Renal Function Outcomes in Metastatic Non-Small-Cell Lung Carcinoma Patients Treated with Chemotherapy or Immune Checkpoint Inhibitors: An Unexpected Scenario
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Methods
2.2. Inclusion Criteria
2.3. Data Collection
2.4. Outcomes
2.5. Statistical Analysis
3. Results
3.1. Baseline Population Characteristics
3.2. Primary Endpoint: AKI Incidence
3.3. Secondary Endpoint: eGFR Decay over Time
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [CrossRef] [PubMed]
- Duma, N.; Santana-Davila, R.; Molina, J.R. Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment. Mayo Clin. Proc. 2019, 94, 1623–1640. [Google Scholar] [CrossRef] [PubMed]
- Planchard, D.; Popat, S.; Kerr, K.; Novello, S.; Smit, E.F.; Faivre-Finn, C.; Mok, T.S.; Reck, M.; Van Schil, P.E.; Hellmann, M.D.; et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2018, 29, iv192–iv237. [Google Scholar] [CrossRef] [PubMed]
- Gandhi, L.; Rodríguez-Abreu, D.; Gadgeel, S.; Esteban, E.; Felip, E.; De Angelis, F.; Domine, M.; Clingan, P.; Hochmair, M.J.; Powell, S.F.; et al. Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer. N. Engl. J. Med. 2018, 378, 2078–2092. [Google Scholar] [CrossRef]
- West, H.; McCleod, M.; Hussein, M.; Morabito, A.; Rittmeyer, A.; Conter, H.J.; Kopp, H.-G.; Daniel, D.; McCune, S.; Mekhail, T.; et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): A multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019, 20, 924–937. [Google Scholar] [CrossRef]
- Paz-Ares, L.; Luft, A.; Vicente, D.; Tafreshi, A.; Gümüş, M.; Mazières, J.; Hermes, B.; Çay Şenler, F.; Csőszi, T.; Fülöp, A.; et al. Pembrolizumab plus Chemotherapy for Squamous Non–Small-Cell Lung Cancer. N. Engl. J. Med. 2018, 379, 2040–2051. [Google Scholar] [CrossRef]
- Zhou, Y.; Lin, Z.; Zhang, X.; Chen, C.; Zhao, H.; Hong, S.; Zhang, L. First-line treatment for patients with advanced non-small cell lung carcinoma and high PD-L1 expression: Pembrolizumab or pembrolizumab plus chemotherapy. J. Immunother. Cancer 2019, 7, 120. [Google Scholar] [CrossRef] [Green Version]
- Herrmann, S.M.; Perazella, M.A. Immune Checkpoint Inhibitors and Immune-Related Adverse Renal Events. Kidney Int. Rep. 2020, 5, 1139–1148. [Google Scholar] [CrossRef]
- Cortazar, F.B.; Marrone, K.A.; Troxell, M.L.; Ralto, K.M.; Hoenig, M.P.; Brahmer, J.R.; Le, D.T.; Lipson, E.J.; Glezerman, I.G.; Wolchok, J.; et al. Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors. Kidney Int. 2016, 90, 638–647. [Google Scholar] [CrossRef] [Green Version]
- Perazella, M.A.; Shirali, A.C. Immune checkpoint inhibitor nephrotoxicity: What do we know and what should we do? Kidney Int. 2020, 97, 62–67. [Google Scholar] [CrossRef]
- Sury, K.; Perazella, M.A. The nephrotoxicity of new immunotherapies. Expert Rev. Clin. Pharmacol. 2019, 12, 513–521. [Google Scholar] [CrossRef] [PubMed]
- Aldossary, S.A. Review on Pharmacology of Cisplatin: Clinical Use, Toxicity and Mechanism of Resistance of Cisplatin. Biomed. Pharmacol. J. 2019, 12, 7–15. [Google Scholar] [CrossRef]
