Patterns of renal toxicity from the combination of pemetrexed and pembrolizumab for advanced nonsquamous non-small-cell lung cancer (NSCLC): a single-center experience
Menée en Italie à partir de données portant sur 89 patients atteints d'un cancer du poumon non à petites cellules non épidermoïde de stade avancé, cette étude rétrospective analyse la survenue et les caractéristiques d'une insuffisance rénale aiguë en lien avec un traitement de première ligne combinant pembrolizumab et pémétrexed
Objectives : The combination of immune-checkpoint inhibitors (ICI) and platinum-pemetrexed chemotherapy(CT) in first-line setting improved survival outcomes of advanced non-small cell lungcancer (NSCLC) patients. Among the various adverse events, renal toxicity can be arelevant safety issue. Materials and methods : We conducted a single-center, observational retrospective study including consecutivepatients treated with upfront CT-ICI for advanced nonsquamous NSCLC to investigateincidence and clinical characteristics of acute kidney injury (AKI) using ‘Acute KidneyInjury Working Group of Kidney Disease: Improving Global Outcomes’ (KDIGO) definition. Results : A total of 89 patients received a first-line CT/ICI. The median age was 69 years.60.7% were male, and 87.6% had an ECOG PS of 0-1. 92.1% had a baseline glomerularfiltration rate of at least 60 ml/min. According to KDIGO criteria, 25 (28%) patientsdeveloped AKI. Considering risk factors for AKI onset, patients receiving more than10 cycles of CT/ICI were more likely to experience AKI (p < 0.001). No other associationswere found with other variables, including concomitant medications. Any componentof the treatment was discontinued (pemetrexed pembrolizumab or both) was discontinuedin 10 (40%) patients, and 9 patients (36 %) were addressed to nephrological consultation.These patients had higher mean creatinine variation from baseline (1 vs. 0.6 mg/dl,p = 0.025) and creatine level (1.8 vs. 1.4 mg/dl, p = 0.015), but lower eGFR (35.7vs. 54.2 ml/min, p = 0.011) in comparison to patients not addressed. No patients hadmicroscopic hematuria or pyuria, but mild proteinuria (< 0.8 g/24 h) was found in4 patients. A renal biopsy was performed on 3 patients, revealing acute tubule interstitialnephritis (ATIN), karyomegalic interstitial nephritis, and acute tubular necrosis(ATN). Conclusion : Renal toxicity represents a challenging adverse event that could negatively impactoutcomes of metastatic nonsquamous NSCLC patients receiving CT/ICI demanding a multidisciplinaryapproach.
Lung Cancer 2022