(UroToday.com) The 2024 American Urological Association (AUA) annual meeting featured a session on invasive bladder cancer, and a presentation by Dr. Shilpa Gupta discussing long-term outcomes from JAVELIN Bladder 100 in subgroups defined by first-line chemotherapy regimen and analysis of overall survival from start of first-line chemotherapy. In the phase 3 JAVELIN Bladder 100 trial, avelumab first-line maintenance + best supportive care significantly prolonged overall survival and progression-free survival from start of maintenance (randomization) vs best supportive care alone in patients with advanced urothelial carcinoma without progression after first-line platinum-based chemotherapy (median overall survival, 23.8 vs 15.0 months; HR 0.76, 95% CI, 0.63-0.91; p = 0.0036).1 Moreover, long term safety of maintenance avelumab was demonstrated with no new safety signals. At AUA 2024, Dr. Gupta and colleagues reported post hoc analyses of long-term outcomes by first-line chemotherapy and overall survival from start of first-line chemotherapy.
Patients with unresectable locally advanced or metastatic urothelial carcinoma without progression after 4-6 cycles of first-line cisplatin or carboplatin + gemcitabine were enrolled (n = 700). The trial design for JAVELIN Bladder 100 is as follows:
The primary endpoint was overall survival measured from randomization.
When stratified by type of chemotherapy received (cisplatin + gemcitabine vs carboplatin + gemcitabine), baseline characteristics were well balanced between those receiving avelumab + best standard of care vs best standard of care alone:
At the data cutoff (June 4, 2021), median follow-up from randomization was ≥38 months in both arms. In subgroups treated with first-line cisplatin + gemcitabine or carboplatin + gemcitabine, overall survival from the start of avelumab was longer with avelumab + best supportive care vs best supportive care alone:
Investigator assessed progression free survival was also longer in the avelumab + best supportive care versus best supportive care alone in both subgroups: 5.7 months vs 2.0 months, HR 0.56, 95% CI 0.446-0.713 (cisplatin + gemcitabine); 3.7 months vs 2.0 months, HR 0.48, 95% CI 0.362-0.640 (carboplatin + gemcitabine). In the overall population, median overall survival measured from the start of first-line chemotherapy in this population without progression after first-line chemotherapy was 29.7 months (95% CI 25.2-34.0) with avelumab + best supportive care and 20.5 months (95% CI 19.0-23.5) with best supportive care alone (HR 0.77, 95% CI 0.635-0.921):
Assessing overall survival measured from the start of first-line chemotherapy stratified by type of chemotherapy received showed no benefit for avelumab maintenance in the cisplatin + gemcitabine subgroup (HR 0.79, 95% CI 0.613-1.024), but did show benefit for avelumab maintenance in the carboplatin + gemcitabine subgroup (HR 0.69, 95% CI 0.514-0.920):
Long term safety findings were similar in both subgroups:
Dr. Gupta concluded her presentation by discussing long-term outcomes from JAVELIN Bladder 100 in subgroups defined by first-line chemotherapy regimen with the following take-home messages:
- Long-term outcomes from JAVELIN Bladder 100 confirm that avelumab first-line maintenance provides similar overall survival and progression-free survival benefits in patients with advanced urothelial carcinoma without progression after first-line cisplatin- or carboplatin-based chemotherapy
- Long-term safety of first-line avelumab maintenance was similar in patients who had received first line cisplatin or carboplatin based chemotherapy
- The median overall survival measured from start of chemotherapy (median 29.7 months) further supports the use of avelumab first-line maintenance as standard of care in this setting and provides a benchmark for future clinical trials
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 2024 American Urological Association (AUA) Annual Meeting, San Antonio, TX, Fri, May 3 – Mon, May 6, 2024.
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.