ASCO 2022: Long-Term Outcomes in Patients with Advanced Urothelial Carcinoma (UC) Who Received Avelumab First-Line Maintenance with or Without Second-Line Treatment: Exploratory Analyses from JAVELIN Bladder 100

( At the 2022 American Society of Clinical Oncology Annual Meeting held in Chicago and virtually, the poster session focused on Kidney and Bladder cancers on Saturday afternoon included a presentation from Dr. Joaquim Bellmunt examining long-term outcomes from the JAVELIN Bladder 100 trial among patients receiving first-line avelumab maintenance therapy, with a specific focus on the use of subsequent second-line therapy.

The phase 3 JAVELIN Bladder 100 trial (NCT02603432) demonstrated that first-line avelumab maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) compared to BSC alone in patients with advanced urothelial carcinoma (UC) that had not progressed during initial induction treatment with platinum-based chemotherapy (median OS, 23.8 vs 15.0 months; HR, 0.76 [95% CI, 0.631-0.915]; 2-sided p = 0.0036).

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As a result, this approach has now become standard of care in international guidelines. However, outcomes among patients who receive subsequent second line therapy following avelumab maintenance are limited. Thus, the authors performed a descriptive analysis focused on patients in the intervention arm of the JAVELIN Bladder 100 trial.

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While previously published, to briefly recap, JAVELIN Bladder 100 included patients with unresectable locally advanced or metastatic UC without progression after 4-6 cycles of first-line gemcitabine + cisplatin or carboplatin. Following their initial chemotherapy course, patients were randomized in a 1:1 fashion to receive avelumab + BSC (n = 350) or BSC alone (n = 350). Randomization was stratified two-fold: by best response to first-line chemotherapy (CR/PR vs SD) and by the presence of visceral (vs nonvisceral disease) at start of chemotherapy. In this abstract, the authors describe exploratory analyses examining the time from randomization to end of second-line treatment and overall survival among patients in the avelumab + BSC arm, with subgroups defined by non-protocol directed second-line treatment administered by investigators after discontinuation of study treatment.

With a data cutoff of June 4, 2021, the median follow-up was 38.0 months among the patients in the avelumab + BSC arm (n = 350). At this time, the majority (n=185; 52.9%) had discontinued avelumab first-line maintenance treatment for any reason and had received second-line treatment, whereas 122 (34.9%) had discontinued avelumab without receiving subsequent second-line treatment. The remaining 43 patients (12.3%) remained on avelumab maintenance therapy. In this subset, the median treatment duration was 154.6 weeks (range, 106.7-216.0).

Among those who received second-line treatment, median time from end of avelumab maintenance to start of second-line treatment was 1.35 months (range, 0.3-30.9) and median time from randomization to end of second-line treatment was 11.7 months (95% CI, 9.7-13.8). A variety of treatment approaches were used including rechallenge with platinum-based chemotherapy in 75 (21.4%) or other 2L treatment in 110 (31.4%), including second-line anti–PD-(L)1 therapy in 11 (3.1%).

Median overall survival was not reach among those receiving ongoing avelumab maintenance whereas it was 19.9 months (95% CI 18.2-23.0) among those who received second-line therapy following avelumab maintenance and 18.2 months (95% CI 10.0-34.4) among those who did not.

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Thus, the authors concluded that this exploratory analysis of the JAVELIN Bladder 100 trial shows the second-line treatment is common following avelumab maintenance therapy. Long-term overall survival may be observed with or without second-line treatment.

Presented by: Joaquim Bellmunt, MD, PhD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA