4CPS-175 Effectiveness of immunotherapy as a function of age: meta-analysis of the approved combinations in first-line metastatic non-small-cell lung cancer in patients without mutations Article Swipe

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A Aguado Paredes , Emilio Jesús Alegre Del Rey ·

YOU? · · 2024 · Open Access · · DOI: https://doi.org/10.1136/ejhpharm-2024-eahp.279

Background and Importance It could be hypothesised that patients older than 65 years old may experience decreased immune function due to the natural aging process, which could lead to a more limited response to immunotherapy compared to those younger than 65 years old. The forest-plot analysis for age-dependent overall survival from the clinical trial of cemiplimab in combination with chemotherapy in locally advanced or metastatic non-small-cell lung cancer (NSCLC), EMPOWER-Lung 3, showed a borderline interaction between the subgroups younger and older than 65 years old, with a p-interaction=0.0895 (own calculation) and HR 0.53 (0.39–0.72), HR 0.81 (0.55–1.18), respectively. Aim and Objectives To verify the consistency of the hypothesis of an age-related effectiveness by a meta-analysis considering all approved immunotherapy combinations in first-line NSCLC. Material and Methods A MEDLINE-PubMed literature search was conducted for phase III randomised clinical trials (RCTs) with similar population and duration of pembrolizumab, atezolizumab ± bevacizumab, nivolumab + ipilimumab, durvalumab + tremelimumab and cemiplimab, in combination with chemotherapy and nivolumab + ipilimumab. A meta-analysis was performed with the MetaSurv calculator. The primary endpoint was overall survival (OS) in patients younger and older than, or equal to, 65 years of age. Age-dependent OS data for immunotherapy combinations versus a common comparator, platinum-based chemotherapy, were compared. Interaction was considered significative if p<0.05 and doubtful if 0.05≤p<0.1. Results A pooled HR of 0.67 (95% CI 0.58–0.76), p<0.000001 was obtained in patients younger than 65 years of age. Heterogeneity among trials estimate values were as follows: Q 14.84, p=0.03812. I2 53% (CI 95% 0–79%). In those older than 65 years old, the combined HR obtained was 0.77 (95% CI 0.70–0.84), p<0.000001. Heterogeneity estimate values were as follows: Q for heterogeneity 0.81 p=0.99733. I2 0% (CI 95% 0–0%). The calculated p-interaction between the combined HRs of the under-65 and over-65 groups was 0.0551, which is considered a doubtful interaction in a subgroup analysis. Conclusion and Relevance A significant benefit for immunotherapy-chemotherapy over chemotherapy alone was shown in both age groups. There is some consistency regarding a greater effectiveness of immunotherapy in patients under 65 years of age, but more data would be needed to confirm this possible difference. References and/or Acknowledgements Conflict of Interest No conflict of interest.

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Ipilimumab Medicine Nivolumab Atezolizumab Internal medicine Oncology Durvalumab Pembrolizumab Lung cancer Bevacizumab Meta-analysis Population Immunotherapy Chemotherapy Cancer Environmental health

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Type: article
Language: en
Landing Page: https://doi.org/10.1136/ejhpharm-2024-eahp.279
PDF: https://ejhp.bmj.com/content/ejhpharm/31/Suppl_1/A135.2.full.pdf
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Title: 4CPS-175 Effectiveness of immunotherapy as a function of age: meta-analysis of the approved combinations in first-line metastatic non-small-cell lung cancer in patients without mutations

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Publication year: 2024

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Authors: A Aguado Paredes, Emilio Jesús Alegre Del Rey

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Concepts: Ipilimumab, Medicine, Nivolumab, Atezolizumab, Internal medicine, Oncology, Durvalumab, Pembrolizumab, Lung cancer, Bevacizumab, Meta-analysis, Population, Immunotherapy, Chemotherapy, Cancer, Environmental health

