Efficacy of PD-(L)1 blockade monotherapy compared to PD-(L)1 blockade plus chemotherapy in first-line PD-L1-positive advanced lung adenocarcinomas: A cohort study
ABSTRACT Background Single-agent PD-(L)1 blockade (IO) alone or in combination with chemotherapy (Chemotherapy-IO) are approved first-line therapies in patients with advanced lung adenocarcinomas (LUADs) with PD-L1 expression ≥1%. These regimens have not been compared prospectively. The primary objective was to compare first-line efficacies of single-agent IO to Chemotherapy-IO in patients with advanced LUADs. Secondary objectives were to explore if clinical, pathologic, and genomic features were associated with differential response to Chemotherapy-IO vs IO.Methods This was a multicenter retrospective cohort study. Inclusion criteria were patients with advanced LUADs with tumor PD-L1 ≥1% treated with first-line Chemotherapy-IO or IO. To compare the first-line efficacies of single-agent IO to Chemotherapy-IO, we conducted inverse probability weighted (IPW) Cox proportional hazards models using estimated propensity scores.Results The cohort analyzed included 874 patients. Relative to IO, Chemotherapy-IO was associated with improved ORR (44% vs 35%, p=0.005) and PFS in patients with tumor PD-L1≥1% (HR 0.75, 95% CI 0.0.61-0.92, p=0.005) or PD-L1≥50% (ORR 55% vs38%, p<0.001; PFS HR 0.74 95%CI 0.56-0.97, p=0.032). Using propensity-adjusted analyses, only never smokers in the PD-L1 ≥50% subgroup derived a differential survival benefit from Chemotherapy-IO vs IO (p=0.03). Among patients with very high tumor PD-L1 expression (≥90%) there were no differences in outcome between treatment groups. No genomic factors conferred differential survival benefit to Chemotherapy-IO vs IO.Conclusions While the addition of chemotherapy to PD-(L)1 blockade increases the probability of initial response, never-smokers with tumor PD-L1 ≥50% comprise the only population identified that derived an apparent survival benefit with treatment intensification..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 23. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Elkrief, Arielle [VerfasserIn] |
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| doi: |
10.1101/2022.12.05.22283131 |
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| PPN (Katalog-ID): |
XBI038084155 |
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| 245 | 1 | 0 | |a Efficacy of PD-(L)1 blockade monotherapy compared to PD-(L)1 blockade plus chemotherapy in first-line PD-L1-positive advanced lung adenocarcinomas: A cohort study |
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| 520 | |a ABSTRACT Background Single-agent PD-(L)1 blockade (IO) alone or in combination with chemotherapy (Chemotherapy-IO) are approved first-line therapies in patients with advanced lung adenocarcinomas (LUADs) with PD-L1 expression ≥1%. These regimens have not been compared prospectively. The primary objective was to compare first-line efficacies of single-agent IO to Chemotherapy-IO in patients with advanced LUADs. Secondary objectives were to explore if clinical, pathologic, and genomic features were associated with differential response to Chemotherapy-IO vs IO.Methods This was a multicenter retrospective cohort study. Inclusion criteria were patients with advanced LUADs with tumor PD-L1 ≥1% treated with first-line Chemotherapy-IO or IO. To compare the first-line efficacies of single-agent IO to Chemotherapy-IO, we conducted inverse probability weighted (IPW) Cox proportional hazards models using estimated propensity scores.Results The cohort analyzed included 874 patients. Relative to IO, Chemotherapy-IO was associated with improved ORR (44% vs 35%, p=0.005) and PFS in patients with tumor PD-L1≥1% (HR 0.75, 95% CI 0.0.61-0.92, p=0.005) or PD-L1≥50% (ORR 55% vs38%, p<0.001; PFS HR 0.74 95%CI 0.56-0.97, p=0.032). Using propensity-adjusted analyses, only never smokers in the PD-L1 ≥50% subgroup derived a differential survival benefit from Chemotherapy-IO vs IO (p=0.03). Among patients with very high tumor PD-L1 expression (≥90%) there were no differences in outcome between treatment groups. No genomic factors conferred differential survival benefit to Chemotherapy-IO vs IO.Conclusions While the addition of chemotherapy to PD-(L)1 blockade increases the probability of initial response, never-smokers with tumor PD-L1 ≥50% comprise the only population identified that derived an apparent survival benefit with treatment intensification. | ||
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| 700 | 1 | |a Preeshagul, Isabel R. |e verfasserin |4 aut | |
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