Nivolumab in real-life clinical practice

Purpose of the study. To evaluate the efficacy and tolerability of nivolumab in oncologic patients in real-life clinical seffings.

Patients and methods. Analysis included 114 patients aged 26-96 years with melanoma (n = 64), non-small cell lung carcinoma (NSCLC) (n = 37) and metastatic colorectal cancer with high levels of microsatellite instability (MSI-H mCRC) (n = 13), receiving immune checkpoint therapy with nivolumab (3 mg/kg every 14 days). All patients underwent comprehensive examination including CT/chest radiography, CT/MRI/ultrasound of abdominal organs or PET-CT of the whole body and other investigations if necessary. Efficacy of treatment was assessed after every 6 courses on treatment or in case of signs of clinical progression. Treatment response was assessed using iRECIST 1.1 criteria.

Results. Among patients with metastatic melanoma positive for BRAF gene mutation, receiving immune therapy objective treatment response was registered in 13.6%, tumor control — in 27.2%. In the group of patients, negative for BRAF gene mutation objective response was achieved in 27.5%, tumor control — in 41.4% patients. None of mCRC patients in our group achieved objective response, stable disease was observed in 30.8% of patients, progression — in 38.5% and unconfirmed progression — in 7.7% of patients. In NSCLC group complete response was observed in 2.7%, partial response — in 2.7%, stabilization — in 27.1%, unconfirmed progression — in 5.4%, progression — in 29.7% of patients. Safety analysis revealed the following significant adverse reactions: thyroiditis (n = 3), pneumonitis of 3 grade (n = 1), hepatitis of 3 grade (n = 1) and arthritis of 2 grade (n = 1). In 4 patients adverse reactions required treatment delay and prescription of glucocorticoids.

Conclusion. Nivolumab treatment in real-life clinical practice is associated with a lower prevalence of adverse events compared to the results of clinical trials.

1. Amarnath S, Mangus CW, Wang JC, Wei F, He A, Kapoor V, et al. The PDL1-PD1 axis converts human TH1 cells into regulatory T cells. Sci Transl Med. 2011 Nov 30; 3(m):U1ra120. DOI: 10.1126/scitranslmed.3003130

2. Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, et al. Survival, durable tumor remission, and longterm safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014 April 1; 32(10):1020-1030. DOI: 10.1200/JCO.2013.53.0105

3. Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, et al. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Jun 22; 376 (25):2415—2426. DOI: 10.1056/NEJMoa1613493

4. Smith KM, Desai J. Nivolumab for the treatment of colorectal cancer. Journal Expert Review of Anticancer Therapy. 2018 Jul; 18(7):611—618. DOI: 10.1080/14737140.2018.1480942

5. Malhotra J, Jabbour SK, Aisner J. Current state of immunotherapy for non-small cell lung cancer. Transl Lung Cancer Res. 2017 Apr; 6(2):196—211. DOI: 10.21037/tlcr.2017.03.01

6. Ricciuti B, Genova C, Bassanelli M, De Giglio A, Brambilla M, Metro G, et al. Safety and Efficacy of Nivolumab in Patients With Advanced Non-small-cell Lung Cancer Treated Beyond Progression. Clin Lung Cancer. 2019 May 19; 20(3):178-185.e2. DOI: 10.1016/j.cllc.2019.02.001

7. Topalian SL, Hodi FS, Brahmer JR, Geffinger SN, Smith DC, McDermott DF, et al. Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer. N Engl J Med. 2012 Jun 28; 366 (26):2443—2454. DOI: 10.1056/NEJMoa1200690

8. Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in Previously Untreated Melanoma without BRAF. N Engl J Med. 2015 Jan 22; 372(4):320-330. DOI: 10.1056/NEJMoa1412082

9. Geffinger SN, Horn L, Gandhi L, Spigel DR, Antonia SJ, Riz- vi NA, et al. Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2015 Jun 20; 33(18):2004-2012. DOI: 10.1200/JC0.2014.58.3708

10. Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015 May 21; 372 (21):2006—2017. DOI: 10.1056/NEJMoa1414428

11. Rounds A, Kolesar J. Nivolumab for second-line treatment of metastatic squamous non-small-cell lung cancer. Am J Health Syst Pharm. 2015 Nov 1;72(21):1851-1855. DOI: 10.2146/ajhp150235

12. Sundar R, Cho BC, Brahmer JR, Soo RA. Nivolumab in NS-CLC: latest evidence and clinical potential. Ther Adv Med Oncol. 2015 Mar; 7(2):85-96. DOI: 10.1177/1758834014567470

13. Kirkwood JM, Butterfield LH, Tarhini AA, Zarour H, Kalinski P, Ferrone S. Immunotherapy of cancer in 2012. CA Cancer J Clin. 2012 Sep-Oct; 62(5):309-335. DOI: 10.3322/caac.20132

14. Ledford H. Cancer treatment: The killer within. Nature. 2014 Apr 3; 508 (7494):24-26. DOI: 10.1038/508024a

15. Topalian SL, Weiner GJ, Pardoll DM. Cancer immunotherapy comes of age. J Clin Oncol. 2011 Dec 20; 29(36):4828-4836. DOI: 10.1200/JCO.2011.38.0899

16. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28; 366(26):2455- 2465. DOI: 10.1056/NEJMoa1200694

17. Larkin J, Minor D, D'Angelo S, Neyns B, Smylie M, Miller WH Jr, et al. Overall Survival in Patients With Advanced Melanoma Who Received Nivolumab Versus Investigator's Choice Chemotherapy in CheckMate 037: A Randomized, Controlled, Open-Label Phase III Trial. J Clin Oncol. 2018; 36(4):383-390. DOI: 10.1200/JCO.2016.71.8023

18. Reck M, Brahmer J, Bennett B, Taylor F, Penrod JR, DeRosa M, et al. Evaluation of health-related quality of life and symptoms in patients with advanced non-squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 057. Eur J Cancer. 2018; 102:23-30. DOI: 10.1016/j.ejca.2018.05.005

19. Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18(9):1182-1191. DOI: 10.1016/S1470-2045(17)30422-9