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abstract_inverted_index.younger	38, 78, 182, 231
abstract_inverted_index.(NSCLC),	68
abstract_inverted_index.0–0%).	285
abstract_inverted_index.MetaSurv	171
abstract_inverted_index.advanced	62
abstract_inverted_index.analysis	45
abstract_inverted_index.approved	117
abstract_inverted_index.clinical	52, 136
abstract_inverted_index.combined	261, 291
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abstract_inverted_index.conflict	363
abstract_inverted_index.doubtful	214, 305
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abstract_inverted_index.endpoint	175
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abstract_inverted_index.obtained	228, 263
abstract_inverted_index.patients	8, 181, 230, 339
abstract_inverted_index.possible	354
abstract_inverted_index.process,	24
abstract_inverted_index.response	32
abstract_inverted_index.subgroup	309
abstract_inverted_index.survival	49, 178
abstract_inverted_index.under-65	295
abstract_inverted_index.0–79%).	252
abstract_inverted_index.analysis.	310
abstract_inverted_index.compared.	206
abstract_inverted_index.conducted	131
abstract_inverted_index.decreased	16
abstract_inverted_index.interest.	365
abstract_inverted_index.nivolumab	149, 162
abstract_inverted_index.p<0.05	212
abstract_inverted_index.performed	168
abstract_inverted_index.regarding	332
abstract_inverted_index.subgroups	77
abstract_inverted_index.borderline	73
abstract_inverted_index.calculated	287
abstract_inverted_index.cemiplimab	55
abstract_inverted_index.considered	209, 303
abstract_inverted_index.durvalumab	152
abstract_inverted_index.experience	15
abstract_inverted_index.first-line	121
abstract_inverted_index.hypothesis	107
abstract_inverted_index.literature	128
abstract_inverted_index.metastatic	64
abstract_inverted_index.p=0.03812.	247
abstract_inverted_index.p=0.99733.	280
abstract_inverted_index.population	141
abstract_inverted_index.randomised	135
abstract_inverted_index.Interaction	207
abstract_inverted_index.age-related	110
abstract_inverted_index.calculator.	172
abstract_inverted_index.cemiplimab,	156
abstract_inverted_index.combination	57, 158
abstract_inverted_index.comparator,	202
abstract_inverted_index.considering	115
abstract_inverted_index.consistency	104, 331
abstract_inverted_index.difference.	355
abstract_inverted_index.forest-plot	44
abstract_inverted_index.interaction	74, 306
abstract_inverted_index.ipilimumab,	151
abstract_inverted_index.ipilimumab.	164
abstract_inverted_index.significant	315
abstract_inverted_index.<h3>Conflict	359
abstract_inverted_index.<h3>Material	123
abstract_inverted_index.EMPOWER-Lung	69
abstract_inverted_index.Methods</h3>	125
abstract_inverted_index.atezolizumab	146
abstract_inverted_index.bevacizumab,	148
abstract_inverted_index.calculation)	89
abstract_inverted_index.chemotherapy	59, 160, 320
abstract_inverted_index.combinations	119, 198
abstract_inverted_index.hypothesised	6
abstract_inverted_index.tremelimumab	154
abstract_inverted_index.0.58–0.76),	225
abstract_inverted_index.0.70–0.84),	268
abstract_inverted_index.Age-dependent	193
abstract_inverted_index.Heterogeneity	237, 270
abstract_inverted_index.Interest</h3>	361
abstract_inverted_index.age-dependent	47
abstract_inverted_index.chemotherapy,	204
abstract_inverted_index.effectiveness	111, 335
abstract_inverted_index.heterogeneity	278
abstract_inverted_index.immunotherapy	34, 118, 197, 337
abstract_inverted_index.meta-analysis	114, 166
abstract_inverted_index.p<0.000001	226
abstract_inverted_index.p-interaction	288
abstract_inverted_index.respectively.	97
abstract_inverted_index.significative	210
abstract_inverted_index.(0.39–0.72),	93
abstract_inverted_index.(0.55–1.18),	96
abstract_inverted_index.<h3>Background	0
abstract_inverted_index.<h3>Conclusion	311
abstract_inverted_index.<h3>References	356
abstract_inverted_index.MEDLINE-PubMed	127
abstract_inverted_index.Relevance</h3>	313
abstract_inverted_index.non-small-cell	65
abstract_inverted_index.p<0.000001.	269
abstract_inverted_index.pembrolizumab,	145
abstract_inverted_index.platinum-based	203
abstract_inverted_index.Importance</h3>	2
abstract_inverted_index.Objectives</h3>	100
abstract_inverted_index.0.05≤p<0.1.	216
abstract_inverted_index.<h3>Results</h3>	217
abstract_inverted_index.p-interaction=0.0895	87
abstract_inverted_index.Acknowledgements</h3>	358
abstract_inverted_index.immunotherapy-chemotherapy	318
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