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Treatment-Free Survival After Nivolumab vs Pembrolizumab vs Nivolumab-Ipilimumab for Advanced Melanoma

IMPORTANCE: Treatment-free survival (TFS) represents an alternative time-to-event end point, accurately characterizing time spent free of systemic therapy, providing a more patient-centric view of immune checkpoint inhibitor (ICI) therapy regimens. There remains a lack of studies evaluating TFS outc...

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Autores principales: Gupta, Mehul, Stukalin, Igor, Meyers, Daniel, Goutam, Sid, Heng, Daniel Y. C., Cheng, Tina, Monzon, Jose, Navani, Vishal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10290253/
https://www.ncbi.nlm.nih.gov/pubmed/37351883
http://dx.doi.org/10.1001/jamanetworkopen.2023.19607
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author Gupta, Mehul
Stukalin, Igor
Meyers, Daniel
Goutam, Sid
Heng, Daniel Y. C.
Cheng, Tina
Monzon, Jose
Navani, Vishal
author_facet Gupta, Mehul
Stukalin, Igor
Meyers, Daniel
Goutam, Sid
Heng, Daniel Y. C.
Cheng, Tina
Monzon, Jose
Navani, Vishal
author_sort Gupta, Mehul
collection PubMed
description IMPORTANCE: Treatment-free survival (TFS) represents an alternative time-to-event end point, accurately characterizing time spent free of systemic therapy, providing a more patient-centric view of immune checkpoint inhibitor (ICI) therapy regimens. There remains a lack of studies evaluating TFS outcomes among patients with advanced melanoma who are receiving immunotherapy, especially outside of the clinical trial setting. OBJECTIVE: To evaluate TFS outcomes for patients with advanced melanoma receiving first-line ICI therapy outside of a clinical trial setting. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study of patients with advanced melanoma receiving first-line ICI therapy between August 1, 2013, and May 31, 2020, was conducted in Alberta, Canada. Data analysis was performed in August 2022. EXPOSURES: Patients received standard-of-care, first-line ICI therapy treatment regimens including single-agent nivolumab, single-agent pembrolizumab, or ipilimumab-nivolumab. MAIN OUTCOMES AND MEASURES: Treatment-free survival was defined as the difference in the 36-month restricted mean survival time between 2 conventional survival end points: (1) time from treatment initiation to ICI cessation, death, or censoring at last follow-up and (2) time from treatment initiation to subsequent systemic anticancer therapy, death, or censoring at last follow-up. RESULTS: A total of 316 patients with advanced melanoma receiving first-line nivolumab (n = 51; median age, 66 years [IQR, 56-78 years]; 31 men [60.8%]), pembrolizumab (n = 158; median age, 69 years [IQR, 60-78 years]; 112 men [70.9%]), or combination nivolumab-ipilimumab (n = 107; median age, 53 years [IQR, 42-60 years]; 72 men [67.3%]) were included. Treatment groups were similar with regard to sex, primary tumor location, and presence of metastasis, although patients receiving combination nivolumab-ipilimumab had a lower Eastern Cooperative Oncology Group status, were younger, and were more likely to be BRAF V600E positive than those receiving anti–programmed cell death protein 1 (anti–PD-1) monotherapy. The restricted mean TFS was longer for nivolumab-ipilimumab (12.4 months [95% CI, 8.8-16.0 months]) compared with nivolumab (8.9 months [95% CI, 4.4-13.5 months]) and pembrolizumab (11.1 months [95% CI, 8.5-13.8 months]). During the 36-month follow-up interval, patients treated with nivolumab-ipilimumab spent 34.4% of their time (12.4 of 36 months) not receiving systemic anticancer treatments compared with 30.8% (11.1 of 36 months) and 24.7% (8.9 of 36 months) of the time for the pembrolizumab and nivolumab treatment groups, respectively. CONCLUSIONS AND RELEVANCE: This cohort study of patients with advanced melanoma receiving first-line ICI therapy suggests that TFS represents a patient-centric, informative end point. Patients treated with combination nivolumab-ipilimumab spent more time alive and free from systemic anticancer therapy than those treated with anti–PD-1 monotherapy alone.
