Immunotherapy in Elderly Patients Affected by Non-Small Cell Lung Cancer: A Narrative Review
Abstract
:1. Introduction
2. Definition of Older Patient
3. Immunosenescence
4. PD-1/PD-L1 Axis Inhibition in the Second-Line Setting
5. PD-1/PD-L1 Axis Inhibition in the First-Line Setting
6. First-Line ICIs-Chemotherapy Combinations
7. First-Line ICI-ICI Combinations
8. Observational and Real-World Setting Studies in Advanced Stage Disease
9. Locally Advanced Disease
10. Perioperative Immunotherapy
11. Case Reports
12. Discussion
13. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study [Ref] | Drug | Setting | Population | Age (Years) | Patients n. | OS HR (95% CI) |
---|---|---|---|---|---|---|
CM 017 [34] | Nivolumab vs. Docetaxel | 2L | NSCLC squamous, PD-L1 any | <65 | 152 | 0.52 (0.35–0.75) |
≥65–75 | 91 | 0.56 (0.34–0.91) | ||||
≥75 | 29 | 1.85 (0.76–4.51) | ||||
CM 057 [35] | Nivolumab vs. Docetaxel | 2L–3L | NSCLC nonsquamous PD-L1 any | <65 | 333 | 0.81 (0.62–1.04) |
≥65–75 | 200 | 0.63 (0.45–0.89) | ||||
≥75 | 43 | 0.90 (0.43–1.87) | ||||
Pooled CM 017—CM 057 [36] | Nivolumab vs. Docetaxel | 2L | NSCLC, PD-L1 any | <65 | 491 | 0.66 |
≥65–75 | 363 | 0.71 | ||||
≥75 | 72 | 1.19 | ||||
KN-010 [37] | Pembrolizumab vs. Docetaxel | ≥2L | NSCLC, PD-L1 ≥ 1% | <65 | 604 | 0.62 (0.52–0.65) |
≥65 | 429 | 0.80 (0.64–1.01) | ||||
OAK [38] | Atezolizumab vs. Docetaxel | 2L–3L | NSCLC, PD-L1 any | <65 | 453 | 0.80 (0.64–1.00) |
≥65 yr | 397 | 0.66 (0.52–0.83) | ||||
KN-024 [39] | Pembrolizumab vs. standard platinum doublet chemotherapy | 1L | NSCLC, PD-L1 ≥ 50% | <65 | 141 | 0.60 (0.38–0.96) |
≥65 | 164 | 0.64 (0.42–0.98) | ||||
KN-042 [40] | Pembrolizumab vs. standard platinum doublet chemotherapy | 1L | NSCLC, PD-L1 ≥ 1% | <65 | 707 | 0.81 (0.60–1.08) |
≥65 | 567 | 0.82 (0.66–1.01) | ||||
Pooled KN-010—KN-024—KN-042 [41] | Pembrolizumab vs. standard chemotherapy | ≥1L | NSCLC, PD-L1 ≥ 1% | <75 | 2348 | 0.76 (0.69–0.84) |
≥75 | 264 | 0.76 (0.56–1.02) | ||||
Pooled KN-010—KN-024—KN-042 [41] | Pembrolizumab vs. standard chemotherapy | ≥1L | NSCLC, PD-L1 ≥ 50% | <75 | 1214 | 0.67 (0.57–0.78) |
≥75 | 132 | 0.40 (0.25–0.64) | ||||
Pooled KN-010—KN-024—KN-042 [41] | Pembrolizumab vs. standard chemotherapy | 1L | NSCLC, PD-L1 ≥ 50% | <75 | 811 | 0.71 (0.59–0.87) |
≥75 | 93 | 0.41 (0.23–0.73) | ||||
IMpower110 [42] | Atezolizumab vs. standard platinum doublet chemotherapy | 1L | NSCLC, PD-L1 TPS ≥ 50%/TC ≥ 10 | <65 | 102 | 0.72 (0.44–1.19) |
65–74 | 80 | 0.78 (0.45–1.36) | ||||
>74 | 23 | 1.03 (0.31–3.48) | ||||
EMPOWER-Lung 1 [43] | Cemiplimab vs. standard platinum doublet chemotherapy | 1L | NSCLC, PD-L1 ≥ 50% | <65 | 157 | 0.66 (0.44–1.0) |
≥65 | 126 | 0.48 (0.30–0.66) | ||||
