Renal Adverse Events Associated with Atezolizumab Plus Bevacizumab, Carboplatin, and Paclitaxel (ABCP) Therapy in Patients with Non-small Cell Lung Cancer

Background: In recent years, the combination therapy comprising immune checkpoint inhibitors (ICIs), VEGF inhibitors, and cytotoxic anticancer drugs has gained prominence in treating various advanced cancers. ICIs, notably, can induce immune-related adverse events (irAEs) like acute interstitial nephritis (AIN), while VEGF inhibitors are associated with proteinuria, occasionally manifesting as nephrotic syndrome (NS). A novel regimen, ABCP therapy (atezolizumab + bevacizumab + carboplatin + paclitaxel), has emerged for non-small cell lung cancer. In the global phase III IMpower150 study of ABCP, renal adverse events included NS in 2.5%, severe AKI in 0.3%, and AIN due to irAE in 0.8%. This study aims to assess renal adverse events in such patients treated with ABCP at our institution, examining their clinical characteristics and risk factors. Methods: We conducted a study involving 73 non-small cell lung cancer patients treated with ABCP therapy (up to 4 cycles of ABCP, followed by continuation of atezolizumab + bevacizumab combination therapy). We evaluated the incidence of nephrotic-level proteinuria and AKI. Results: At the initiation of ABCP therapy, the median age was 70 years (IQR 64.5 - 73), UPCR was 0.11 g/gCr (IQR 0.07 - 0.16), and eGFR was 73.1 ml/min/1.73m2 (IQR 58.4 - 87). Patients underwent a median of 6 cycles of ABCP (IQR 2.3 - 11), with a median observation period of 10 months (IQR 5.5 - 15). Notably, 4 patients (5.5%) exhibited UPCR ≥3.5 g/gCr, and 1 patient (1.4%) experienced AKI due to irAE, necessitating steroid treatment. Patients with nephrotic-level proteinuria tended to have higher UPCR at treatment onset (0.24; 0.1- 0.38) vs (0.11; 0.07 - 0.15), lower BMI (18;17.3 - 20.1) vs (21.2; 19.2 - 24.2), and more frequent ABCP therapy sessions (10; 8.3 - 26.8) vs (6; 2 - 10.8) compared to those without. Conclusion: The incidence of massive proteinuria may be higher during ABCP therapy in real-world clinical practice compared to the phase III trial. Possible contributing factors include patients with elevated UPCR prior to treatment initiation, potential excessive bevacizumab doses in patients with progressive emaciation, and the prolonged duration of ABCP treatment.