Impact of the treatment crossover design on comparative efficacy in EMPOWER-Lung 1 : Cemiplimab monotherapy as first-line treatment of advanced non-small cell lung cancer
Copyright © 2023 Feliciano, McLoone, Xu, Quek, Kuznik, Pouliot, Gullo, Rietschel, Guyot, Konidaris, Chan, Keeping, Wilson and Freemantle..
Objectives: In randomized-controlled crossover design trials, overall survival (OS) treatment effect estimates are often confounded by the control group benefiting from treatment received post-progression. We estimated the adjusted OS treatment effect in EMPOWER-Lung 1 (NCT03088540) by accounting for the potential impact of crossover to cemiplimab among controls and continued cemiplimab treatment post-progression.
Methods: Patients were randomly assigned 1:1 to cemiplimab 350 mg every 3 weeks (Q3W) or platinum-doublet chemotherapy. Patients with disease progression while on or after chemotherapy could receive cemiplimab 350 mg Q3W for ≤108 weeks. Those who experienced progression on cemiplimab could continue cemiplimab at 350 mg Q3W for ≤108 additional weeks with four chemotherapy cycles added. Three adjustment methods accounted for crossover and/or continued treatment: simplified two-stage correction (with or without recensoring), inverse probability of censoring weighting (IPCW), and rank-preserving structural failure time model (RPSFT; with or without recensoring).
Results: In the programmed cell death-ligand 1 ≥50% population (N=563; median 10.8-month follow-up), 38.2% (n=107/280) crossed over from chemotherapy to cemiplimab (71.3%, n=107/150, among those with confirmed progression) and 16.3% (n=46/283) received cemiplimab treatment after progression with the addition of histology-specific chemotherapy (38.7%, n=46/119, among those with confirmed progression). The unadjusted OS hazard ratio (HR) with cemiplimab versus chemotherapy was 0.566 (95% confidence interval [CI]: 0.418, 0.767). Simplified two-stage correction-the most suitable method based on published guidelines and trial characteristics-produced an OS HR of 0.490 (95% CI: 0.365, 0.654) without recensoring and 0.493 (95% CI: 0.361, 0.674) with recensoring. The IPCW and RPSFT methods produced estimates generally consistent with simplified two-stage correction.
Conclusions: After adjusting for treatment crossover and continued cemiplimab treatment after progression with the addition of histology-specific chemotherapy observed in EMPOWER-Lung 1, cemiplimab continued to demonstrate a clinically important and statistically significant OS benefit versus chemotherapy, consistent with the primary analysis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Frontiers in oncology - 12(2022) vom: 13., Seite 1081729 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Feliciano, Josephine Louella [VerfasserIn] |
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| Links: |
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| Themen: |
Cemiplimab |
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| Anmerkungen: |
Date Revised 22.04.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fonc.2022.1081729 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM355858835 |
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| 100 | 1 | |a Feliciano, Josephine Louella |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Impact of the treatment crossover design on comparative efficacy in EMPOWER-Lung 1 |b Cemiplimab monotherapy as first-line treatment of advanced non-small cell lung cancer |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Revised 22.04.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Copyright © 2023 Feliciano, McLoone, Xu, Quek, Kuznik, Pouliot, Gullo, Rietschel, Guyot, Konidaris, Chan, Keeping, Wilson and Freemantle. | ||
| 520 | |a Objectives: In randomized-controlled crossover design trials, overall survival (OS) treatment effect estimates are often confounded by the control group benefiting from treatment received post-progression. We estimated the adjusted OS treatment effect in EMPOWER-Lung 1 (NCT03088540) by accounting for the potential impact of crossover to cemiplimab among controls and continued cemiplimab treatment post-progression | ||
| 520 | |a Methods: Patients were randomly assigned 1:1 to cemiplimab 350 mg every 3 weeks (Q3W) or platinum-doublet chemotherapy. Patients with disease progression while on or after chemotherapy could receive cemiplimab 350 mg Q3W for ≤108 weeks. Those who experienced progression on cemiplimab could continue cemiplimab at 350 mg Q3W for ≤108 additional weeks with four chemotherapy cycles added. Three adjustment methods accounted for crossover and/or continued treatment: simplified two-stage correction (with or without recensoring), inverse probability of censoring weighting (IPCW), and rank-preserving structural failure time model (RPSFT; with or without recensoring) | ||
| 520 | |a Results: In the programmed cell death-ligand 1 ≥50% population (N=563; median 10.8-month follow-up), 38.2% (n=107/280) crossed over from chemotherapy to cemiplimab (71.3%, n=107/150, among those with confirmed progression) and 16.3% (n=46/283) received cemiplimab treatment after progression with the addition of histology-specific chemotherapy (38.7%, n=46/119, among those with confirmed progression). The unadjusted OS hazard ratio (HR) with cemiplimab versus chemotherapy was 0.566 (95% confidence interval [CI]: 0.418, 0.767). Simplified two-stage correction-the most suitable method based on published guidelines and trial characteristics-produced an OS HR of 0.490 (95% CI: 0.365, 0.654) without recensoring and 0.493 (95% CI: 0.361, 0.674) with recensoring. The IPCW and RPSFT methods produced estimates generally consistent with simplified two-stage correction | ||
| 520 | |a Conclusions: After adjusting for treatment crossover and continued cemiplimab treatment after progression with the addition of histology-specific chemotherapy observed in EMPOWER-Lung 1, cemiplimab continued to demonstrate a clinically important and statistically significant OS benefit versus chemotherapy, consistent with the primary analysis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a EMPOWER-lung 1 | |
| 650 | 4 | |a cemiplimab | |
| 650 | 4 | |a chemotherapy | |
| 650 | 4 | |a crossover design | |
| 650 | 4 | |a first-line treatment | |
| 650 | 4 | |a non-small cell lung cancer | |
| 700 | 1 | |a McLoone, Dylan |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Yingxin |e verfasserin |4 aut | |
| 700 | 1 | |a Quek, Ruben G W |e verfasserin |4 aut | |
| 700 | 1 | |a Kuznik, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Pouliot, Jean-Francois |e verfasserin |4 aut | |
| 700 | 1 | |a Gullo, Giuseppe |e verfasserin |4 aut | |
| 700 | 1 | |a Rietschel, Petra |e verfasserin |4 aut | |
| 700 | 1 | |a Guyot, Patricia |e verfasserin |4 aut | |
| 700 | 1 | |a Konidaris, Gerasimos |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Keith |e verfasserin |4 aut | |
| 700 | 1 | |a Keeping, Sam |e verfasserin |4 aut | |
| 700 | 1 | |a Wilson, Florence R |e verfasserin |4 aut | |
| 700 | 1 | |a Freemantle, Nick |e verfasserin |4 aut | |
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