birmingham/GB
  • 2Medical Oncology, UO Oncologia Medica"S.G. Moscati Hospital", IT-83100 - Avellino/IT
  • 3Thoracic Oncology Division, European Institute of Oncology, Milan/IT
  • 4Oncology, Montpellier Academic Hospital, Hospital Arnaud De Villeneuve, Montpellier, 34295 - Montpellier/FR
  • 5Department Of Thoracic Oncology, Lung Clinic Grosshansdorf, Grosshansdorf/DE
  • 6Lung Diseases Center, Poznan University of Medical Sciences, PL-60-569 - Poznan/PL
  • 7Pneumology, Centro Hospitalar de Vila Nova de Gaia/Espinho (CHVNG/E), Gaia/PT
  • 8Pulmonology, Cliniques Universitaires St. Luc, Brussels/BE
  • 9Medical, Lilly Oncology Europe, 3583 HR - Utrecht/NL
  • 10Oncology, Eli Lilly and Company, Madrid/ES
  • 11Oncology, Eli Lilly and Company, Indianapolis/US
  • 12Oncology-thoracic, Eli Lilly and Company, Paris/FR
  • 13Oncology, Seville University Hospital, Seville/ES

Abstract

Aim

Events associated with decreased renal function are reported in ≥1% and <10% of patients (pts) receiving pem, but the impact of long-term pem mtc tx on serum creatinine (sCr) and its correlation with the appearance of clinically relevant renal events leading to dose delays and tx discontinuations (dc) have not been evaluated.

Methods

To evaluate changes in renal function during pem continuation mtc tx, we retrospectively analyzed changes in sCr using centralized lab values. Treatment-emergent adverse events (TEAEs), dose delays, and tx dcs associated with impaired renal function were also examined.

Results

Creatinine clearance ≥45 mL/min was required before the start of any cycle. Pts on pem mtc had a significantly higher % maximum (max) increase (incr) in sCr over baseline vs plb for the range of ≥10% to ≥90% incr (P < .05) (Table). More female pts experienced sCr incr than males in both arms. 40% of plb pts with sCr incr ≥30% had it within first 2 cycles vs 10% of pem pts. Sixteen (4%) pem pts and 1 (1%) plb pt dc due to drug-related renal events; of those, 14 (82%) had sCr incr ≥30%. Of 12 pem pts with a mtc dose delay associated with a renal event and a sCr incr ≥30%, 7 pts (58%) recovered (renal event ended) and 4 pts (33%) eventually discontinued.

Max sCr incr over baseline, % Pem Pts w/ sCr incr, % Pem Pts w/ ≥1 renal TEAE, % Plb Pts with sCr incr, % Plb Pts w/ ≥1 renal TEAE, %
≥10 68 8 51 4
≥20 47 8 28 3
≥30 33 7 15 2
≥40 22 5 6 1
≥50 14 4 4 1
≥60 9 3 2 1
≥70 8 3 2 1

a The majority of pts with ≥1 renal TEAE had a dose delay or dc associated with a renal event. b Randomized to: Pem N = 359; Plb = 180. c P < .05 for sCr incr for listed between-arm comparisons.

Conclusions

During extended pem mtc tx, the appearance of clinically relevant renal events leading to dose delays and/or dcs (4% dc in pem arm) was generally associated with % incr in sCr, but was reversible in many pts . The higher the incr in sCr, the higher the risk of dc due to a drug-related renal event. sCr incr was associated with gender and longer exposure to pem.

Disclosure

G. Middleton: I have a compensated advisory role with Eli Lilly and Company; C. Gridelli: I have a compensated consultant/advisory role for Eli Lilly and Company and Roche. I have received honoraria from both for presentations. I have received research support from Eli Lilly and Company; M. Reck: I have a consultant/advisory role for Eli Lilly, Hoffman-LaRoche, BMS, Pfizer, Astra Zeneca and Boehringer-Ingelheim. I have received honoraria from all for presentations; R. Ramlau: I have a compensated consultant or advisory role with Eli Lilly and Company, and I have received honoraria from Eli Lilly for presentations; T. Pieters: I act as a compensated consultant for Eli Lilly and Company. I have received honoraria for presentations; C.M. Visseren-Grul: I am a compensated employee of Eli Lilly and Company, and I own stock in Eli Lilly and Company; B. San Antonio: I am a compensated employee of Eli Lilly and Company; W. John: William John is a compensated employee of Eli Lilly and Company and owns stock in the company; A. Zimmermann: I am a compensated employee of Eli Lilly and Company, and I own stock in Eli Lilly and Company; N. Chouaki: I am a compensated employee of Eli Lilly and Company, and I own stock in the company; L. Paz-Ares: I have received honoraria from Eli Lilly and Company for presentations. All other authors have declared no conflicts of interest.