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CC BY 4.0 · Brazilian Journal of Oncology 2021; 17: e-20210015
DOI: 10.5935/2526-8732.20210015
Review Article
Clinical Oncology

Immune and targeted therapy for cancer: time to rethink restrictions for the treatment of the elderly and frail

Terapia direcionada e imunológica para o câncer: hora de repensar as restrições para o tratamento de idosos e frágeis

Juliana Rodrigues Beal
1   Hospital Israelita Albert Einstein, Medical Oncology - São Paulo - SP - Brazil
,
Gustavo Schvartsman 
1   Hospital Israelita Albert Einstein, Medical Oncology - São Paulo - SP - Brazil
,
Rodrigo Ramella Munhoz
2   Hospital Sírio-Libanes, Medical Oncology - São Paulo - SP - Brazil
,
Theodora Karnakis
3   Universidade de São Paulo, Geriatrics - São Paulo - SP - Brazil
,
Rafael Aliosha Kaliks
1   Hospital Israelita Albert Einstein, Medical Oncology - São Paulo - SP - Brazil
› Author Affiliations Financial support: none to declare.
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ABSTRACT

Targeted and immunotherapy have revolutionized cancer treatment. They safely substitute for traditional chemotherapy in a significant and growing number of malignancies. In this article, we review the United States Food and Drug Administration (FDA) - approved targeted and immunotherapies, currently used in oncology and compare their safety and efficacy in young versus geriatric and frail sub-population. The results suggest an overall comparable, if not superior efficacy in several tumor types, with acceptable toxicities across the board compared to cytotoxic chemotherapy and a favorable analysis in the comparison to the results observed in the younger population. The very decision to place elderly patients on exclusive palliative care can no longer be supported based on age or frailty alone. The historical concept of medical oncologists leaning for palliative treatments for these patients needs to be revisited.

RESUMO

A imunoterapia direcionada revolucionou o tratamento do câncer. Eles substituem com segurança a quimioterapia tradicional em um número significativo e crescente de doenças malignas. Neste artigo, revisamos a Food and Drug Administration (FDA) - imunoterapias direcionadas aprovadas atualmente usadas em oncologia, e comparamos sua segurança e eficácia na subpopulação jovem versus geriátrica e frágil. Com resultados sugerindo uma eficácia geral comparável, se não superior, em vários tipos de tumor com toxicidades aceitáveis em toda a linha em comparação com a quimioterapia citotóxica, e uma análise favorável na comparação com os resultados observados na população mais jovem. A própria decisão de colocar pacientes idosos em cuidados paliativos exclusivos não pode mais ser sustentada apenas com base na idade ou fragilidade. O conceito histórico de médicos oncologistas que buscam tratamentos paliativos para esses pacientes precisa ser revisitado.

Keywords:

Molecular targeted therapy - Immunotherapy - Therapeutics - Frail elderly - Aged.

Descritores:

Terapia de alvo molecular - Imunoterapia - Terapêutica - Idoso frágil - Envelhecido.

CONFLICT OF INTEREST STATEMENT

The authors listed below certify that they have no involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships and affiliations) in the subject matter discussed in this manuscript.

Juliana Beal

Nothing to disclose.

Gustavo Schvartsman

Participation in speakers' bureaus: Bristol-Myers Squibb, Novartis, Merck Sharp and Dohme, Sanofi, AstraZeneca, Roche, Amgen. Consultancies: AstraZeneca, Roche, Merck Sharp and Dohme.

Rodrigo Munhoz

Honoraria: Bayer, BMS, Novartis, Merck-Serono, MSD, Roche, Sanofi. Participation in speakers' bureaus: BMS, Novartis, Merck-Serono, MSD, Roche, Sanofi. Consultancies: Bayer, Merck-Serono, Roche, Sanofi.

Theodora Karnakis Nothing to disclose.

Rafael Kaliks

Participation in speakers' bureaus: Astra Zeneca; Novartis; Pfizer; Roche. Consultancies: Astra Zeneca.




Publication History

Received: 10 March 2021

Accepted: 29 March 2021

Article published online:
18 July 2021

© 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Bibliographical Record
Juliana Rodrigues Beal, Gustavo Schvartsman, Rodrigo Ramella Munhoz, Theodora Karnakis, Rafael Aliosha Kaliks. Immune and targeted therapy for cancer: time to rethink restrictions for the treatment of the elderly and frail. Brazilian Journal of Oncology 2021; 17: e-20210015.
DOI: 10.5935/2526-8732.20210015
 