IPSOS [44] | Atezolizumab vs. single agent Gemcitabine or Vinorelbine | 1L | NSCLC, PD-L1 any | <70 | 123 | 0.75 (0.49–1.14) |
70–79 | 190 | 0.68 (0.49–0.94) | ||||
≥80 | 140 | 0.97 (0.66–1.44) | ||||
KN-189 [45] | Pembrolizumab + Platinum-Pemetrexed vs. Platinum-Pemetrexed | 1L | NSCLC, PD-L1 any | <65 | 312 | 0.49 (0.37–0.65) |
≥65 | 304 | 0.72 (0.54–0.97) | ||||
KN-407 [46] | Pembrolizumab + Carboplatin-(Nab)Paclitaxel vs. Carboplatin-(Nab)Paclitaxel | 1L | NSCLC, PD-L1 any | <65 | 254 | 0.52 (0.34–0.80 |
≥65 | 305 | 0.74 (0.51–1.07) | ||||
EMPOWER-Lung 3 [47] | Cemiplimab + Platinum doublet chemotherapy vs. Platinum doublet chemotherapy | 1L | NSCLC, PD-L1 any | <65 | 278 | 0.57 (0.40–0.81) |
≥65 | 188 | 0.88 (0.56–1.37) | ||||
IMpower131 [48] | Atezolizumab + Carboplatin-(Nab)Paclitaxel vs. Carboplatin-(Nab)Paclitaxel | 1L | NSCLC squamous, PD-L1 any | <65 | 326 | 0.89 (0.68–1.15) |
65–74 | 279 | 0.84 (0.63–1.13) | ||||
75–84 | 77 | 0.74 (0.45–1.23) | ||||
IMpower150 [49] | Atezolizumab + Carboplatin-Paclitaxel + Bevacizumab vs. Carboplatin-Paclitaxel + Bevacizumab | 1L | NSCLC nonsquamous, PD-L1 any | <65 | 441 | 0.83 (0.65–1.04) |
65–74 | 281 | 0.72 (CI, 0.54–0.97) | ||||
75–84 | 72 | 0.97 (0.58–1.62) | ||||
CM 227 [50] | Nivolumab + Ipilimumab vs. standard platinum doublet chemotherapy | 1L | NSCLC, PD-L1 ≥ 1% | <65 | 406 | 0.72 (0.55–0.93) |
65–74 | 306 | 0.85 (0.64–1.13) | ||||
≥75 | 81 | 0.95 (0.56–1.62) | ||||
CM 227 [50] | Nivolumab + Ipilimumab vs. standard platinum doublet chemotherapy | 1L | NSCLC, PD-L1 < 1% | <65 | 205 | 0.70 (0.50–0.97) |
65–74 | 136 | 0.61 (0.40–0.63) | ||||
≥75 | 32 | 0.65 (0.25–1.68) | ||||
CM 9LA [51] | Nivolumab + Ipilimumab + 2 courses chemotherapy vs. standard platinum doublet chemotherapy | 1L | NSCLC, PD-L1 any | <65 | 354 | 0.64 (0.5–0.82) |
65–74 | 295 | 0.78 (0.59–1.02) | ||||
≥75 | 70 | 1.04 (0.63–1.72) |
Ref | Drug | Setting | Age | Histology | PD-L1 TPS (%) | Best Response | irAEs | irAE Outcome | irAE Treatment | ICIs therapy |
---|---|---|---|---|---|---|---|---|---|---|
Nakako S, 2022 [144] | Pembrolizumab + Chemotherapy | NR | 72 | NSCLC | NR | NR | Delayed G4 neutropenia at 92 and 118 days after pembrolizumab discontinuation | Resolved | SC | Discontinued |
Dhenin A, 2019 [153] | Pembrolizumab | 1L | 79 | ADC | 100 | CR | Rash, pericarditis, colitis and myasthenia gravis | Resolved | SC | Resumed |
Cham J, 2021 [154] | Durvalumab | Post-CRT | 72 | ADC | 80 | NE | Myocarditis, myasthenia gravis, and myositis | Death | SC | Discontinued |
Strickley JD, 2019 [135] | Nivolumab | 2L | 87 | NSCLC | NR | SD | Lichen Planus Pemphigoides | Resolved | SC | Discontinued |
Gracia-Cazaña T [136] | Nivolumab | NR | 78 | SCC | NR | PD | Stevens-Johnson syndrome | Resolved | SC | Discontinued |