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spelling pubmed-102902532023-06-25 Treatment-Free Survival After Nivolumab vs Pembrolizumab vs Nivolumab-Ipilimumab for Advanced Melanoma Gupta, Mehul Stukalin, Igor Meyers, Daniel Goutam, Sid Heng, Daniel Y. C. Cheng, Tina Monzon, Jose Navani, Vishal JAMA Netw Open Original Investigation IMPORTANCE: Treatment-free survival (TFS) represents an alternative time-to-event end point, accurately characterizing time spent free of systemic therapy, providing a more patient-centric view of immune checkpoint inhibitor (ICI) therapy regimens. There remains a lack of studies evaluating TFS outcomes among patients with advanced melanoma who are receiving immunotherapy, especially outside of the clinical trial setting. OBJECTIVE: To evaluate TFS outcomes for patients with advanced melanoma receiving first-line ICI therapy outside of a clinical trial setting. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study of patients with advanced melanoma receiving first-line ICI therapy between August 1, 2013, and May 31, 2020, was conducted in Alberta, Canada. Data analysis was performed in August 2022. EXPOSURES: Patients received standard-of-care, first-line ICI therapy treatment regimens including single-agent nivolumab, single-agent pembrolizumab, or ipilimumab-nivolumab. MAIN OUTCOMES AND MEASURES: Treatment-free survival was defined as the difference in the 36-month restricted mean survival time between 2 conventional survival end points: (1) time from treatment initiation to ICI cessation, death, or censoring at last follow-up and (2) time from treatment initiation to subsequent systemic anticancer therapy, death, or censoring at last follow-up. RESULTS: A total of 316 patients with advanced melanoma receiving first-line nivolumab (n = 51; median age, 66 years [IQR, 56-78 years]; 31 men [60.8%]), pembrolizumab (n = 158; median age, 69 years [IQR, 60-78 years]; 112 men [70.9%]), or combination nivolumab-ipilimumab (n = 107; median age, 53 years [IQR, 42-60 years]; 72 men [67.3%]) were included. Treatment groups were similar with regard to sex, primary tumor location, and presence of metastasis, although patients receiving combination nivolumab-ipilimumab had a lower Eastern Cooperative Oncology Group status, were younger, and were more likely to be BRAF V600E positive than those receiving anti–programmed cell death protein 1 (anti–PD-1) monotherapy. The restricted mean TFS was longer for nivolumab-ipilimumab (12.4 months [95% CI, 8.8-16.0 months]) compared with nivolumab (8.9 months [95% CI, 4.4-13.5 months]) and pembrolizumab (11.1 months [95% CI, 8.5-13.8 months]). During the 36-month follow-up interval, patients treated with nivolumab-ipilimumab spent 34.4% of their time (12.4 of 36 months) not receiving systemic anticancer treatments compared with 30.8% (11.1 of 36 months) and 24.7% (8.9 of 36 months) of the time for the pembrolizumab and nivolumab treatment groups, respectively. CONCLUSIONS AND RELEVANCE: This cohort study of patients with advanced melanoma receiving first-line ICI therapy suggests that TFS represents a patient-centric, informative end point. Patients treated with combination nivolumab-ipilimumab spent more time alive and free from systemic anticancer therapy than those treated with anti–PD-1 monotherapy alone. American Medical Association 2023-06-23 /pmc/articles/PMC10290253/ /pubmed/37351883 http://dx.doi.org/10.1001/jamanetworkopen.2023.19607 Text en Copyright 2023 Gupta M et al. JAMA Network Open. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Gupta, Mehul
Stukalin, Igor
Meyers, Daniel
Goutam, Sid
Heng, Daniel Y. C.
Cheng, Tina
Monzon, Jose
Navani, Vishal
Treatment-Free Survival After Nivolumab vs Pembrolizumab vs Nivolumab-Ipilimumab for Advanced Melanoma
title Treatment-Free Survival After Nivolumab vs Pembrolizumab vs Nivolumab-Ipilimumab for Advanced Melanoma
title_full Treatment-Free Survival After Nivolumab vs Pembrolizumab vs Nivolumab-Ipilimumab for Advanced Melanoma
title_fullStr Treatment-Free Survival After Nivolumab vs Pembrolizumab vs Nivolumab-Ipilimumab for Advanced Melanoma
title_full_unstemmed Treatment-Free Survival After Nivolumab vs Pembrolizumab vs Nivolumab-Ipilimumab for Advanced Melanoma
title_short Treatment-Free Survival After Nivolumab vs Pembrolizumab vs Nivolumab-Ipilimumab for Advanced Melanoma
title_sort treatment-free survival after nivolumab vs pembrolizumab vs nivolumab-ipilimumab for advanced melanoma
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10290253/
https://www.ncbi.nlm.nih.gov/pubmed/37351883
http://dx.doi.org/10.1001/jamanetworkopen.2023.19607
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