- Crona, D.J.; Faso, A.; Nishijima, T.F.; McGraw, K.A.; Galsky, M.D.; Milowsky, M.I. A Systematic Review of Strategies to Prevent Cisplatin-Induced Nephrotoxicity. Oncol. 2017, 22, 609–619. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pabla, N.; Dong, Z. Cisplatin nephrotoxicity: Mechanisms and renoprotective strategies. Kidney Int. 2008, 73, 994–1007. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Malyszko, J.; Kozłowska, K.; Kozłowski, L.; Małyszko, J. Nephrotoxicity of anticancer treatment. Nephrol. Dial. Transplant. 2017, 32, 924–936. [Google Scholar] [CrossRef]
- Latcha, S.; Jaimes, E.A.; Patil, S.; Glezerman, I.G.; Mehta, S.; Flombaum, C.D. Long–Term Renal Outcomes after Cisplatin Treatment. Clin. J. Am. Soc. Nephrol. 2016, 11, 1173–1179. [Google Scholar] [CrossRef]
- Levey, A.S.; Stevens, L.A.; Schmid, C.H.; Zhang, Y.L.; Castro, A.F., III; Feldman, H.I.; Kusek, J.W.; Eggers, P.; Van Lente, F.; Greene, T.; et al. A New Equation to Estimate Glomerular Filtration Rate. Ann. Intern. Med. 2009, 150, 604–612. [Google Scholar] [CrossRef]
- Levey, A.S.; de Jong, P.E.; Coresh, J.; El Nahas, M.; Astor, B.C.; Matsushita, K.; Gansevoort, R.T.; Kasiske, B.L.; Eckardt, K.-U. The definition, classification, and prognosis of chronic kidney disease: A KDIGO Controversies Conference report. Kidney Int. 2011, 80, 17–28. [Google Scholar] [CrossRef] [Green Version]
- Khwaja, A. KDIGO Clinical Practice Guidelines for Acute Kidney Injury. Nephron Clin. Pract. 2012, 120, c179–c184. [Google Scholar] [CrossRef]
- Madias, N.E.; Harrington, J.T. Platinum nephrotoxicity. Am. J. Med. 1978, 65, 307–314. [Google Scholar] [CrossRef]
- Rozencweig, M.; Von Hoff, D.D.; Slavik, M.; Muggia, F.M. Cis diamminedichloroplatinum (II). A new anticancer drug. Ann. Intern. Med. 1977, 86, 803–812. [Google Scholar] [CrossRef] [PubMed]
- Hartmann, J.T.; Kollmannsberger, C.; Kanz, L.; Bokemeyer, C. Platinum organ toxicity and possible prevention in patients with testicular cancer. Int. J. Cancer 1999, 83, 866–869. [Google Scholar] [CrossRef]
- Gore, M.E.; Calvert, A.H.; Smith, I.E. High dose carboplatin in the treatment of lung cancer and mesotherlioma: A phase I dose escalation study. Eur. J. Cancer Clin. Oncol. 1987, 23, 1391–1397. [Google Scholar] [CrossRef]
- Smit, E.F.; Willemse, P.H.; Sleijfer, D.T.; Uges, D.R.; Postmus, P.E.; Meijer, S.; Terheggen, P.M.; Mulder, N.H.; De Vries, E.G. Continuous infusion carboplatin on a 21-day schedule: A phase I and pharmacokinetic study. J. Clin. Oncol. 1991, 9, 100–110. [Google Scholar] [CrossRef]
- Vasconcellos, V.F.; Marta, G.N.; Da Silva, E.M.; Gois, A.; De Castria, T.B.; Riera, R. Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer. Cochrane Database Syst. Rev. 2020, 1, CD009256. [Google Scholar] [CrossRef]
- National Cancer Institute. Comprehensive Cancer Information. Common Toxicity Criteria Version 2.0. Available online: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcv20_4-30-992.pdf (accessed on 1 November 2021).
- Seethapathy, H.; Zhao, S.; Chute, D.F.; Zubiri, L.; Oppong, Y.; Strohbehn, I.; Cortazar, F.B.; Leaf, D.E.; Mooradian, M.J.; Villani, A.-C.; et al. The Incidence, Causes, and Risk Factors of Acute Kidney Injury in Patients Receiving Immune Checkpoint Inhibitors. Clin. J. Am. Soc. Nephrol. 2019, 14, 1692–1700. [Google Scholar] [CrossRef]
- Trevisani, F.; Di Marco, F.; Capitanio, U.; Larcher, A.; Bettiga, A.; Dosio, F.; Ghidini, M.; Del Conte, G.; Vago, R.; Cinque, A.; et al. Renal Function Assessment Gap in Clinical Practice: An Awkward Truth. Kidney Blood Press. Res. 2020, 45, 166–179. [Google Scholar] [CrossRef]
- Kooijmans, E.C.; Bökenkamp, A.; Tjahjadi, N.S.; Tettero, J.M.; van Dulmen-den, E.B.; Van Der Pal, H.J.; Veening, M.A. Early and late adverse renal effects after potentially nephrotoxic treatment for childhood cancer. Cochrane Database Syst. Rev. 2019, 3, CD008944. [Google Scholar] [CrossRef]
- Skinner, R.; Parry, A.; Price, L.; Cole, M.; Craft, A.W.; Pearson, A.D. Persistent nephrotoxicity during 10-year follow-up after cisplatin or carboplatin treatment in childhood: Relevance of age and dose as risk factors. Eur. J. Cancer 2009, 45, 3213–3219. [Google Scholar] [CrossRef]
- Chute, D.F.; Zhao, S.; Strohbehn, I.A.; Rusibamayila, N.; Seethapathy, H.; Lee, M.; Zubiri, L.; Gupta, S.; Leaf, D.E.; Rahma, O.; et al. Incidence and Predictors of CKD and Estimated GFR Decline in Patients Receiving Immune Checkpoint Inhibitors. Am. J. Kidney Dis. 2021, 79, 134–137. [Google Scholar] [CrossRef]
- Trevisani, F.; Di Marco, F.; Raggi, D.; Bettiga, A.; Vago, R.; Larcher, A.; Cinque, A.; Salonia, A.; Briganti, A.; Capitanio, U.; et al. Renal function outcomes in patients with muscle-invasive bladder cancer treated with neoadjuvant pembrolizumab and radical cystectomy in the PURE-01 study. Int. J. Cancer 2021, 149, 186–190. [Google Scholar] [CrossRef] [PubMed]
CKD Categories | Category Range: eGFR (mL/min/1.73 m2) | Category Description | Risk of Progression with A1 | Risk of Progression with A2 | Risk of Progression with A3 |
---|---|---|---|---|---|
G1 | >90 with clinical, laboratory, imaging evidence of kidney disease | Normal or high | Low | Moderately increased | High |
G2 | 60–89 | Mildly decreased | Low | Moderately increased | High |
G3a | 45–59 | Mildly to moderately decreased | Moderately increased | High | Very high |
G3b | 30–44 | Moderately to severely decreased | High | Very high | Very high |
G4 | 15–29 | Severely decreased | Very high | Very high | Very high |
G5 | <15 | Kidney failure | Very high | Very high | Very high |
Carbo 25% (n = 73) | Cis 35% (n = 101) | ICIs 40% (n = 118) | Total (n = 292) | p Value | |
---|---|---|---|---|---|
Treatment cycles Median (Q1, Q3) | 3.0 (2.0, 4.0) | 4.0 (2.0, 4.0) | 7.0 (4.0, 12.0) | 4.0 (2.0, 7.0) | <0.001 1 |
Mean follow-up time (days) | 67 | 84 | 143 | 104 | <0.001 1 |
Age, Median (Q1, Q3) | 72.0 (67.0, 77.0) | 66.0 (59.0, 74.0) | 72.0 (66.2, 77.0) | 70.5 (63.0, 76.0) | <0.001 1 |
Sex | 0.548 2 | ||||
Women | 23 (31.5%) | 30 (29.7%) | 43 (36.4%) | 96 (32.9%) | |
Men | 50 (68.5%) | 71 (70.3%) | 75 (63.6%) | 196 (67.1%) | |
Serum creatinine, Median (Q1, Q3) | 0.9 (0.8, 1.1) | 0.9 (0.7, 1.0) | 0.9 (0.7, 1.1) | 0.9 (0.8, 1.1) | 0.180 1 |
