Survival Outcomes and Parameters of Switch Maintenance - Expert Commentary
This was confirmed in the phase 3 JAVELIN Bladder 100 trial, in which improved survival was observed in patients with advanced urothelial carcinoma who received four to six cycles of first-line platinum-based chemotherapy followed by avelumab maintenance and best supportive care (BSC). Sridhar et al. analyze data from JAVELIN to identify recommendations for the duration and number of cycles of chemotherapy and the duration between the end of chemotherapy and the start of maintenance therapy.
The JAVELIN cohort consisted of 700 patients, 350 of whom received avelumab and BSC and 350 of whom received BSC alone. Patients were divided into subgroups based on the duration of first-line chemotherapy as follows: <Q1: less than 15.0 weeks (n=171); Q1-Q2: 15.0 to 18.0 weeks (n=145); Q2-Q3: 18.0 to 20.1 weeks (n=211); and >Q3: more than 20.1 weeks (n=171). In the <Q1 subgroup, median overall survival (OS) was 18.9 months in the avelumab arm and 13.0 months in the control arm (HR, 0.65; 95% CI, 0.42–1.02), while median progression-free survival (PFS) was 3.5 months and 1.9 months, respectively (HR, 0.71; 95% CI, 0.49–1.02). In the Q1–Q2 subgroup, the median OS was 19.9 months in the avelumab arm and 15.5 months in the control arm (HR, 0.79; 95% CI, 0.50–1.27), and median PFS was 5.6 months and 1.9 months, respectively (HR, 0.57; 95% CI, 0.37–0.86). In the Q2–Q3 subgroup, the median OS was 19.2 months in the avelumab arm and 14.3 months in the control arm (HR, 0.74; 95% CI, 0.50–1.10), and the median PFS was 3.6 months and 1.9 months, respectively (HR, 0.68; 95% CI, 0.49–0.94). In the >Q3 subgroup, the median OS was 24.0 months in the avelumab arm and 17.9 months in the control arm (HR, 0.63; 95% CI, 0.39–1.00), and the median PFS was 5.6 months and 3.5 months, respectively (HR, 0.55; 95% CI, 0.37–0.80). Among patients who received four cycles (n=251), the median OS was 19.9 months in the avelumab arm and 13.7 months in the control arm (HR, 0.69; 95% CI, 0.48–1.00), and the median PFS was 3.8 and 2.0 months, respectively (HR, 0.59; 95% CI, 0.43–0.80). In patients who received five cycles of treatment (n=113), the median OS was 19.9 months in the avelumab arm and 17.8 months in the control arm (HR, 0.98; 95% CI, 0.57–1.71), and the median PFS was 2.4 and 2.1 months, respectively (HR, 0.77; 95% CI, 0.48–1.22). Among patients who received six cycles (n=298), the median OS was 24.0 months in the avelumab arm and 14.0 months in the control arm (HR, 0.66; 95% CI, 0.47–0.92), and the median PFS was 3.7 months and 1.9 months, respectively (HR, 0.60; 95% CI, 0.45–0.79). Among patients with a 4-to-6-week period between completion of chemotherapy and the start of maintenance therapy (n=301), median OS was 19.9 months in the avelumab arm and 13.5 months in the control arm (HR, 0.75; 95% CI, 0.54–1.04) while median PFS was 3.7 months and 1.9 months, respectively (HR, 0.68; 95% CI, 0.51–0.90). In the 6-to-8-week subgroup (n=189), the median OS was 26.1 months in the avelumab arm and 21.0 months in the control arm (HR, 0.67; 95% CI, 0.43–1.06) and the median PFS was 3.7 months and 1.9 months, respectively (HR, 0.57; 95% CI, 0.39–0.82). In the 8-to-10-week subgroup (n=208), the median OS was 20.1 months in the avelumab arm and 14.1 months in the control arm (HR, 0.69; 95% CI, 0.47–1.02) and the median PFS was 3.8 months and 3.4 months, respectively (HR, 0.62; 95% CI, 0.44–0.86).
Overall, none of the investigated variables significantly affected patient survival. The investigators concluded that treatment plans should be tailored to patient needs, but the optimal number of chemotherapy cycles appears to be between four and six. In addition, it is not recommended to exceed a 10-week interval before initiation of maintenance therapy.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine
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