ASCO 2022: Avelumab First-Line (1L) Maintenance for Advanced Urothelial Carcinoma (aUC): Long-Term Outcomes from JAVELIN Bladder 100 in Subgroups Defined by Response to 1L Chemotherapy

(UroToday.com) 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. Begona Perez-Valderrama examining long-term outcomes from the JAVELIN Bladder 100 trial among patients receiving first-line avelumab maintenance therapy, with stratification according to response to first-line induction chemotherapy.


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.

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However, this is a somewhat heterogeneous group including those with a complete response [CR], partial response [PR], or stable disease [SD]. Thus, the authors sought to perform exploratory analyses in these subgroups with more than 2 years of follow-up.

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.

As of a data cutoff of June 4, 2021, the median follow-up in both arms exceeded 38 months. Across all subgroups defined based on their response to first-line chemotherapy, overall survival and progression-free survival were prolonged among those patients who received avelumab maintenance.

The median duration of study therapy among those randomized to avelumab was longer for patients who had an initial CR (33.8 weeks, range 2.0-214.4) than those with a PR (22.2 weeks, range 2.0-213.1) or SD (25.1 weeks, range 2.0-216.0).

In terms of overall survival, benefits of the use of avelumab maintenance therapy were seen in patients with a complete response (HR 0.72, 95% CI 0.48-1.08), an initial partial response (hr 0.70, 95% ci 0.54-0.91), or initially stable disease (HR 0.84, 95% CI 0.60-1.19).

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Overall, grade 3 or higher adverse events were seen more often in patients randomized to avelumab though this did not differ substantially between the groups. Of note, among patients randomized to placebo + BSC, serious adverse events were more common in those with SD than with CR or PR.

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In the avelumab + BSC vs BSC alone arm, respectively, subsequent second-line anticancer drug therapy was received by: CR subgroup, 50.0% vs 74.2%; PR subgroup, 58.3% vs 71.8%; and SD subgroup, 46.4% vs 70.4%.

Thus, the authors conclude that this long-term follow-up from JAVELIN Bladder 100 continues to demonstrate a survival benefit to the addition of avelumab maintenance therapy to BSC, independent of response (CR, PR, or SD) to first-line chemotherapy. This effect was observed despite a higher proportion of pts in the BSC alone arm receiving subsequent therapy.

Presented by: Begona Perez-Valderrama, Hospital Universitario Virgen del RocĂ­o