nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.02.2020 | Original Article – Clinical Oncology

Efficacy and safety of first-line pembrolizumab monotherapy in elderly patients (aged ≥ 75 years) with non-small cell lung cancer

verfasst von: Hisao Imai, Satoshi Wasamoto, Ou Yamaguchi, Kensuke Suzuki, Tomohide Sugiyama, Junji Uchino, Hiroyuki Minemura, Takashi Osaki, Hisashi Ishii, Yukihiro Umeda, Keita Mori, Mie Kotake, Hiroshi Kagamu, Nobutoshi Morozumi, Hirokazu Taniguchi, Takashi Kasai, Koichi Minato, Kyoichi Kaira

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2020

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Pembrolizumab is an effective front-line treatment for advanced non-small cell lung cancer (NSCLC) in patients expressing high levels of programmed death-ligand 1 (PD-L1). However, it is unclear whether first-line pembrolizumab has similar efficacy among elderly (aged ≥ 75 years) and younger patients. This study aimed to investigate the safety and efficacy of front-line pembrolizumab monotherapy in older adults with NSCLC expressing high PD-L1.

Methods

A total of 128 patients with advanced NSCLC expressing high PD-L1, including 47 older adults, received first-line pembrolizumab monotherapy at ten institutions in Japan, between February 2017 and February 2018. Data related to patient characteristics, efficacy of pembrolizumab therapy, and the type and severity of adverse events were recorded.

Results

Overall, 47 patients [40 men and 7 women; median age 79 (range 75–88) years] were included in our analysis. In patients who received first-line pembrolizumab monotherapy, overall response, disease control rates, median progression-free survival (PFS), and median overall survival (OS) were 53.1%, 74.4%, 7.0 months, and not reached, respectively. Common adverse events included anorexia, fatigue, skin rash, and hypothyroidism. Two treatment-related deaths were noted, due to pneumonitis and infection. First-line pembrolizumab monotherapy was associated with improved PFS in patients with non-progressive disease (PD). In patients with non-PD and good performance status (PS), pembrolizumab monotherapy improved OS.

Conclusions

Elderly patients with NSCLC expressing high PD-L1 tolerated front-line pembrolizumab monotherapy well. Their survival outcomes were equivalent to those of younger patients. In patients with non-PD, first-line pembrolizumab monotherapy may improve PFS; in conjunction with good PS, it additionally improves OS.

Alguilar EJ et al (2018) MA04. 05 outcomes in NSCLC patients treated with first-line pembrolizumab and a PD-L1 TPS of 50-74% vs 75-100% or 50-89% vs 90-100%. J Thorac Oncol 13:S367–S368CrossRef

Alkharabsheh O, Kannarkatt P, Kannarkatt J, Karapetyan L, Laird-Fick HS, Al-Janadi A (2018) An overview of the toxicities of checkpoint inhibitors in older patients with cancer. J Geriatr Oncol 9:451–458. https://doi.org/10.1016/j.jgo.2018.02.002 CrossRefPubMed

Champiat S et al (2016) Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann Oncol 27:559–574. https://doi.org/10.1093/annonc/mdv623 CrossRefPubMed

Daste A et al (2017) Immune checkpoint inhibitors and elderly people: a review. Eur J Cancer 82:155–166. https://doi.org/10.1016/j.ejca.2017.05.044 CrossRefPubMed

Davidoff AJ, Tang M, Seal B, Edelman MJ (2010) Chemotherapy and survival benefit in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol 28:2191–2197. https://doi.org/10.1200/jco.2009.25.4052 CrossRefPubMed

Dudnik E et al (2018) Effectiveness and safety of nivolumab in advanced non-small cell lung cancer: the real-life data. Lung Cancer 126:217–223. https://doi.org/10.1016/j.lungcan.2017.11.015 CrossRefPubMed

Eisenhauer EA et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247. https://doi.org/10.1016/j.ejca.2008.10.026 CrossRefPubMed

Ferlay J et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386. https://doi.org/10.1002/ijc.29210 CrossRefPubMed

Fujimoto D et al (2018) Efficacy and safety of nivolumab in previously treated patients with non-small cell lung cancer: a multicenter retrospective cohort study. Lung Cancer 119:14–20. https://doi.org/10.1016/j.lungcan.2018.02.017 CrossRefPubMed

Gandhi L et al (2018) Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 378:2078–2092. https://doi.org/10.1056/nejmoa1801005 CrossRefPubMed

Garon EB et al (2015) Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372:2018–2028. https://doi.org/10.1056/nejmoa1501824 CrossRefPubMed

Gridelli C et al (2003) Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst 95:362–372CrossRefPubMed

Haratani K et al (2018) Association of immune-related adverse events with nivolumab efficacy in non-small-cell lung cancer. JAMA Oncol 4:374–378. https://doi.org/10.1001/jamaoncol.2017.2925 CrossRefPubMed

Hellmann MD et al (2018) Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med 378:2093–2104. https://doi.org/10.1056/nejmoa1801946 CrossRefPubMedPubMedCentral

