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

Middleton, Gary;Gridelli, Cesare;De Marinis, Filippo;Pujol, Jean-Louis;Paz-Ares, Luis;et.al.
(2018) Current Medical Research and Opinion — Vol. 34, n° 5, p. 865-871 (2018)

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  • Middleton, Gary
    Author
  • Gridelli, Cesare
    Author
  • De Marinis, Filippo
    Author
  • Pujol, Jean-Louis
    Author
  • Pieters, ThierryUCLouvain
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  • Paz-Ares, Luis
    Author
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Abstract
OBJECTIVES: To assess the effect of long-term pemetrexed maintenance therapy on patients' renal function. METHODS: In the PARAMOUNT phase III trial (NCT 00789373), pemetrexed was compared with placebo as maintenance treatment in advanced nonsquamous non-small-cell lung cancer patients who completed 4 cycles of pemetrexed plus cisplatin induction therapy. To evaluate changes in renal function during pemetrexed continuation maintenance treatment, we retrospectively analyzed changes in serum creatinine (sCr), treatment-emergent adverse events, dose delays and treatment discontinuations associated with impaired renal function. RESULTS: Creatinine clearance ≥45 mL/min was required before the start of any cycle. Patients on pemetrexed maintenance had a significantly higher percentage maximum increase in sCr over baseline versus placebo for the range of ≥10% to ≥90% increase (p < .05). The risk of experiencing renal events leading to dose delays and discontinuations was higher with higher increases in sCr but reversible in most patients. sCr increases of ≥30% and ≥40% were associated with gender (female), age (<70 years) and longer exposure to pemetrexed compared with placebo. Sixteen (4%) pemetrexed patients and 1 (1%) placebo patient discontinued treatment due to drug-related renal events; 13/16 (81%) of those pemetrexed patients had sCr increases ≥30% and 7/13 (54%) had pre-existing conditions and/or were receiving nephrotoxic drugs. CONCLUSIONS: The appearance of renal events leading to dose delays and/or treatment discontinuations was associated with sCr increase of at least 30%. However, it was difficult to identify patients at a higher risk of treatment discontinuation due to a drug-related renal event based only on changes in pre-maintenance laboratory values.
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Middleton, G., Gridelli, C., De Marinis, F., Pujol, J.-L., Reck, M., Ramlau, R., Parente, B., Pieters, T., Visseren-Grul, C. M., San Antonio, B., John, W. J., Zimmermann, A. H., Chouaki, N., & Paz-Ares, L. (2018). Evaluation of changes in renal function in PARAMOUNT: a phase III study of maintenance pemetrexed plus best supportive care versus placebo plus best supportive care after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. Current Medical Research and Opinion, 34(5), 865-871. https://doi.org/10.1080/03007995.2018.1439462 (Original work published 2018)