Refining patient selection for next-generation immunotherapeutic early-phase clinical trials with a novel and externally validated prognostic nomogram
Copyright © 2024 Losurdo, Dipasquale, Giordano, Persico, Lorenzi, Di Muzio, Barigazzi, Korolewicz, Mehan, Mohammed, Scheiner, Pinato, Santoro and Simonelli..
Introduction: Identifying which patient may benefit from immunotherapeutic early-phase clinical trials is an unmet need in drug development. Among several proposed prognostic scores, none has been validated in patients receiving immunomodulating agents (IMAs)-based combinations.
Patients and methods: We retrospectively collected data of 208 patients enrolled in early-phase clinical trials investigating IMAs at our Institution, correlating clinical and blood-based variables with overall survival (OS). A retrospective cohort of 50 patients treated with IMAs at Imperial College (Hammersmith Hospital, London, UK) was used for validation.
Results: A total of 173 subjects were selected for analyses. Most frequent cancers included non-small cell lung cancer (26%), hepatocellular carcinoma (21.5%) and glioblastoma (13%). Multivariate analysis (MVA) revealed 3 factors to be independently associated with OS: line of treatment (second and third vs subsequent, HR 0.61, 95% CI 0.40-0.93, p 0.02), serum albumin as continuous variable (HR 0.57, 95% CI 0.36-0.91, p 0.02) and number of metastatic sites (<3 vs ≥3, HR 0.68, 95% CI 0.48-0.98, p 0.04). After splitting albumin value at the median (3.84 g/dL), a score system was capable of stratifying patients in 3 groups with significantly different OS (p<0.0001). Relationship with OS reproduced in the external cohort (p=0.008). Then, from these factors we built a nomogram.
Conclusions: Prior treatment, serum albumin and number of metastatic sites are readily available prognostic traits in patients with advanced malignancies participating into immunotherapy early-phase trials. Combination of these factors can optimize patient selection at study enrollment, maximizing therapeutic intent.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Frontiers in immunology - 15(2024) vom: 01., Seite 1323151 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Losurdo, Agnese [VerfasserIn] |
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| Links: |
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| Themen: |
Early-phases clinical trials |
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| Anmerkungen: |
Date Completed 02.02.2024 Date Revised 04.04.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2024.1323151 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM367874962 |
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| 245 | 1 | 0 | |a Refining patient selection for next-generation immunotherapeutic early-phase clinical trials with a novel and externally validated prognostic nomogram |
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| 520 | |a Copyright © 2024 Losurdo, Dipasquale, Giordano, Persico, Lorenzi, Di Muzio, Barigazzi, Korolewicz, Mehan, Mohammed, Scheiner, Pinato, Santoro and Simonelli. | ||
| 520 | |a Introduction: Identifying which patient may benefit from immunotherapeutic early-phase clinical trials is an unmet need in drug development. Among several proposed prognostic scores, none has been validated in patients receiving immunomodulating agents (IMAs)-based combinations | ||
| 520 | |a Patients and methods: We retrospectively collected data of 208 patients enrolled in early-phase clinical trials investigating IMAs at our Institution, correlating clinical and blood-based variables with overall survival (OS). A retrospective cohort of 50 patients treated with IMAs at Imperial College (Hammersmith Hospital, London, UK) was used for validation | ||
| 520 | |a Results: A total of 173 subjects were selected for analyses. Most frequent cancers included non-small cell lung cancer (26%), hepatocellular carcinoma (21.5%) and glioblastoma (13%). Multivariate analysis (MVA) revealed 3 factors to be independently associated with OS: line of treatment (second and third vs subsequent, HR 0.61, 95% CI 0.40-0.93, p 0.02), serum albumin as continuous variable (HR 0.57, 95% CI 0.36-0.91, p 0.02) and number of metastatic sites (<3 vs ≥3, HR 0.68, 95% CI 0.48-0.98, p 0.04). After splitting albumin value at the median (3.84 g/dL), a score system was capable of stratifying patients in 3 groups with significantly different OS (p<0.0001). Relationship with OS reproduced in the external cohort (p=0.008). Then, from these factors we built a nomogram | ||
| 520 | |a Conclusions: Prior treatment, serum albumin and number of metastatic sites are readily available prognostic traits in patients with advanced malignancies participating into immunotherapy early-phase trials. Combination of these factors can optimize patient selection at study enrollment, maximizing therapeutic intent | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a early-phases clinical trials | |
| 650 | 4 | |a immune-related adverse events | |
| 650 | 4 | |a immunotherapy | |
| 650 | 4 | |a next-generations immunotherapies | |
| 650 | 4 | |a prognostic scores | |
| 650 | 7 | |a Serum Albumin |2 NLM | |
| 700 | 1 | |a Dipasquale, Angelo |e verfasserin |4 aut | |
| 700 | 1 | |a Giordano, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Persico, Pasquale |e verfasserin |4 aut | |
| 700 | 1 | |a Lorenzi, Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Di Muzio, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Barigazzi, Chiara |e verfasserin |4 aut | |
| 700 | 1 | |a Korolewicz, James |e verfasserin |4 aut | |
| 700 | 1 | |a Mehan, Aman |e verfasserin |4 aut | |
| 700 | 1 | |a Mohammed, Oreoluwa |e verfasserin |4 aut | |
| 700 | 1 | |a Scheiner, Benhard |e verfasserin |4 aut | |
| 700 | 1 | |a Pinato, David J |e verfasserin |4 aut | |
| 700 | 1 | |a Santoro, Armando |e verfasserin |4 aut | |
| 700 | 1 | |a Simonelli, Matteo |e verfasserin |4 aut | |
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