ASCO 2021: Avelumab First-Line Maintenance for Advanced Urothelial Carcinoma: Analysis of Clinical and Genomic Subgroups from the JAVELIN Bladder 100 Trial

(UroToday.com) In the phase 3 JAVELIN Bladder 100 trial, avelumab first-line maintenance + best supportive care significantly prolonged overall survival versus best supportive care alone in patients with advanced urothelial carcinoma that had not progressed on first-line platinum-based chemotherapy (HR 0.69, 95% CI 0.56 to 0.86; 1-sided p = 0.0005).1 Based on these results, avelumab first-line maintenance was approved in the USA, Canada, Europe, Japan, etc for patients who are progression-free following platinum-based chemotherapy. At the 2021 American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, Dr. Thomas Powles and colleagues presented results of post hoc analyses in previously unreported clinical and genomic subgroups.


In JAVELIN Bladder 100, eligible patients had unresectable locally advanced or metastatic urothelial carcinoma without progression after 4-6 cycles of first-line gemcitabine + cisplatin or carboplatin and were randomized to receive avelumab + best supportive care (n = 350) or best supportive care alone (n = 350). The primary endpoint was overall survival (OS), in all randomized patients and patients with PD-L1+ tumors using the Ventana SP263 assay. In this exploratory analysis, Dr. Powles and colleagues analyzed OS in disease stage and site subgroups, in patients with PD-L1+ tumors who received first-line gemcitabine + carboplatin, and in genomic subtypes (RNAseq whole-transcriptome profiling of tumor tissue) defined using data from The Cancer Genome Atlas (TCGA 2017). Progression-free survival was assessed as a secondary endpoint.

Prolonged OS was observed in the avelumab + best supportive care arm versus the best supportive care alone arm in patients with upper or lower tract tumors, metastatic or locally advanced and unresectable disease (prior to chemotherapy), and lymph node-only disease post-chemotherapy. OS was also prolonged with avelumab + best supportive care in patients in PD-L1+ tumors who had received 1L gemcitabine + carboplatin, consistent with findings in the overall population:

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A similar trend seen in the OS analysis was reported for PFS:

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In genomic subtypes, the OS benefit for avelumab + best supportive care was apparent across TCGA subtypes except luminal:

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Dr. Powles concluded his presentation of posthoc analysis of the JAVELIN Bladder 100 trial with the following take-home messages:

  • An OS and PFS benefit was seen for avelumab first-line maintenance + best supportive care versus best supportive care alone across subgroups of interest, including patients with upper or lower tract disease, metastatic disease, unresectable locally advance disease, or lymph node-only disease, PD-L1 positive tumors who received first-line gemcitabine + carboplatin, and tumor genomic subtypes defined by the TCGA (except luminal)
  • Results are consistent with previously reported findings, further supporting avelumab first-line maintenance as a standard of care for patients with advanced urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy

Clinical trial information: NCT02603432

Presented by: Thomas Powles, MBBS, MRCP, MD, Professor of Genitourinary Oncology, Lead for Solid Tumour Research at Barts Cancer Institute, Director of Barts Cancer Institute, London, United Kingdom

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

References:

  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.