Skip to main content

Advertisement

SpringerLink
Log in

Immune Checkpoint Inhibitors in Older Adults

  • Geriatric Oncology (AR MacKenzie, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Cancer is primarily a disease of older adults. The treatment of advanced stage tumors usually involves the use of systemic agents that may be associated with significant risk of toxicity, especially in older patients. Immune checkpoint inhibitors are newcomers to the oncology world with improved efficacy and better safety profiles when compared to traditional cytotoxic drugs. This makes them an attractive treatment option. While there are no elderly specific trials, this review attempts to look at the current available data from a geriatric oncology perspective. We reviewed data from phase III studies that led to newly approved indications of checkpoint inhibitors in non-small cell lung cancer, melanoma, and renal cell cancer. Data were reviewed with respect to response, survival, and toxicity according to three groups: <65 years, 65–75 years, and >75 years. Current literature does not allow one to draw definitive conclusions regarding the role of immune checkpoint inhibitors in older adults. However, they may offer a potentially less toxic but equally efficacious treatment option for the senior adult oncology patient.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Cancer of all sites - SEER Stat Fact Sheets. 2016.

  2. Walker LS, Sansom DM. The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat Rev Immunol. 2011;11:852–63.

    Article  CAS  PubMed  Google Scholar 

  3. Francisco LM, Salinas VH, Brown KE, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206:3015–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Browse the SEER Cancer Statistics Review 1975–2012. 2016.

  5. Shepherd FA, Dancey J, Ramlau R, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000;18:2095–103.

    CAS  PubMed  Google Scholar 

  6. Shepherd FA, Fossella FV, Lynch T, et al. Docetaxel (Taxotere) shows survival and quality-of-life benefits in the second-line treatment of non-small cell lung cancer: a review of two phase III trials. Semin Oncol. 2001;28:4–9.

    Article  CAS  PubMed  Google Scholar 

  7. Fossella FV, DeVore R, Kerr RN, et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol. 2000;18:2354–62.

    CAS  PubMed  Google Scholar 

  8. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123–35. Patients with advanced progressive squamous-cell NSCLC have significant improvement in their overall survival, response rate, and progression-free survival with nivolumab compared to docetaxel.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627–39. Patients with advanced progressive nonsquamous NSCLC have significant improvement in their overall survival, response rate, and progression-free survival with nivolumab compared to docetaxel.

    Article  CAS  PubMed  Google Scholar 

  10. Horn L, Brahmer J, Reck M, et al. Phase 3, randomized trial (CheckMate 057) of nivolumab vs docetaxel in advanced non-squamous (non-SQ) non-small cell lung cancer (NSCLC): subgroup analyses and patient reported outcomes (PROs). Ann Oncol. 2015;26, ix125.

    Article  Google Scholar 

  11. Rizvi NA, Mazieres J, Planchard D, et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015;16:257–65.

    Article  CAS  PubMed  Google Scholar 

  12. Gettinger SN, Horn L, Ramalingam SS, et al. Nivolumab (NIVO) safety profile: summary of findings from trials in patients (pts) with advanced squamous (SQ) non-small cell lung cancer (NSCLC). Eur J Cancer. 2015;51:S631.

    Article  Google Scholar 

  13. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372:2018–28.

    Article  PubMed  Google Scholar 

  14. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet, 2015. In patients with advanced previously treated PD-L1 positive NSCLC pemrbolizumab is associated with improved OS and favorable risk-benefit ratio compared to docetaxel.

  15. Lewis JH, Kilgore ML, Goldman DP, et al. Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol. 2003;21:1383–9.

    Article  PubMed  Google Scholar 

  16. Pawelec G, Derhovanessian E, Larbi A. Immunosenescence and cancer. Crit Rev Oncol Hematol. 2010;75:165–72.

    Article  PubMed  Google Scholar 

  17. Tsaknaridis L, Spencer L, Culbertson N, et al. Functional assay for human CD4+CD25+ Treg cells reveals an age-dependent loss of suppressive activity. J Neurosci Res. 2003;74:296–308.

