Programmed Death-1 or Programmed Death Ligand-1 Blockade in Patients with Platinum-resistant Metastatic Urothelial Cancer: A Systematic Review and Meta-analysis

Niglio, Scot A.; Jia, Rachel; Ji, Jiayi; Ruder, Samuel; Patel, Vaibhav; Martini, Alberto; Sfakianos, John P.; Marqueen, Kathryn E.; Waingankar, Nikhil; Mehrazin, Reza; Wiklund, Peter; Oh, William; Mazumdar, Madhu; Ferket, Bart S.; Galsky, Matthew D.

doi:10.1016/j.eururo.2019.05.037

Cited by 43 publications

(35 citation statements)

References 30 publications

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“…Most responders (16/22) had achieved partial response at the first efficacy assessment (six weeks after the first dose). The PFS of 6.9 months observed in our study is numerically longer than the PFS results obtained from second-line ICI treatments (2.1 to 4.0 months) (18). focused on mUC patients with HER2 overexpression.…”

Section: Discussioncontrasting

confidence: 66%

Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody–Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma

Sheng

Yan

Wang

et al. 2021

Clinical Cancer Research

184

129

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Platinum-containing chemotherapy is the standard first-line treatment in metastatic urothelial carcinoma (mUC). After the disease progression on standard first-line chemotherapy, anti-PD-1/PD-L1 therapies have emerged as a second-line option but have yielded low response rates in unselected population. Following breast and gastric cancer, UC is the third most prevalent cancer with HER2 overexpression, indicating a potential utility for HER2-targeting therapy in mUC. However, antibodies and tyrosine kinase inhibitors targeting HER2, have failed to show clinical benefits in metastatic UC. This phase 2 clinical trial assessed RC48-ADC, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E (MMAE), in 43 patients with HER2-positive (IHC 3+ and 2+) locally advanced or metastatic UC who progressed on systemic chemotherapy. We observed an objective response rate of 51.2% and progression-free survival of 6.9 months, showing a higher response rate than historic response rates of currently available immunotherapies in the second-line setting. The efficacy observed in this trial is promising for patients with HER2-positive metastatic UC, which remained an unmet clinical need. Research.

show abstract

Section: Discussioncontrasting

confidence: 66%

Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody–Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma

Sheng

Yan

Wang

et al. 2021

Clinical Cancer Research

184

129

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“…A prospective cohort study exploring the relationship between midlife cardiorespiratory fitness and chronic obstructive pulmonary disease performed both Cox models and RMST analysis, estimated HR and changes in RMST of incidence of COPD and presented death simultaneously, which increased the reliability and understandability of the conclusion [14]. In addition to original studies, RMST and difference in RMST have been considered as effect measures in meta-analysis [15,16]. RMST was regarded as an obligatory end point, while HR and difference in RMST as complementary methods to summarize treatment effect in oncological trials [17].…”

Section: Resultsmentioning

confidence: 99%

A univariable and multivariable analysis of time-to-event data based on restricted mean survival time: A combination with traditional survival methods.

Huang¹,

Lyv²,

Ma³

et al. 2019

Preprint

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Background Hazard ratio is considered as an appropriate effect measure of time-to-event data. However, hazard ratio is only valid when proportional hazards (PH) assumption is met. The use of the restricted mean survival time (RMST) is proposed and recommended without limitation of PH assumption. Method 4405 osteosarcomas were captured from Surveillance, Epidemiology and End Results Program Database. Traditional survival analyses and RMST-based analyses were integrated into a flowchart and applied for univariable and multivariable analyses, using hazard ratio (HR) and difference in RMST (survival time lost or gain, STL or STG) as effect measures. The relationship between difference in RMST and HR were explored when PH assumption was and was not met, respectively. Results In univariable analyses, using difference in RMST calculated by Kaplan-Meier methods as reference, pseudo-value regressions (R2=0.99) and inverse probability of censoring probability (IPCW) regressions with group-specific weights (R2=1.00) provided more consistent estimation on difference in RMST than IPCW with individual weights (R2=0.09). In multivariable analysis, age (HR:1.03, STL: 3.86 months), diagnosis in 1970~1980s (HR:1.39 STL:27.49 months), metastasis (HR:4.47, STL: 202 months), surgery (HR:0.58, SLG:35.55 months) and radiation (HR:1.46, SLT:44.65 months), met PH assumption and were main independent factors for overall survival. In both univariable and multivariable variables, a robust negative logarithmic linear relationship between HRs estimated by Cox regression and differences in RMST by pseudo-value regressions was only observed when PH assumption was hold (Difference in RMST = -109.3✕ln (HR) - 0.83, R² = 0.97, and Difference = -127.7✕ln (HR) – 9.49, R² = 0.93, respectively.) Conclusion The flowchart will be intuitive and helpful to instruct appropriate use of RMST based and traditional methods. RMST-based methods provided an absolute effect measure to inspect effects of covariates on survival time and promote evidence communication with HR. Difference in RMST should be reported with hazard ratio routinely.

