LAG3-PD1 or CTLA4-PD1 Inhibition in Advanced Melanoma: Indirect Cross Comparisons of the CheckMate-067 and RELATIVITY-047 Trials
<b>Objective:</b> To compare the inhibition of LAG3-PD1 versus the inhibition of CTLA-4-PD1 in patients with previously untreated advanced melanoma. <b>Methods:</b> The individual participant data (IPD) were extracted from the KM plots using a graphical reconstructive algorit...
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MDPI AG
2022-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/20/4975 |
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| author | Bai-Wei Zhao Fei-Yang Zhang Yun Wang Guo-Ming Chen Man Nie Zhou-Kai Zhao Xiao-Jiang Chen Kai-Ming Jiang Run-Cong Nie Ying-Bo Chen |
| author_facet | Bai-Wei Zhao Fei-Yang Zhang Yun Wang Guo-Ming Chen Man Nie Zhou-Kai Zhao Xiao-Jiang Chen Kai-Ming Jiang Run-Cong Nie Ying-Bo Chen |
| author_sort | Bai-Wei Zhao |
| collection | DOAJ |
| description | <b>Objective:</b> To compare the inhibition of LAG3-PD1 versus the inhibition of CTLA-4-PD1 in patients with previously untreated advanced melanoma. <b>Methods:</b> The individual participant data (IPD) were extracted from the KM plots using a graphical reconstructive algorithm. Log-rank, Cox proportional hazard model, Bayesian hierarchical model with time-varying hazard ratio (HR) effect, and restricted mean survival time (RMST) were performed to estimate survival benefits. <b>Results:</b> The CheckMate-067 (<i>n</i> = 630) and RELATIVITY-047 (<i>n</i> = 714) trials were included for analysis. The graphical reconstructive algorithm showed that IPD had similar HRs and log-rank values as the original plots. The HR of nivolumab plus relatlimab (LAG3 inhibitor) versus nivolumab plus ipilimumab (CTLA4 inhibitor) was 1.19 (95% confidence interval [CI] 0.96 to1.48). The 24-months RMST of nivolumab plus relatlimab versus nivolumab was 2.35 (95% CI 0.77–3.94) months, compared with 1.87 (95% CI, 0.25–3.49) months for nivolumab plus ipilimumab versus nivolumab. The Bayesian hierarchical model showed that patients treated with nivolumab plus relatlimab had earlier PFS benefits than those with nivolumab plus ipilimumab. Grade 3 or 4 treatment-related adverse events occurred in 18.9% of patients using nivolumab plus relatlimab and 55.0% of patients using nivolumab plus ipilimumab. <b>Conclusions:</b> These findings suggest that the PFS of LAG3-PD1 and CTLA4-PD1 inhibition were similar and LAG3-PD1 inhibition exhibited earlier survival benefit and lesser TRAEs. |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T20:32:18Z |
| publishDate | 2022-10-01 |
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| series | Cancers |
| spelling | doaj.art-a1dda287990f4f73934573e6df2b41e12023-11-23T23:19:56ZengMDPI AGCancers2072-66942022-10-011420497510.3390/cancers14204975LAG3-PD1 or CTLA4-PD1 Inhibition in Advanced Melanoma: Indirect Cross Comparisons of the CheckMate-067 and RELATIVITY-047 TrialsBai-Wei Zhao0Fei-Yang Zhang1Yun Wang2Guo-Ming Chen3Man Nie4Zhou-Kai Zhao5Xiao-Jiang Chen6Kai-Ming Jiang7Run-Cong Nie8Ying-Bo Chen9Department of Gastric Surgery & Melanoma Surgical Section, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaDepartment of Gastric Surgery & Melanoma Surgical Section, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaDepartment of Hematologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaDepartment of Gastric Surgery & Melanoma Surgical Section, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaDepartment of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaDepartment of Gastric Surgery & Melanoma Surgical Section, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaDepartment of Gastric Surgery & Melanoma Surgical Section, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaDepartment of Gastric Surgery & Melanoma Surgical Section, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaDepartment of Gastric Surgery & Melanoma Surgical Section, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaDepartment of Gastric Surgery & Melanoma Surgical Section, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China<b>Objective:</b> To compare the inhibition of LAG3-PD1 versus the inhibition of CTLA-4-PD1 in patients with previously untreated advanced melanoma. <b>Methods:</b> The individual participant data (IPD) were extracted from the KM plots using a graphical reconstructive algorithm. Log-rank, Cox proportional hazard model, Bayesian hierarchical model with time-varying hazard ratio (HR) effect, and restricted mean survival time (RMST) were performed to estimate survival benefits. <b>Results:</b> The CheckMate-067 (<i>n</i> = 630) and RELATIVITY-047 (<i>n</i> = 714) trials were included for analysis. The graphical reconstructive algorithm showed that IPD had similar HRs and log-rank values as the original plots. The HR of nivolumab plus relatlimab (LAG3 inhibitor) versus nivolumab plus ipilimumab (CTLA4 inhibitor) was 1.19 (95% confidence interval [CI] 0.96 to1.48). The 24-months RMST of nivolumab plus relatlimab versus nivolumab was 2.35 (95% CI 0.77–3.94) months, compared with 1.87 (95% CI, 0.25–3.49) months for nivolumab plus ipilimumab versus nivolumab. The Bayesian hierarchical model showed that patients treated with nivolumab plus relatlimab had earlier PFS benefits than those with nivolumab plus ipilimumab. Grade 3 or 4 treatment-related adverse events occurred in 18.9% of patients using nivolumab plus relatlimab and 55.0% of patients using nivolumab plus ipilimumab. <b>Conclusions:</b> These findings suggest that the PFS of LAG3-PD1 and CTLA4-PD1 inhibition were similar and LAG3-PD1 inhibition exhibited earlier survival benefit and lesser TRAEs.https://www.mdpi.com/2072-6694/14/20/4975PD-1CTLA4LAG3melanomaimmunotherapy |
| spellingShingle | Bai-Wei Zhao Fei-Yang Zhang Yun Wang Guo-Ming Chen Man Nie Zhou-Kai Zhao Xiao-Jiang Chen Kai-Ming Jiang Run-Cong Nie Ying-Bo Chen LAG3-PD1 or CTLA4-PD1 Inhibition in Advanced Melanoma: Indirect Cross Comparisons of the CheckMate-067 and RELATIVITY-047 Trials Cancers PD-1 CTLA4 LAG3 melanoma immunotherapy |
| title | LAG3-PD1 or CTLA4-PD1 Inhibition in Advanced Melanoma: Indirect Cross Comparisons of the CheckMate-067 and RELATIVITY-047 Trials |
| title_full | LAG3-PD1 or CTLA4-PD1 Inhibition in Advanced Melanoma: Indirect Cross Comparisons of the CheckMate-067 and RELATIVITY-047 Trials |
| title_fullStr | LAG3-PD1 or CTLA4-PD1 Inhibition in Advanced Melanoma: Indirect Cross Comparisons of the CheckMate-067 and RELATIVITY-047 Trials |
| title_full_unstemmed | LAG3-PD1 or CTLA4-PD1 Inhibition in Advanced Melanoma: Indirect Cross Comparisons of the CheckMate-067 and RELATIVITY-047 Trials |
| title_short | LAG3-PD1 or CTLA4-PD1 Inhibition in Advanced Melanoma: Indirect Cross Comparisons of the CheckMate-067 and RELATIVITY-047 Trials |
| title_sort | lag3 pd1 or ctla4 pd1 inhibition in advanced melanoma indirect cross comparisons of the checkmate 067 and relativity 047 trials |
| topic | PD-1 CTLA4 LAG3 melanoma immunotherapy |
| url | https://www.mdpi.com/2072-6694/14/20/4975 |
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