Evaluation of changes in renal function in a phase III study of maintenance Pemetrexed plus best supportive care (BSC) versus placebo plus BSC after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer (PARAMOUNT)

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.