Benchmarking Maintenance Therapy Survival in First-Line Platinum-Based Chemotherapy–Treated Patients with Advanced Urothelial Carcinoma Using Simulated Disease Modeling

Figures & data

Figure 1 Comparison of the design of an oncology maintenance therapy trial with a traditional 1L oncology therapy trial. Common 1L oncology clinical trial designs measure OS from initiation of 1L therapy at randomization. Bladder cancer maintenance clinical trial designs^4,20 measure OS from initiation of maintenance therapy, a period of time after the initiation of 1L therapy in those patients who had no disease progression after 1L chemotherapy (nonprogressors). Comparing these two trial designs is a controversial issue and has been described in a recent publication.²¹

Abbreviation: 1L, first line.

Table 1 Summary of Known and Unknown Data in the 1L PBT–Treated, Maintenance Avelumab–Intended Population of Patients with aUC

Patient Population	Clinical Outcome/ Population Characteristic	Known/Unknown in Published Literature
Maintenance avelumab–eligible, received maintenance	mOS^a	Known (JAVELIN avelumab arm^Citation4)
	Proportion of total 1L PBT–treated, maintenance avelumab–intended population	Unknown
Maintenance avelumab–eligible, did not receive maintenance	mOS^b	Known (JAVELIN BSC arm^Citation4)
	Proportion of total 1L PBT–treated, maintenance avelumab–intended population	Unknown
Maintenance avelumab–ineligible	mOS	Unknown
	Proportion of total 1L PBT–treated, maintenance avelumab–intended population	Unknown

Notes: ^amOS measured from point of randomization to maintenance avelumab; ^bReported mOS represents the population who responded to 1L PBT treatment.

Abbreviations: 1L, first-line; aUC, advanced urothelial carcinoma; BSC, best supportive care; mOS, median overall survival; PBT, platinum-based therapy.

Figure 2 Estimated OS in 1L PBT maintenance–intended patients with aUC from initiation of 1L PBT. (A) OS in maintenance eligible, received maintenance from the JAVELIN active arm (green), OS in maintenance eligible, did not receive maintenance from the JAVELIN BSC arm (yellow), and the estimated OS in maintenance ineligible (red) were used to calculate (B) the combined OS in the 1L PBT–treated, maintenance-intended patient population (black) by calculating the weighted average hazard of the three subgroups.⁴

Note: ^aIncludes 5.6-month run-in period.

Abbreviations: 1L, first-line; aUC, advanced urothelial carcinoma; BSC, best supportive care; mOS, median overall survival; PBT, platinum-based therapy; TFI, treatment-free interval.

Figure 3 Contour plot of population-level OS impact across included clinical trials.^4,13,15,16 By varying the proportion of the 1L PBT maintenance-intended population that received maintenance (x-axis) and varying the mOS associated with PBT between 12.0 and 15.0 months (y-axis), the survival benefit from maintenance compared with PBT alone (based on OS data from the KEYNOTE-361,¹³ IMvigor130,¹⁵ and DANUBE¹⁷ clinical trials) ranged from 2 to 8 weeks (shown in colored bands). mOS for included clinical trials is shown by the dotted lines. The red dot highlights the expected survival benefit of 2 weeks based on PBT control-arm data from DANUBE¹⁷ if 22.5% of eligible patients received maintenance avelumab. (The green dot highlights the expected survival benefit of 4 weeks based on PBT control-arm data from IMvigor130¹⁵ if 36% of eligible patients received maintA. The yellow dot highlights the expected survival benefit of 6 weeks based on PBT control-arm data from KEYNOTE-361¹³ if 46% of eligible patients received maintenance (compared with 5 weeks from IMvigor130¹⁵ and 4 weeks from DANUBE¹⁷).

Abbreviations: 1L, first-line; mOS, median overall survival; OS, overall survival; PBT, platinum-based therapy.

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