(UroToday.com) The 2023 ESMO annual meeting included a session on urothelial carcinoma, featuring a presentation by Dr. Shilpa Gupta discussing long-term outcomes from the JAVELIN Bladder 100 trial in older patients. In the phase 3 JAVELIN Bladder 100 trial, avelumab first line maintenance therapy + best supportive care significantly prolonged overall survival (OS) and progression-free survival (PFS) vs best supportive care alone in patients with advanced urothelial carcinoma without progression following first line platinum-based chemotherapy.1
After ≥2 years of follow-up in all patients, median OS was 23.8 months (95% CI, 19.9-28.8) vs 15.0 months (95% CI, 13.5-18.2), respectively.2 Importantly, avelumab first line maintenance also had minimal impact on quality of life. Results from this trial led to the recommendation of avelumab first line maintenance as standard of care for patients with advanced urothelial carcinoma who are progression free after first line platinum-based chemotherapy in international treatment guidelines. Older age is a key risk factor for urothelial carcinoma, with a median age at diagnosis of 73 years, which is important as >90% of patients with urothelial carcinoma are aged ≥ 55 years when diagnosed. Additionally, increasing age may also be associated with declining immune function and only a small proportion of older patients receive systemic treatment. At ESMO 2023, Dr. Gupta and colleagues report long-term efficacy and safety outcomes in subgroups based on older age (≥ 65 years).
Eligible patients with locally advanced or metastatic urothelial carcinoma without progression following 4 to 6 cycles of 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 OS, and secondary endpoints included PFS and safety. For this post hoc analysis, subgroups aged ≥65 to <75 years, ≥75 years, and ≥80 years were analyzed, and patients aged <65 years were not included in this analysis.
At the time of data cutoff (June 4, 2021), the median follow-up was 38.0 months in the avelumab + best supportive care versus 39.6 months in the best supportive care alone arm. In the avelumab + best supportive care and best supportive care alone arms, age was ≥65 to <75 years in 136 and 163 patients, ≥75 years in 85 and 80 patients, and ≥80 years in 28 and 27 patients, respectively. Baseline characteristics are as follows:
In all subgroups defined by older age, OS was prolonged in the avelumab + best supportive care arm versus the best supportive care alone arm:
Investigator assessed PFS was also prolonged with avelumab + best supportive care versus best supportive care alone in all older subgroups:
The long-term safety of avelumab first line maintenance was acceptable in all older age subgroups and was comparable to the safety profile in the overall population:
Two patients (2.4%) in the ≥ 75 years subgroup, of which one patient was aged ≥ 80 years, had a treatment-related adverse event that led to death (sepsis and attributed to immune-related nephritis by treating investigator).
Dr. Gupta concluded her presentation discussing long-term outcomes from the JAVELIN Bladder 100 trial in older patients with the following concluding statements:
- Long-term outcomes from JAVELIN Bladder 100 confirm prolonged OS and PFS with avelumab + best supportive care versus best supportive care alone in older patients
- The long-term safety of avelumab first line maintenance was similar across subgroups, confirming its tolerability
- These findings provide further support for avelumab first line maintenance as standard of care in patients with advanced urothelial carcinoma without progression following first line platinum-based chemotherapy, including older patients over 65 years old
Presented by: Shilpa Gupta, MD, Cleveland Clinic Foundation, Cleveland, OH
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Meeting, Madrid, Spain, Fri, Oct 20 – Tues, Oct 24, 2023.
References:
- 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.
- Powles T, Park SH, Caserta C, et al. Avelumab First-Line Maintenance for Advanced Urothelial Carcinoma: Results From the JAVELIN Bladder 100 Trial After >/=2 Years of Follow-Up. J Clin Oncol. 2023;41: 3486-3492.