Predictors of the response to nivolumab immunotherapy in the second or subsequent lines for metastatic non‑small cell lung cancers

Săftescu,Sorin; Negru,Șerban; Volovăț,Simona; Popovici,Dorel; Chercota,Vlad; Stanca,Simona; Feier,Horea; Malita,Daniel; Dragomir,Radu; Volovăț,Constantin

doi:10.3892/etm.2021.10037

Predictors of the response to nivolumab immunotherapy in the second or subsequent lines for metastatic non‑small cell lung cancers

Authors:
- Sorin Săftescu
- Șerban Negru
- Simona Volovăț
- Dorel Popovici
- Vlad Chercota
- Simona Stanca
- Horea Feier
- Daniel Malita
- Radu Dragomir
- Constantin Volovăț
View Affiliations

Affiliations: Department of Oncology, ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania, Department of Oncology, ‘Gr. T. Popa’ University of Medicine and Pharmacy, 700115 Iasi, Romania, Department of Ophthalmology, ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania, Department of Pediatrics, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania, Department of Cardiovascular Surgery, ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania, Department of Radiology and Medical Imaging, ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania, Department of Obstetrics and Gynecology, ‘Victor Babeș’ University of Medicine and Pharmacy, 300041 Timisoara, Romania
Published online on: April 14, 2021 https://doi.org/10.3892/etm.2021.10037
Article Number: 605
Copyright: © Săftescu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Checkpoint inhibitors represent the first therapeutic class to replace chemotherapy lines for the treatment of metastatic non‑small cell lung cancer (NSCLC), due to improved overall survival and tolerability. Nivolumab, a fully human anti‑programmed cell death‑1 immunoglobulin G4 monoclonal antibody, is the first immune checkpoint inhibitor approved by the US Food and Drug Administration in 2014 for cases of metastatic melanoma and in 2015 for cases of squamous cell lung cancer and kidney cell cancer. The present study aimed to identify predictive markers (favorable or unfavorable) for time to treatment discontinuation using nivolumab in the second or subsequent line of therapy of metastatic NSCLC cases. Analysis of a group of 78 NSCLC patients treated with nivolumab allowed the identification of negative predictive markers, related to the presence of metastases (adrenal in men under 65 years, liver, brain and the number of metastatic sites) and the hematological profile (neutrophilia at the initiation of treatment and lymphocyte variation at 6 weeks of treatment).