Kim YE, 2019 [137] | Nivolumab | NR | 74 | NSCLC | NR | NR | Psoriasiform dermatitis | Resolved | Etanercept + Methotrexate | Discontinued |
Lopez AT, 2018 [138] | Nivolumab | 1L | 72 | SCC | 0 | NR | Bollous pemphigoid | Resolved | SC | Discontinued |
Cosimati A, 2020 [139] | Pembrolizumab | 1L | 77 | ADC | 55 | SD | Bollous pemphigoid | Resolved | SC + doxycycline, nicotinamide, and clobetasol propionate | Discontinued |
Muto Y, 2020 [140] | Pembrolizumab | NR | 84 | NSCLC | ≥50% | CR | Bollous pemphigoid | Resolved | SC | Discontinued |
Yoshikawa Y, 2021 [141] | Nivolumab | 1L | 75 | NSCLC | NR | NR | Secondary sclerosing cholangitis | Death | SC + mycophenolate mofetil | Discontinued |
Hamoir C, 2018 [142] | Nivolumab | 2L | 71 | NSCLC | NR | PD | Intrahepatic cholangitis | Resolved | SC + Ursodeoxycholic acid | Discontinued |
Gelsomino F, 2017 [143] | Nivolumab | NR | 79 | NSCLC | NR | PD | Cholangitis | Resolved | SC + Ursodeoxycholic acid | Discontinued |
Nakamura M, 2020 [145] | Durvalumab | Post-CRT | 79 | ADC | NR | NR | Immune-related hepatitis | Resolved | SC | Discontinued |
Miyauchi M, 2020 [146] | Nivolumab | NR | 79 | NSCLC | NR | NR | Type 1 diabetes mellitus | Ongoing | Insulin | Discontinued |
Seo JH, 2022 [147] | Nivolumab | 2L | 74 | ADC | 40 | SD | Type 1 diabetes mellitus | Ongoing | Insulin | Discontinued |
Matsuura N, 2018 [148] | Nivolumab | 2L | 78 | NSCLC | NR | NR | Type 1 diabetes mellitus | Ongoing | Insulin | Resumed |
Kajal S, 2021 [149] | Nivolumab | 3L | 84 | ADC | NR | NR | Hypophysitis | Improved | SC | Resumed |
Galliazzo S, 2022 [150] | Nivolumab | NR | 74 | SCC | NR | NR | Primary adrenal insufficiency | Improved | Glucocorticoid + mineralocorticoid | NR |
Kim J, 2019 [151] | Nivolumab | 2L | 76 | NSCLC | 75 | PR | Myasthenia Gravis and Myopathy | Improved | SC + ivIg | Discontinued |
Hasegawa Y, 2017 [152] | Nivolumab | 3L | 76 | ADC | NR | PD | Myasthenia gravis | Improved | SC + ivIg | Discontinued |
Tan JL, 2019 [155] | Nivolumab | 2L | 74 | ADC | NR | NR | Myocarditis and complete atrioventricular block | Improved | SC | Discontinued |
Semper H, 2016 [156] | Nivolumab | 2L | 75 | ADC | 0 | PR | Myocarditis | Improved | SC | Discontinued |
Katsume Y, 2018 [157] | Pembrolizumab | 2L | 73 | NSCLC | NR | NR | Myocarditis and complete atrioventricular block | Improved | SC | Discontinued |
Samejima Y, 2020 [158] | Nivolumab | 2L | 79 | SCC | NR | PR | Severe Heart Failure | Improved | Diuretics, | Discontinued |
Berry EC, 2022 [159] | Atezolizumab | 2L | 83 | ADC | NR | NR | Arteritic Anterior Ischemic Optic Neuropathy | NE | SC + Methotrexate | Discontinued |
Gupta S, 2020 [160] | Durvalumab | Post-CRT | 80 | NSCLC | NR | NR | Vasculitis (blue toe syndrome) | Improved | SC | Discontinued |
