ESMO 2024: Avelumab First-Line Maintenance in Advanced Urothelial Carcinoma: Conditional Survival and Long-Term Safety in Patients Treated for ≥1 or ≥2 Years in JAVELIN Bladder 100

(UroToday.com) The 2024 ESMO annual meeting included a session on urothelial carcinoma, featuring a presentation by Dr. Petros Grivas discussing conditional survival and long-term safety in patients treated for ≥1 or ≥2 years in the JAVELIN Bladder 100 trial. In the JAVELIN Bladder 100 phase 3 trial (NCT02603432), avelumab first-line maintenance + best supportive care significantly prolonged overall survival and progression-free survival vs best supportive care alone in patients with advanced urothelial carcinoma that had not progressed with first-line platinum-based chemotherapy.¹

Results from the trial supported the inclusion of avelumab as first-line maintenance in updated international treatment guidelines as a recommended treatment option for patients with advanced urothelial carcinoma. At ESMO 2024, Dr. Grivas and colleagues reported conditional survival estimates and safety in patients treated with avelumab for ≥1 or ≥2 years.

Eligible patients with unresectable locally advanced or metastatic urothelial carcinoma without progression after first-line platinum-based chemotherapy were randomized 1:1 to receive avelumab + best supportive care (n = 350) or best supportive care alone (n = 350). The primary endpoint was overall survival (from randomization), and secondary endpoints included progression-free survival and safety. The trial design for JAVELIN Bladder 100 is as follows:

In this post hoc analysis, subgroups of patients who had been treated with avelumab for >= 1 or >=2 years were analyzed.

At a data cutoff (June 4, 2021), median follow-up in the avelumab + best supportive care arm was 38.0 months (>= 2 years in all patients). Among 350 patients randomized to avelumab + best supportive care, treatment duration was ≥1 year in 118 patients (34.3%) and ≥2 years in 68 (19.8%). Compared with the overall avelumab + best supportive care arm, a higher proportion of patients with ≥2 years of treatment had received first-line gemcitabine + cisplatin (64.7% vs 52.3%), had non-visceral metastases (58.8% vs 45.4%), and had PD-L1+ tumors (64.7% vs 54.0%):
In patients who received ≥1 year of treatment, the probability of surviving for an additional 1 or 2 years was 93.2% and 79.6%, respectively:
In this subgroup, the probability of surviving for an additional 6 months or 1 year without progression was 77.9% and 66.7%, respectively:
In patients who received ≥2 years of treatment, the probability of surviving for an additional 1 or 1.5 years was 95.8% and 90.3%, respectively:
In this subgroup, the probability of surviving an additional 6 months or 1 year without progression was 82.9% and 66.7%, respectively:

In patients who were still receiving avelumab treatment at specified time points, rates of adverse events and treatment-related adverse events over time is highlighted in the following table:

Any grade treatment-related adverse events occurred after 1 year in 50.0% of patients and after 2 years in 35.3%, including grade ≥3 treatment-related adverse events in 11.9% and 5.9%, respectively. In general, types of treatment-related adverse events that occurred after 1-2 years of treatment were consistent with those observed in the overall population:
Dr. Grivas concluded his presentation discussing conditional survival and long-term safety in patients treated for ≥1 or ≥2 years in the JAVELIN Bladder 100 trial with the following take-home points:

• This post hoc analysis from the JAVELIN Bladder 100 phase 3 trial examined the probability of additional overall survival, progression-free survival, and safety in patients with advanced urothelial carcinoma that has not progressed with first-line platinum-based chemotherapy who received >=1 or >= 2 years of avelumab first-line maintenance treatment
• In patients who had received 1 year of avelumab treatment (34%), the probability of an additional 1-2 years of overall survival was 93.2% and 79.6%, respectively.
• In patients who had received 2 years of avelumab treatment (19.8%), the probability of an additional 1 or 1.5 years of overall survival was 95.8% and 90.3%, respectively.
• Patients who had 1 or 2 years of avelumab treatment also had a high probability (66.7%) of having an additional 1 year of progression-free survival
• In patients still receiving treatment, rates of grade ≥3 treatment-related adverse events occurring after 1 or 2 years were low (11.9 vs 5.9%, respectively)
• Overall these results inform prognosis and show that patients with advanced urothelial carcinoma without progression after first-line platinum-based chemotherapy who survive for ≥1 or ≥2 years while receiving avelumab first-line maintenance treatment have a high probability of additional years of overall survival, with low rates of grade ≥3 treatment-related adverse events.

Presented by: Petros Grivas, MD, PhD, Associate Professor, Department of Medicine, Division of Oncology, Clinical Director, Genitourinary Cancers Program, Fred Hutch Cancer Center, University of Washington Medicine, Seattle, WA

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 European Society of Medical Oncology (ESMO) Annual Meeting, Barcelona, Spain, Fri, Sept 13 – Tues, Sept 17, 2024. 

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.