  • REFERENCES

  • White MC, Holman DM, Boehm JE, Peipins LA, Grossman M, Henley SJ.. Age and cancer risk: a potentially modifiable relationship. Am J Prev Med 2014; Mar; 46 (3 Suppl 1); S7-S15
    Search in Google Scholar
  • Wildiers H, Heeren P, Puts M, Topinkova E, Janssen-Heijnen ML, Extermann M. et al International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol 2014; Aug; 32 (24) 2595-2603
    Search in Google Scholar
  • Soto-Perez-de-Celis E, Li D, Yuan Y, Lau YM, Hurria A.. Functional versus chronological age: geriatric assessments to guide decision making in older patients with cancer. Lancet Oncol 2018; Jun; 19 (06) e305-e16
    Search in Google Scholar
  • Darvin P, Toor SM, Nair VS, Elkord E.. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med 2018; Dec; 50 (12) 1-11
    Search in Google Scholar
  • Helissey C, Vicier C, Champiat S.. The development of immunotherapy in older adults: new treatments, new toxicities?. J Geriatr Oncol 2016; Sep; 7 (05) 325-333
    Search in Google Scholar
  • Hanahan D, Weinberg RA.. Hallmarks of cancer: the next generation. Cell 2011; Mar; 144 (05) 646-674
    Search in Google Scholar
  • Elias R, Karantanos T, Sira E, Hartshorn KL.. Immunotherapy comes of age: immune aging & checkpoint inhibitors. J Geriatr Oncol 2017; May; 8 (03) 229-235
    Search in Google Scholar
  • Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY. et al Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase III trial. J Clin Oncol 2020; 38 (03) 193-202
    Search in Google Scholar
  • Ready N, Hellmann MD, Awad MM, Otterson GA, Gutierrez M, Gainor JF. et al First-Line nivolumab plus ipilimumab in advanced non-small-cell lung cancer (CheckMate 568): outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers. J Clin Oncol 2019; Apr; 37 (12) 992-1000
    Search in Google Scholar
  • Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ. et al Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non- smallcell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet 2019; 393 (10183): 1819-1830
    Search in Google Scholar
  • Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A. et al Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016; Nov; 375 (+19); 1823-1833
    Search in Google Scholar
  • Elias R, Morales J, Rehman Y, Khurshid H.. Immune checkpoint inhibitors in older adults. Curr Oncol Rep 2016; Aug; 18 (08) 47
    Search in Google Scholar
  • Nishijima TF, Muss HB, Shachar SS, Moschos SJ.. Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: a systematic review and meta- analysis. Cancer Treat Rev 2016; 45: 30-37
    Search in Google Scholar
  • Bastholt L, Schmidt H, Bjerregaard JK, Herrstedt J, Svane IM.. Age favoured overall survival in a large population-based Danish patient cohort treated with anti-PD1 immune checkpoint inhibitor for metastatic melanoma. Eur J Cancer 2019; Aug; 119: 122-131
    Search in Google Scholar
  • Barlesi F, Audigier-Valette C, Felip E, Ciuleanu T, Jao K, Rijavec E. et al OA04.02 CheckMate 817: first-line nivolumab + ipilimumab in patients with ECOG PS 2 and other special populations with advanced NSCLC. J Thorac Oncol 2019; Oct; 14 (10) S214-S5
    Search in Google Scholar
  • Middleton G, Brock K, Savage J, Mant R, Summers Y, Connibear J. et al Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial. Lancet Respir Med 2020; Sep; 8 (09) 895-904
    Search in Google Scholar
  • Balar AV, Castellano D, O'Donnell PH, Grivas P, Vuky J, Powles T. et al First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol 2017; Nov; 18 (11) 1483-1492
    Search in Google Scholar
  • Spigel DR, McCleod M, Jotte RM, Einhorn L, Horn L, Waterhouse DM. et al Safety, efficacy, and patient-reported health-related quality of life and symptom burden with nivolumab in patients with advanced non-small cell lung cancer, including patients aged 70 years or older or with poor performance status (CheckMate 153). J Thorac Oncol 2019; Sep; 14 (09) 1628-1639
    Search in Google Scholar
  • Sbrana A, Antognoli R, Pasqualetti G, Linsalata G, Okoye C, Calsolaro V. et al Effectiveness of multi-prognostic index in older patients with advanced malignancies treated with immunotherapy. J Geriatr Oncol 2020; Apr; 11 (03) 503-507
    Search in Google Scholar
  • Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC, Tervahartiala P, Tuveson D. et al Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 2001; Apr; 344 (14) 1052-1056
    Search in Google Scholar
  • Garraway LA.. Genomics-driven oncology: framework for an emerging paradigm. J Clin Oncol 2013; May; 31 (15) 1806-1814
    Search in Google Scholar
  • Zehir A, Benayed R, Shah RH, Syed A, Middha S, Kim HR. et al Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med 2017; Jun; 23 (06) 703-713