Suwa S, 2022 [161] | Atezolizumab | 2L | 76 | NSCLC | NR | NR | Vogt–Koyanagi–Harada Disease-like Uveitis | Improved | SC | Discontinued |
Shiral AC, 2016 [162] | Nivolumab | 4L | 73 | SCC | NR | NR | Acute Interstitial Nephritis | Improved | SC | Resumed |
Nivolumab | 4L | 78 | ADC | NR | NR | Acute Interstitial Nephritis | Resolved | SC | Discontinued | |
Taki T, 2020 [134] | Pembrolizumab | 2L | 75 | ADC | 25–49 | PR | Tubulointerstitial Nephritis | Improved | SC | Discontinued |
Takahashi N, 2018 [163] | Nivolumab | 2L | 74 | ADC | NR | PR | Goodpasture’s disease | Death | SC + plasma exchange | Discontinued |
Narumi Y, 2018 [164] | Nivolumab | 2L | 75 | SCC | NR | PD | Neuromyelitis optica spectrum disorder | Improved | SC + plasma exchange | Discontinued |
Makri OE, 2022 [165] | Pembrolizumab | 2L | 76 | NSCLC | NR | NR | Optic Neuritis | Improved | SC | Discontinued |
Richard K, 2017 [166] | Nivolumab | 2L | 74 | NSCLC | NR | NR | Encephalitis | Improved | SC | Discontinued |
Lou Y, 2019 [167] | Nivolumab | 2L | 73 | ADC | NR | PR | Recurrent Hypereosinophilia | Improved | NR | Discontinued |
Turgeman I, 2017 [168] | Nivolumab | 3L | 74 | ADC | NR | PR | Severe Neutropenia | Improved | SC | Discontinued |
Tabchi S, 2016 [169] | Nivolumab | 2L | 74 | ADC | NR | NR | Severe agranulocytosis | NR | SC + ivIg | Discontinued |
Naqash AR, 2019 [170] | Pembrolizumab | 2L | 74 | ADC | 50 | PR | Recurrent febrile neutropenia | Death | SC | Discontinued |
Karakas Y, 2017 [171] | Nivolumab | 2L | 78 | NSCLC | NR | PD | Immune Thrombocytopenia | Improved | SC | Discontinued |
Okawa S, 2019 [172] | Pembrolizumab | 1L | 78 | SCC | >50 | PR | Autoimmune hemolytic anemia and hemophagocytic lymphohistiocytosis | Improved | SC | Discontinued |
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Montrone, M.; Rosati, G.; Longo, V.; Catino, A.; Massafra, R.; Nardone, A.; Pesola, F.; Montagna, E.S.; Marech, I.; Pizzutilo, P.; et al. Immunotherapy in Elderly Patients Affected by Non-Small Cell Lung Cancer: A Narrative Review. J. Clin. Med. 2023, 12, 1833. https://doi.org/10.3390/jcm12051833
Montrone M, Rosati G, Longo V, Catino A, Massafra R, Nardone A, Pesola F, Montagna ES, Marech I, Pizzutilo P, et al. Immunotherapy in Elderly Patients Affected by Non-Small Cell Lung Cancer: A Narrative Review. Journal of Clinical Medicine. 2023; 12(5):1833. https://doi.org/10.3390/jcm12051833
Chicago/Turabian StyleMontrone, Michele, Gerardo Rosati, Vito Longo, Annamaria Catino, Raffaella Massafra, Annalisa Nardone, Francesco Pesola, Elisabetta Sara Montagna, Ilaria Marech, Pamela Pizzutilo, and et al. 2023. "Immunotherapy in Elderly Patients Affected by Non-Small Cell Lung Cancer: A Narrative Review" Journal of Clinical Medicine 12, no. 5: 1833. https://doi.org/10.3390/jcm12051833