ASCO 2021: Avelumab First-Line Maintenance for Advanced Urothelial Carcinoma in the JAVELIN Bladder 100 Trial: Subgroup Analysis by Duration of Treatment-Free Interval from End of Chemotherapy to Start of Maintenance

( The phase 3 JAVELIN Bladder 100 trial, which enrolled patients with advanced urothelial carcinoma that had not progressed with first-line platinum-containing chemotherapy, showed that maintenance therapy with avelumab + best supportive care significantly prolonged overall survival (OS) compared with best supportive care alone (HR 0.69, 95% CI 0.56 to 0.86; 1-sided p = 0.0005).1 However, the optimal timing for starting avelumab after completing first-line chemotherapy is unknown. In the trial, patients received avelumab + best supportive care or best supportive care alone after a treatment-free interval of 4 to 10 weeks from completion of first-line treatment in order to allow resolution of any chemotherapy-related toxicities and tumor assessment to confirm eligibility. At the 2021 American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, Dr. Srikala Sridhar and colleagues presented results of a post hoc analysis assessing efficacy by duration of the treatment-free interval from completion of first-line chemotherapy.

In the JAVELIN Bladder 100 trial, eligible patients had unresectable locally advanced or metastatic urothelial carcinoma without disease progression following 4 to 6 cycles of first-line platinum-containing chemotherapy. Patients were randomized to receive avelumab + best supportive care (n = 350) or best supportive care alone (n = 350) after a treatment-free interval of 4 to 10 weeks from the last dose of chemotherapy. In this exploratory analysis, subgroups with a treatment-free interval of 4 to < 6 weeks (< 42 days), 6 to < 8 weeks (42 to < 56 days), or 8 to 10 weeks (≥56 days) were evaluated.

In the avelumab + best supportive care and best supportive care alone arms, the treatment-free interval was 4 to < 6 weeks in 143 and 158 patients, 6 to < 8 weeks in 109 and 80 patients, and 8 to 10 weeks in 98 and 110 patients, respectively. Baseline characteristics in these subgroups were generally well balanced between arms. For both arms combined, however, the treatment-free interval 4 to < 6 weeks subgroup versus the other 2 subgroups included more patients with visceral metastases (57.8% vs 54.0% and 50.0%), an objective response with first-line chemotherapy (76.4% vs 69.3% and 68.3%), and an ECOG performance status of 1 (44.5% vs 33.3% and 35.6%). Baseline characteristics in the treatment-free interval subgroups are summarized as follows:


OS was prolonged with avelumab + best supportive care versus best supportive care alone in all subgroups. The HR was 0.76 (95% CI: 0.546, 1.059) in the treatment-free interval 4 to < 6 weeks subgroup (median OS, 19.9 months [95% CI: 16.3, 25.3] vs 13.5 months [95% CI: 11.7, 17.4]):


0.64 (95% CI: 0.404, 1.021) in the treatment-free interval 6 to < 8 weeks subgroup (median OS, 26.1 months [95% CI: 19.9, not estimable] vs 21.0 months [95% CI: 10.7, not estimable]):


and 0.70 (95% CI: 0.468, 1.035) in the treatment-free interval 8 to 10 weeks subgroup (median OS, 20.1 months [95% CI: 13.8, not estimable] vs 14.1 months [95% CI: 11.7, 19.6]):


The safety profile of avelumab first-line maintenance was generally similar between subgroups, irrespective of the length of treatment-free interval before starting maintenance.

Dr. Sridhar concluded this subgroup analysis of the JAVELIN Bladder 100 trial with the following concluding statements:

  • In patients with advanced urothelial carcinoma that had not progressed with first-line platinum-containing chemotherapy, avelumab first-line maintenance prolonged OS irrespective of the treatment-free interval assessed in this study (4-10 weeks), supporting this new treatment strategy as a standard of care
  • Differences in duration of treatment-free interval were likely related to the individual patient- and disease-specific characteristics or logistics and did not impact the OS benefit observed with avelumab first-line maintenance

Clinical trial information: NCT02603432

Presented by: Srikala Sridhar MD, MSc, FRCPC, Associate Professor, Department of Medicine, Division of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021


  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.

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