    Article  CAS  PubMed  Google Scholar 

  18. Melanoma of the skin—SEER Stat Fact Sheets. 2016.

  19. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23. Patients with previously treated metastatic melanoma have better survival with ipilimumab compared to gp100 peptide vaccine.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Squibb B-M. Highlights of prescribing information: Yervoy.

  21. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364:2517–26. Combination of ipilimumab and dacarbazine is superior to dacarbazine monotherapy in patients with previously untreated metastatic melanoma.

    Article  CAS  PubMed  Google Scholar 

  22. Weber JS, D’Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;16:375–84. Nivolumab is associated with improved response rates and fewer toxic effects compared to chemotherapy in patients with advanced melanoma that has progressed after ipilimumab or ipilimumab and a BRAF inhibitor.

    Article  CAS  PubMed  Google Scholar 

  23. Squibb B-M. Highlights of prescribing information: Opdivo.

  24. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–30. Untreated patients with BRAF wild-type metastatic melanoma have significant improvement in their overall survival and progressions-free survival with nivolumab compared to dacarbazine.

    Article  CAS  PubMed  Google Scholar 

  25. Postow MA, Chesney J, Pavlick AC, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372:2006–17.

    Article  PubMed  Google Scholar 

  26. Hodi FS, Postow MA, Chesney JA, et al. Clinical response, progression-free survival (PFS), and safety in patients (pts) with advanced melanoma (MEL) receiving nivolumab (NIVO) combined with ipilimumab (IPI) vs IPI monotherapy in CheckMate 069 study. J Clin Oncol. 2015;33:1.

    Article  Google Scholar 

  27. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23–34. In patients with previously untreated metastatic melanoma nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone.

    Article  PubMed  Google Scholar 

  28. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–32. Compared to ipilimumab, pembrolizumab prolongs progression-free survival and overall survival with less high-grade toxicity in patients with advanced melanoma.

    Article  CAS  PubMed  Google Scholar 

  29. Merck. Highlights of prescribing information: Keytruda

  30. Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med. 2005;353:2477–90.

    Article  CAS  PubMed  Google Scholar 

  31. Cancer of the kidney and renal pelvis—SEER Stat Fact Sheets. 2016

  32. Fyfe G, Fisher RI, Rosenberg SA, et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995;13:688–96.

    CAS  PubMed  Google Scholar 

  33. Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803–13. Patients with previously treated advanced renal-cell carcinoma have an improved overall survival and fewer grade 3 or 4 adverse events with nivolumab compared to everolimus.

    Article  CAS  PubMed  Google Scholar 

  34. Nivolumab combined with ipilimumab versus sunitinib in previously untreated advanced or metastatic renal cell carcinoma (CheckMate 214) - Full text view - ClinicalTrials.gov. 2016.

  35. Disis JSW, James CY, Michael BA, et al. Toxicities of immunotherapy for the practitioner. 2015.

  36. Nagele EP, Han M, Acharya NK, et al. Natural IgG autoantibodies are abundant and ubiquitous in human sera, and their number is influenced by age, gender, and disease. PLoS One. 2013;8, e60726.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology-Oncology and Department of Geriatrics, Boston University Medical Center, 820 Harrison Ave, Boston, MA, 02118, USA

    Rawad Elias & Yasser Rehman

  2. Division of Hematology-Oncology, Virginia Commonwealth University, 1200 East Broad Street, Richmond, VA, 23298, USA

    Joshua Morales

  3. Division of Hematology-Oncology, Rhode Island Hospital, 593 Eddy St, Providence, RI, 02903, USA

    Humera Khurshid

Authors
  1. Rawad Elias
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joshua Morales
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yasser Rehman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Humera Khurshid
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rawad Elias.

Ethics declarations

Conflict of Interest

Rawad Elias, Joshua Morales, Yasser Rehman, and Humera Khurshid declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Geriatric Oncology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Elias, R., Morales, J., Rehman, Y. et al. Immune Checkpoint Inhibitors in Older Adults. Curr Oncol Rep 18, 47 (2016). https://doi.org/10.1007/s11912-016-0534-9

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11912-016-0534-9

Keywords

Search

Navigation