ESMO 2023: Avelumab First-Line Maintenance for Locally Advanced or Metastatic Urothelial Carcinoma (la/mUC): Treatment Patterns and Real-World Outcomes in the US

(UroToday.com) The 2023 European Society of Medical Oncology (ESMO) Annual Congress held in Madrid, Spain between October 20^th and 24^th, 2023 was host to a urothelial cancer abstracts poster session. Dr. Kenneth Carson presented the results of a US-based, real-world study of avelumab 1^st line maintenance for patients with locally advanced or metastatic urothelial carcinoma.

In June 2020, the US Food and Drug Administration (FDA) approved avelumab for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that had not progressed with 1^st line platinum-containing chemotherapy. This approval followed the initial results of the JAVELIN-100 trial that demonstrated an overall survival improvement from 14.3 months in the best supportive care arm to 21.4 months in the avelumab + best supportive care arm (HR: 0.69, 95% CI: 0.56 to 0.86, p=0.001).¹ As such, avelumab maintenance has become guideline recommended in this setting.

Despite the publication of level one evidence for avelumab in patients with advanced urothelial carcinoma, there is often a discord between clinical trials and real-world outcomes. Reasons for such discrepancies include patients in clinical trials classically being healthier patients with superior performance status and easier access to 2^nd line, salvage therapies. Furthermore, clinical trials often have strict eligibility criteria that limit the external generalizability/validity of the study results. As such, real world data for avelumab, and other approved drugs in the advanced cancer disease space, are of utmost importance. The objective of this study was to describe real-world outcomes in patients with locally advanced or metastatic urothelial carcinoma receiving 1^st line avelumab maintenance.

This study included patients with locally advanced/metastatic urothelial carcinoma diagnosed between January 2016 and March 2023, identified through the Tempus database. Patients who completed 1^st line platinum-based chemotherapy after avelumab’s FDA approval in June 2020 were considered eligible for 1^st line maintenance. 1^st line maintenance was differentiated from 2^nd line treatment based on clinical intent documentation or determined algorithmically based on initiation of immuno-oncology treatment within 180 days of 1^st line platinum-based chemotherapy without recorded disease progression. The study outcomes of overall survival (OS), progression-free survival, time on treatment, and time to next treatment were estimated using Kaplan Meier estimates.

3,299 patients were identified, of whom 1,939 (59%) received 1^st line systemic therapy. The median age at diagnosis was 70 years, 74% were male, 85% were White, 88% had urothelial carcinoma, and 48% had a documented smoking history. Of the 1,939 patients, 974 (50.2%) completed 1^st line therapy, with platinum-based chemotherapy the most common 1^st line regimen (66%). The median follow-up from the start of 1^st line platinum-based chemotherapy was 10.2 months. The median OS was 13.6 months.

Of the 644 patients receiving 1^st line platinum-based chemotherapy, 89% had no evidence of disease progression following treatment completion, 38% of whom had received 1^st line maintenance, most commonly with avelumab (62%). These patients had a median follow-up from 1^st line maintenance start of 8.9 months. Real world OS landmark analysis from 1^st line maintenance initiation demonstrated that 80% of avelumab 1^st line maintenance patients were still alive at 6 months and 63% were alive at 12 months. The median PFS from 1^st line maintenance start was 6.4 months and the median time on treatment was 3.85 months. After 1^st line maintenance avelumab, 35% of patients received 2^nd line treatment. 70% of those received enfortumab vedotin, with a median OS from start of 2^nd line treatment of just under 12 months.

Dr. Carson concluded that early uptake of avelumab 1^st line maintenance was observed in patients with locally advanced/metastatic urothelial carcinoma whose disease had not progressed on 1^st line platinum-based chemotherapy. Given that the follow-up time on avelumab treatment was relatively short in this study, future studies with longer follow-up may show increased use and allow for further assessment of real-world outcomes.

1. Powles T, Park SH, Voog E, et al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med 2020 Sept 24;383(13):1218-1230.