eGFR, Median (Q1, Q3) | 74.7 (64.7, 87.9) | 81.2 (72.3, 94.1) | 76.6 (61.8, 89.7) | 79.0 (65.7, 91.0) | 0.006 1 |
BMI, Median (Q1, Q3) | 23.7 (21.6, 26.7) | 23.1 (21.8, 25.5) | 24.2 (21.3, 26.9) | 23.6 (21.8, 26.4) | 0.454 1 |
Diabetes mellitus | 1 (14.3%) | 5 (16.1%) | 3 (10.3%) | 9 (13.4%) | 0.804 2 |
Hypertension | 14 (19.2%) | 26 (25.7%) | 35 (29.7%) | 75 (25.7%) | 0.273 2 |
CKD at baseline. Proportion of patients according to CKD G categories | 0.002 2 | ||||
CKD G1 | 15 (20.5%) | 34 (33.7%) | 28 (23.7%) | 77 (26.4%) | |
CKD G2 | 40 (54.8%) | 59 (58.4%) | 63 (53.4%) | 162 (55.5%) | |
CKD G3a | 9 (12.3%) | 8 (7.9%) | 22 (18.6%) | 39 (13.4%) | |
CKD G3b | 8 (11.0%) | 0 (0.0%) | 3 (2.5%) | 11 (3.8%) | |
CKD G4 | 1 (1.4%) | 0 (0.0%) | 2 (1.7%) | 3 (1.0%) | |
Institution | 0.002 2 | ||||
Cagliari | 7 (9.6%) | 31 (30.7%) | 29 (24.6%) | 67 (22.9%) | |
Milan | 36 (49.3%) | 38 (37.6%) | 63 (53.4%) | 137 (46.9%) | |
Rome | 30 (41.1%) | 32 (31.7%) | 26 (22.0%) | 88 (30.1%) |
Carbo 25% (n = 73) | Cis 35% (n = 101) | ICIs 40% (n = 118) | Total (n = 292) | p Value | |
---|---|---|---|---|---|
AKI | 5 (6.8%) | 11 (10.9%) | 10 (8.5%) | 26 (8.9%) | 0.638 1 |
Median eGFR decay at the end of follow up (mL/min) | 1.1 (−6.4;7.4) | 2.3 (−6; 14.6) | 2.6 (−3.5; 8.4) | 2.2 (−4.7; 10.1) | 0.7 2 |
ODDs Ratio | CI (0.95%) | p-Value | |
---|---|---|---|
Treatment: Immunotherapy 1 | 2.4 × 107 | 1.1 × 10−125; Inf | 1 |
Treatment: Cisplatin 1 | 5.5 × 107 | 2.4 × 10−152; Inf | 1 |
Basal eGFR | 1.1 | 1.0; 1.2 | 0.05 |
Hypertension | 1.0 | 1.2 × 10−1; 1.0 × 10 | 0.9 |
Diabetes | 1.2 | 4.0 × 10−2; 1.9 × 10 | 1 |
25 ≤ BMI < 30 | 1.5 | 6.3 × 10−2; 2.1 × 10 | 0.7 |
BMI ≥ 30 | 3.1 × 10−7 | 0; 1.7 × 10196 | 0.5 |
Beta (mL/min) | CI (0.95%) | p-Value | |
---|---|---|---|
Treatment: Immunotherapy 1 | −2 | −13; 8 | 0.6 |
Treatment: Cis-Platin 1 | −3 | −13; 7 | 0.6 |
Basal eGFR > 60 | 5 | −3; 13 | 0.2 |
Hypertension | −6 | −12; 0.3 | 0.06 |
Diabetes | 7 | −0.8; 16 | 0.07 |
BMI | 1 | −0.2; 1 | 0.2 |
AKI onset | 31 | 22; 40 | <0.001 |
Gender: Male | −3 | −9; 3 | 0.3 |
Total number of cycles | −0.04 | −1; 1 | 0.9 |
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Trevisani, F.; Di Marco, F.; Floris, M.; Pani, A.; Minnei, R.; Scartozzi, M.; Cirillo, A.; Gelibter, A.; Botticelli, A.; Rijavec, E.; et al. Renal Function Outcomes in Metastatic Non-Small-Cell Lung Carcinoma Patients Treated with Chemotherapy or Immune Checkpoint Inhibitors: An Unexpected Scenario. Vaccines 2022, 10, 679. https://doi.org/10.3390/vaccines10050679
Trevisani F, Di Marco F, Floris M, Pani A, Minnei R, Scartozzi M, Cirillo A, Gelibter A, Botticelli A, Rijavec E, et al. Renal Function Outcomes in Metastatic Non-Small-Cell Lung Carcinoma Patients Treated with Chemotherapy or Immune Checkpoint Inhibitors: An Unexpected Scenario. Vaccines. 2022; 10(5):679. https://doi.org/10.3390/vaccines10050679
Chicago/Turabian StyleTrevisani, Francesco, Federico Di Marco, Matteo Floris, Antonello Pani, Roberto Minnei, Mario Scartozzi, Alessio Cirillo, Alain Gelibter, Andrea Botticelli, Erika Rijavec, and et al. 2022. "Renal Function Outcomes in Metastatic Non-Small-Cell Lung Carcinoma Patients Treated with Chemotherapy or Immune Checkpoint Inhibitors: An Unexpected Scenario" Vaccines 10, no. 5: 679. https://doi.org/10.3390/vaccines10050679