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“…A prospective cohort study exploring the relationship between midlife cardiorespiratory tness and chronic obstructive pulmonary disease performed both Cox models and RMST analysis, estimated HR and changes in RMST of incidence of COPD and presented death simultaneously, which increased the reliability and understandability of the conclusion [16]. In addition to original studies, RMST and difference in RMST have been considered as effect measures in metaanalysis [17,18]. RMST was regarded as an obligatory end point, while HR and difference in RMST as complementary methods to summarize treatment effect in oncological trials [19].…”

Section: Discussionmentioning

confidence: 99%

A univariable and multivariable analysis of right censored time-to-event data based on restricted mean survival time: A combination with traditional survival methods.

Lyv

Deng

et al. 2020

Preprint

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Background: Many traditional survival analyses and restricted mean survival time (RMST) based analyses have been proposed for dealing with right censored time-to-event data. It is necessary to sort out the conditions and relationship among these methods for instruction. Comparison between hazard ratio (HR) and RMST in a study may promote appropriate understanding and application of the two effect measures.Method : Traditional survival analyses and RMST-based analyses were integrated into a flowchart and applied for univariable and multivariable analyses, RMST-based analyses included group comparison for difference in RMST, pseudo-value (PV) regressions, inverse probability of censoring probability (IPCW) regressions with group-specific weights and individual weights with homogeneity of censoring mechanism assumption. 4405 osteosarcomas were captured from Surveillance, Epidemiology and End Results Program Database. HR and difference in RMST (survival time lost or gain, STL or STG) were considered as effect measures and the effect of all included covariates on overall survival were reported for comparison. The relationship between difference in RMST and HR were explored when proportional hazard (PH) assumption was and was not met, respectively. Results: In group comparison and univariable regressions, using difference in RMST calculated by Kaplan-Meier methods as reference, PV regressions (R2=0.99) and IPCW regressions with group-specific weights (R2=1.00) provided more consistent estimation on difference in RMST than IPCW with individual weights (R2=0.09). In multivariable analysis, age (HR:1.03, STL: 3.86 months), diagnosis in 1970~1980s (HR:1.39 STL:27.49 months), metastasis (HR:4.47, STL: 202 months), surgery (HR:0.58, SLG:35.55 months) and radiation (HR:1.46, SLT:44.65 months) met PH assumption and were main independent factors for overall survival. In both univariable and multivariable variables, a robust negative logarithmic linear relationship between HRs estimated by Cox regression and differences in RMST by pseudo-value regressions was only observed when PH assumption was hold. Conclusion: The flowchart may be intuitive and helpful to instruct appropriate use of RMST based and traditional methods. PH assumption and homogeneity of censoring mechanism assumption will determine the appropriate selection of these method. HR and difference in RMST can be reported comprehensively.

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Programmed Death-1 or Programmed Death Ligand-1 Blockade in Patients with Platinum-resistant Metastatic Urothelial Cancer: A Systematic Review and Meta-analysis

Cited by 43 publications

References 30 publications

Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody–Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma

Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody–Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma

A univariable and multivariable analysis of time-to-event data based on restricted mean survival time: A combination with traditional survival methods.

A univariable and multivariable analysis of right censored time-to-event data based on restricted mean survival time: A combination with traditional survival methods.

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