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nivolumab (Opdivo)

Indications: - treatment of renal cell carcinoma - urothelial carcinoma - locally advanced or metastatic urothelial carcinoma during or following platinum-containing chemotherapy - adjuvant nivolumab after radical surgery - FDA-approved as adjuvant therapy regardless of prior neoadjuvant chemotherapy, nodal involvement, or PD-L1 status - metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy [2] - FDA-approved regardless of PD-L1 expression [6] - in combination with chemotherapy for neoadjuvant treatment of NSCLC [14] - treatment of cutaneous melanoma in combination with ipilimumab [3] - alone better than ipilimumab for resected cutaneous melanoma & less toxic (both drugs made by Bristol-Myers Squibb) [8] - refractory Hodgkin's lymphoma - hepatocellular carcinoma previously treated with sorafenib - refractory metastatic colorectal cancer with microsatellite instability or mismatch repair deficiency - neoadjuvant chemotherapy for Merkel cell carcinoma [12] - adjuvant therapy for resected esophageal cancer [13,15] - adjuvant therapy for resected gastroesophageal junction cancer [13,15] - in combination with ipilimumab (Yervoy) for neoadjuvant treatment of colorectal adenocarcinoma with mismatch repair deficiency [19] Benefit/risk: - extends median overall survival by 3 months in patients with non-small cell lung cancer compared with docetaxel (12.2 vs 9.4 months) [2]* - a subset of patients with high PD-L1 expression showed even greater benefit, median overall survival 17-19 months [2]* * study (CheckMate study) funded by Bristol-Myers Squibb Dosage: - 3 mg/lg every 2 weeks beun 4 weeks prior to surgery [10] Adverse effects: - most common - fatigue - dyspnea - musculoskeletal pain - anorexia - cough - nausea - constipation - immunosuppression-related effects [2] - may increase risk of autoimmune disease [7] - colitis, diarrhea most commonly in association with ipilimumab - inflammatory arthritis & sicca syndrome induced by nivolumab & ipilimumab [7] - treatment-related deaths due to pneumonitis [16] Toxicity: - discontinue nivolumab - high-dose intravenous glucocorticoids [5] - methylprednisolone Mechanism of action: - blocks ligand activation of programmed cell death-1 receptor (PD-1 receptor) on activated T cells

Interactions

drug adverse effects of checkpoint inhibitor(s)

General

checkpoint inhibitor; immune checkpoint inhibitor; PD-1/PD-L1 inhibitor antineoplastic monoclonal antibody

References

  1. Wikipedia: Nivolumab http://en.wikipedia.org/wiki/Nivolumab
  2. FDA News Release. March 4, 2015. FDA expands approved use of Opdivo to treat lung cancer. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm436534.htm - Chustecka Z Nivolumab in Lung Cancer Shows 'Unprecedented' Survival. Medscape Oncology. May 29, 2015. from the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. http://www.medscape.com/viewarticle/845647?nlid=82185_2202 - American Society of Clinical Oncology (ASCO) 2015 Annual Meeting: Abstract LBA109, presented May 30, 2015; abstract 8009, presented May 31, 2015
  3. Robert C, Schachter J, Long GV et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015 Apr 19; [e-pub] PMID: 25891173 http://www.nejm.org/doi/full/10.1056/NEJMoa1503093 - Postow MA et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 2015 Apr 20 PMID: 25891304 http://www.nejm.org/doi/full/10.1056/NEJMoa1414428
  4. Brahmer J et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015 May 31 PMID: 26028407
  5. Larkin J et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015 May 31; PMID: 26027431
  6. West HJ Should Atezolizumab Be the First-Choice Immunotherapy in Second-Line Non-Small Cell Lung Cancer? Medcape Oncology. Oct 31, 2016 http://www.medscape.com/viewarticle/871119
  7. Cappelli LC et al. Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab. Ann Rheum Dis 2017 Jan; 76:43 PMID: 28000525 Free Article
  8. Davenport L Clear Benefit With Adjuvant Nivolumab in Resected Melanoma Medscape - Sep 12, 2017. http://www.medscape.com/viewarticle/885539
  9. Forde PM, Chaft JE, Smith KN et al Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018 Apr 16. [Epub ahead of print] PMID: 29658848 Free Article
  10. Pal S, Phillips JD A New Path for Nivolumab? Established as second-line treatment in NSCLC, the checkpoint inhibitor navigates new therapeutic terrain (March of the Mabs, Part 2) MedPage Today. ASCO Reading Room Aug 17, 2018
  11. Hellmann MD, Ciuleanu TE, Pluzanski A et al Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med 2018; 378:2093-2104. May 31, 2018 PMID: 29658845 Free full text https://www.nejm.org/doi/full/10.1056/NEJMoa1801946
  12. Kuznar W with expert critique by Klil-Drori AJ Neoadjuvant Nivolumab Tames Resectable Merkel Cell Carcinoma. May reduce the extent of surgery required. MedPage Today. ASCO Reading Room 11.24.2018 https://www.medpagetoday.com/reading-room/asco/skin-cancer/76465
  13. Kelly RJ, Ajani JA, Kuzdzal J et al Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med 2021; 384:1191-1203. April 1. PMID: 33789008 https://www.nejm.org/doi/full/10.1056/NEJMoa2032125
  14. Bankhead C A Win for Nivolumab as Preoperative Therapy for Lung Cancer. Pathologic CR rate 12 times higher with the addition of anti-PD-1 agent to chemo. MedPage Today April 11, 2021 https://www.medpagetoday.com/meetingcoverage/aacr/92038 - Forde PM, et al Nivolumab + platinum-doublet chemotherapy vs chemotherapy as neoadjuvant treatment for resectable (Ib-IIIa) non-small cell lung cancer in the phase III CheckMate 816 trial. American Association for Cancer Research (AACR) 2021; Abstract CT003. - Bassett M First Neoadjuvant Immunotherapy OK'd in Lung Cancer - FDA approves nivolumab plus chemotherapy in resectable, non-small cell lung cancer. MedPage Today March 7, 2022 https://www.medpagetoday.com/hematologyoncology/lungcancer/97534
  15. Mulcahy N FDA Oks Nivolumab After Surgery for Esophageal of GEJ Cancer. Practice-Changing Use of Immunotherapy Medscape - May 20, 2021. https://www.medscape.com/viewarticle/951352
  16. Bajorin DF, Witjes JA, Gschwend JE Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med 2021; 384:2102-2114. June 3 PMID: 34077643 https://www.nejm.org/doi/full/10.1056/NEJMoa2034442
  17. Bassett M PD-1 Inhibitor OK'd as Adjuvant Therapy for Bladder Cancer. Nivolumab gets FDA approval for those at high risk of recurrence after surgery. MedPage Today August 20, 2021 https://www.medpagetoday.com/hematologyoncology/othercancers/94154
  18. HIGHLIGHTS OF PRESCRIBING INFORMATION OPDIVO (nivolumab) injection, for intravenous use https://packageinserts.bms.com/pi/pi_opdivo.pdf
  19. Davenport L 'Unprecedented' Responses to Neoadjuvant Treatment in dMMR Colon Cancer. Medscape. Sept 11, 2022 https://www.medscape.com/viewarticle/980548