View Figures

View References

1	Pardoll DM: The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 12:252–264. 2012.PubMed/NCBI View Article : Google Scholar
2	Niezgoda A, Niezgoda P and Czajkowski R: Novel approaches to treatment of advanced melanoma: A review on targeted therapy and immunotherapy. Biomed Res Int. 2015(851387)2015.PubMed/NCBI View Article : Google Scholar
3	Bansal P, Osman D, Gan GN, Simon GR and Boumber Y: Recent advances in immunotherapy in metastatic NSCLC. Front Oncol. 6(239)2016.PubMed/NCBI View Article : Google Scholar
4	Gill DM, Agarwal N and Vaishampayan U: Evolving treatment paradigm in metastatic renal cell carcinoma. Am Soc Clin Oncol Educ Book. 37:319–329. 2017.PubMed/NCBI View Article : Google Scholar
5	Wang C, Thudium KB, Han M, Wang XT, Huang H, Feingersh D, Garcia C, Wu Y, Kuhne M, Srinivasan M, et al: In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res. 2:846–856. 2014.PubMed/NCBI View Article : Google Scholar
6	Renner A, Burotto M and Rojas C: Immune checkpoint inhibitor dosing: Can we go lower without compromising clinical efficacy? J Glob Oncol. 5:1–5. 2019.PubMed/NCBI View Article : Google Scholar
7	Agrawal S, Feng Y, Roy A, Kollia G and Lestini B: Nivolumab dose selection: Challenges, opportunities, and lessons learned for cancer immunotherapy. J Immunother Cancer. 4(72)2016.PubMed/NCBI View Article : Google Scholar
8	Yoo SH, Keam B, Kim M, Kim SH, Kim YJ, Kim TM, Kim DW, Lee JS and Heo DS: Low-dose nivolumab can be effective in non-small cell lung cancer: Alternative option for financial toxicity. ESMO Open. 3(e000332)2018.PubMed/NCBI View Article : Google Scholar
9	Zhang J, Sanghavi K, Shen J, Zhao X, Feng Y, Statkevich P, Sheng J, Roy A and Zhu L: Population pharmacokinetics of nivolumab in combination with ipilimumab in patients with advanced malignancies. CPT Pharmacometrics Syst Pharmacol. 8:962–970. 2019.PubMed/NCBI View Article : Google Scholar
10	Cortellini A, Verna L, Porzio G, Bozzetti F, Palumbo P, Masciocchi C, Cannita K, Parisi A, Brocco D, Tinari N and Ficorella C: Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non-small cell lung cancer patients: A ‘hypothesis-generator’ preliminary report. Thorac Cancer. 10:347–351. 2019.PubMed/NCBI View Article : Google Scholar
11	Payne RB, Little AJ, Williams RB and Milner JR: Interpretation of serum calcium in patients with abnormal serum proteins. Br Med J. 4:643–646. 1973.PubMed/NCBI View Article : Google Scholar
12	Cusato J, Genova C, Tomasello C, Carrega P, Ottonello S, Pietra G, Mingari MC, Cossu I, Rijavec E, Leggieri A, et al: Influence of vitamin D in advanced non-small cell lung cancer patients treated with nivolumab. Cancers (Basel). 11(125)2019.PubMed/NCBI View Article : Google Scholar
13	Barta JA, Powell CA and Wisnivesky JP: Global epidemiology of lung cancer. Ann Glob Health. 85(8)2019.PubMed/NCBI View Article : Google Scholar
14	Tamura T, Kurishima K, Nakazawa K, Kagohashi K, Ishikawa H, Satoh H and Hizawa H: Specific organ metastases and survival in metastatic non-small-cell lung cancer. Mol Clin Oncol. 3:217–221. 2015.PubMed/NCBI View Article : Google Scholar
15	Crinò L, Bronte G, Bidoli P, Cravero P, Minenza E, Cortesi E, Garassino MC, Proto C, Cappuzzo F, Grossi F, et al: Nivolumab and brain metastases in patients with advanced non-squamous non-small cell lung cancer. Lung Cancer. 129:35–40. 2019.PubMed/NCBI View Article : Google Scholar
16	Karantanos T, Karanika S, Seth B and Gignac G: The absolute lymphocyte count can predict the overall survival of patients with non-small cell lung cancer on nivolumab: A clinical study. Clin Transl Oncol. 21:206–212. 2019.PubMed/NCBI View Article : Google Scholar
17	Pantano F, Russano M, Berruti A, Mansueto G, Migliorino MR, Adamo V, Aprile G, Gelibter A, Ficorella C, Falcone A, et al: Prognostic clinical factors in patients affected by non-small-cell lung cancer receiving nivolumab. Expert Opin Biol Ther. 20:319–326. 2020.PubMed/NCBI View Article : Google Scholar
18	Preda MA, Popa G, Karancsi OL, Musat O, Popescu SI, Munteanu M and Popa Z: Effectiveness of subconjunctival bevacizumab associated with a laser-based procedure in the treatment of neovascular glaucoma. Farmacia. 66:621–626. 2018.
19	Boruga O, Balasoiu AT, Giuri S, Munteanu M, Stanca HT, Iovanescu G and Preda MA: Caruncular late-onset junctional nevus: Apropos of an anatomo-clinical observation. Rom J Morphol Embryol. 58:1461–1464. 2017.PubMed/NCBI
20	Preda MA, Karancsi OL, Munteanu M and Stanca HT: Clinical outcomes of micropulse transscleral cyclophotocoagulation in refractory glaucoma-18 months follow-up. Lasers Med Sci. 35:1487–1491. 2020.PubMed/NCBI View Article : Google Scholar
21	Stanca HT, Munteanu M, Jianu DC, Motoc AGM, Tăbăcaru B, Stanca S, Ungureanu E, Boruga VM and Preda MA: New perspectives in the use of laser diode transscleral cyclophotocoagulation. A prospective single center observational cohort study. Rom J Morphol Embryol. 59:869–872. 2018.PubMed/NCBI
22	Stanca HT, Petrović Z and Munteanu M: Transluminal Nd:YAG laser embolysis-a reasonable method to reperfuse occluded branch retinal arteries. Vojnosanit Pregl. 71:1072–1077. 2014.PubMed/NCBI View Article : Google Scholar
23	Lee CS, Devoe CE, Zhu X, Fishbein JS and Seetharamu N: Pretreatment nutritional status and response to checkpoint inhibitors in lung cancer. Lung Cancer Manag. 9(LMT31)2020.PubMed/NCBI View Article : Google Scholar