Herbst RS et al (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387:1540–1550. https://doi.org/10.1016/s0140-6736(15)01281-7 CrossRefPubMed

Kudoh S et al (2006) Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). J Clin Oncol 24:3657–3663. https://doi.org/10.1200/jco.2006.06.1044 CrossRefPubMed

Miller KD et al (2016) Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin 66:271–289. https://doi.org/10.3322/caac.21349 CrossRefPubMed

Nosaki K et al (2019) Safety and efficacy of pembrolizumab monotherapy in elderly patients with PD-L1-positive advanced non-small-cell lung cancer: pooled analysis from the KEYNOTE-010, KEYNOTE-024, and KEYNOTE-042 studies. Lung Cancer 135:188–195. https://doi.org/10.1016/j.lungcan.2019.07.004 CrossRefPubMed

Okamoto I et al (2019) Randomized phase III study comparing carboplatin plus pemetrexed followed by pemetrexed versus docetaxel in elderly patients with advanced non-squamous non-small-cell lung cancer (JCOG1210/WJOG7813L). J Clin Oncol 37 (suppl; abstr 9031)

Owonikoko TK, Ragin CC, Belani CP, Oton AB, Gooding WE, Taioli E, Ramalingam SS (2007) Lung cancer in elderly patients: an analysis of the surveillance, epidemiology, and end results database. J Clin Oncol 25:5570–5577. https://doi.org/10.1200/jco.2007.12.5435 CrossRefPubMed

Pang HH et al (2016) Enrollment trends and disparity among patients with lung cancer in National Clinical Trials, 1990 to 2012. J Clin Oncol 34:3992–3999. https://doi.org/10.1200/jco.2016.67.7088 CrossRefPubMedPubMedCentral

Poropatich K, Fontanarosa J, Samant S, Sosman JA, Zhang B (2017) Cancer immunotherapies: are they as effective in the elderly? Drugs Aging 34:567–581. https://doi.org/10.1007/s40266-017-0479-1 CrossRefPubMed

Reck M et al (2016) Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 375:1823–1833. https://doi.org/10.1056/nejmoa1606774 CrossRefPubMed

Rizvi NA et al (2015) 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 16:257–265. https://doi.org/10.1016/s1470-2045(15)70054-9 CrossRefPubMedPubMedCentral

Roach C et al (2016) Development of a companion diagnostic PD-L1 immunohistochemistry assay for pembrolizumab therapy in non-small-cell lung cancer. Appl Immunohistochem Mol Morphol 24:392–397. https://doi.org/10.1097/pai.0000000000000408 CrossRefPubMedPubMedCentral

Sacher AG, Le LW, Leighl NB, Coate LE (2013) Elderly patients with advanced NSCLC in phase III clinical trials: are the elderly excluded from practice-changing trials in advanced NSCLC? J Thorac Oncol 8:366–368. https://doi.org/10.1097/jto.0b013e31827e2145 CrossRefPubMed

Singh S, Loke YK (2012) Drug safety assessment in clinical trials: methodological challenges and opportunities. Trials 13:138. https://doi.org/10.1186/1745-6215-13-138 CrossRefPubMedPubMedCentral

Socinski MA et al (2018) Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med 378:2288–2301. https://doi.org/10.1056/nejmoa1716948 CrossRefPubMed

Solana R, Tarazona R, Gayoso I, Lesur O, Dupuis G, Fulop T (2012) Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans. Semin Immunol 24:331–341. https://doi.org/10.1016/j.smim.2012.04.008 CrossRefPubMed

Tomihara K, Curiel TJ, Zhang B (2013) Optimization of immunotherapy in elderly cancer patients. Crit Rev Oncog 18:573–583CrossRefPubMedPubMedCentral

Townsley CA, Selby R, Siu LL (2005) Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials. J Clin Oncol 23:3112–3124. https://doi.org/10.1200/jco.2005.00.141 CrossRefPubMed

Townsley CA, Chan KK, Pond GR, Marquez C, Siu LL, Straus SE (2006) Understanding the attitudes of the elderly towards enrolment into cancer clinical trials. BMC Cancer 6:34. https://doi.org/10.1186/1471-2407-6-34 CrossRefPubMedPubMedCentral

Titel: Efficacy and safety of first-line pembrolizumab monotherapy in elderly patients (aged ≥ 75 years) with non-small cell lung cancer
verfasst von: Hisao Imai
Satoshi Wasamoto
Ou Yamaguchi
Kensuke Suzuki
Tomohide Sugiyama
Junji Uchino
Hiroyuki Minemura
Takashi Osaki
Hisashi Ishii
Yukihiro Umeda
Keita Mori
Mie Kotake
Hiroshi Kagamu
Nobutoshi Morozumi
Hirokazu Taniguchi
Takashi Kasai
Koichi Minato
Kyoichi Kaira
Publikationsdatum: 01.02.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2020
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-03072-1

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Efficacy and safety of first-line pembrolizumab monotherapy in elderly patients (aged ≥ 75 years) with non-small cell lung cancer