    Search in Google Scholar
  • Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD. et al Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med 2018; Feb; 378 (08) 731-739
    Search in Google Scholar
  • Suidan AM, Roisman L, Rozenblum AB, Ilbouze M, Dudnik E, Zer A. et al Lung cancer in young patients: higher rate of driver mutations and brain involvement, but better survival. J Glob Oncol 2019; May; 5: 1-8
    Search in Google Scholar
  • Cancer Genome Atlas Network. Genomic classification of cutaneous melanoma. Cell 2015; Jun; 161 (07) 1681-1696
    Search in Google Scholar
  • Hutson TE, Bukowski RM, Rini BI, Gore ME, Larkin JM, Figlin RA. et al Efficacy and safety of sunitinib in elderly patients with metastatic renal cell carcinoma. Br J Cancer 2014; Mar; 110 (05) 1125-1132
    Search in Google Scholar
  • Brunello A, Basso U, Sacco C, Sava T, Vivo R, Camerini A. et al Safety and activity of sunitinib in elderly patients (>70 years) with metastatic renal cell carcinoma: a multicenter study. Ann Oncol 2013; Feb; 24 (02) 336-342
    Search in Google Scholar
  • Eisen T, Oudard S, Szczylik C, Gravis G, Heinzer H, Middleton R. et al Sorafenib for older patients with renal cell carcinoma: subset analysis from a randomized trial. J Natl Cancer Inst 2008; Oct; 100 (20) 1454-1463
    Search in Google Scholar
  • Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE. et al Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 2011; Nov; 378 (9807) 1931-1939
    Search in Google Scholar
  • Merimsky O, Cheng CK, Au JS, Von Pawel J, Reck M.. Efficacy and safety of first-line erlotinib in elderly patients with advanced non-small cell lung cancer. Oncol Rep 2012; Aug; 28 (02) 721-727
    Search in Google Scholar
  • Wheatley-Price P, Ding K, Seymour L, Clark GM, Sheperd FA.. Erlotinib for advanced non-small-cell lung cancer in the elderly: an analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 2008; May; 26 (14) 2350-2357
    Search in Google Scholar
  • Bedas A, Peled N, Rabinovich NM, Mishaeli M, Schochat T, Zer A. et al Efficacy and safety of ALK tyrosine kinase inhibitors in elderly patients with advanced alk-positive non-small cell lung cancer: findings from the real-life cohort. Oncol Res Treat 2019; 42 (05) 275-282
    Search in Google Scholar
  • Ascierto PA, McArthur GA, Dréno B, Atkinson V, Liszkay G, Di Giacomo AM. et al Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol 2016; Sep; 17 (09) 1248-1260
    Search in Google Scholar
  • Robert C, Grob JJ, Stroyakovskiy D, Karaszewska B, Hauschild A, Levchenko E. et al Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N Engl J Med 2019; Aug; 381 (07) 626-636
    Search in Google Scholar
  • Daste A, Chakiba C, Domblides C, Gross-Goupil M, Quivy A, Ravaud A. et al Targeted therapy and elderly people: a review. Eur J Cancer 2016; Dec; 69: 199-215
    Search in Google Scholar
  • Hurria A, Dale W, Mooney M, Rowland JH, Ballman KV, Cohen HJ. et al Designing therapeutic clinical trials for older and frail adults with cancer: U13 conference recommendations. J Clin Oncol 2014; Aug; 32 (24) 2587-2594
    Search in Google Scholar
  • Lewis JH, Kilgore ML, Goldman DP, Trimble EL, Kaplan R, Montello MJ. et al Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol 2003; Apr; 21 (07) 1383-1389
    Search in Google Scholar
  • Howlader N NA, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA. Surveillance, epidemiology, and end results (SEER) Program SEER*Stat Database: Mortality - Total U.S. (1969-2016). Bethesda: National Cancer Institute (NIH);; 2019
    Search in Google Scholar
  • Wildiers H, Mauer M, Pallis A, Hurria A, Mohile SG, Luciani A. et al End points and trial design in geriatric oncology research: a joint European organisation for research and treatment of cancer-- Alliance for Clinical Trials in Oncology--International Society Of Geriatric Oncology position article. J Clin Oncol 2013; Oct; 31 (29) 3711-3718
    Search in Google Scholar
  • Soubeyran P, Bellera C, Goyard J, Heitz D, Cure H, Rousselot H. et al Screening for vulnerability in older cancer patients: the ONCODAGE prospective multicenter cohort study. PLoS One 2014; Dec; 9 (12) e115060
    Search in Google Scholar
  • Owusu C, Koroukian SM, Schluchter M, Bakaki P, Berger NA.. Screening older cancer patients for a comprehensive geriatric assessment: a comparison of three instruments. J Geriatr Oncol 2011; Apr; 2 (02) 121-129
    Search in Google Scholar
  • Luo J, Rizvi H, Egger JV, Preeshagul IR, Wolchok JD, Hellman MD.. Impact of PD-1 blockade on severity of COVID19 in patients with lung cancers. Cancer Discovery 2020; May; 12; Epub ahead of print.
    Search in Google Scholar