ASCO GU 2023: Avelumab First-Line Maintenance for Advanced Urothelial Carcinoma: Long-Term Follow-up from the JAVELIN Bladder 100 Trial in Subgroups Defined by 1L Chemotherapy Regimen and Analysis of OS from Start of 1L Chemotherapy

(UroToday.com) Dr. Sridhar presents long-term follow-up from the JAVELIN Bladder 100 clinical trial in subgroups defined by first line (1L) chemotherapy regimen and an overall survival (OS) analysis from the start of 1L chemotherapy.

The JAVELIN Bladder 100 clinical trial¹ demonstrated a significant overall survival and progression-free survival benefit with avelumab 1LM + best supportive care (BSC) vs BSC alone for locally advanced or metastatic UC not progressing on platinum-based chemotherapy (PBC). As a result, avelumab was approved for 1L maintenance in various countries worldwide. With long-term follow-up (data cutoff 6/2021), median OS was 23.8 months vs. 15 months (HR 0.76) and median investigator assessed PFS was 5.5 vs. 2.1 months (HR 0.54).

The original study design and inclusion criteria are summarized below:

This post-hoc exploratory analysis assessed:

1. Outcomes from start of maintenance in subgroups defined by 1L chemotherapy regimen (cis/gem vs. carbo/gem) – but does not include patients who switched therapies
2. OS from start of 1L chemotherapy in the overall population and by 1L chemotherapy regimen

Table 1 (baseline characteristics by 1L chemotherapy regimen) and Table 2 (Patient disposition by 1L chemotherapy regimen) are found below:

Across both arms, patients who received carbo/gem were older, including a larger proportion of ECOG PS 1 or higher or creatinine clearance < 60 mL/min – consistent with cisplatin ineligibility criteria. In both subgroups, the most common reason to discontinue was disease progression.

In subgroups treated with 1L cisplatin + gemcitabine or carboplatin + gemcitabine, OS and PFS (measured from start of maintenance [randomization]) were longer in the avelumab + BSC arm than in the BSC alone arm (Table). In both subgroups, PFS was also longer with avelumab maintenance.

KM curves are demonstrated below:

In the overall population, median OS measured from the start of 1L chemotherapy was 29.7 months (95% CI, 25.2-34.0) in the avelumab + BSC arm and 20.5 months (95% CI, 19.0-23.5) in the BSC alone arm (HR, 0.77 [95% CI, 0.635-0.921]).

Safety findings were similar in both subgroups – with no new safety concerns identified (table below):

Presented by: Srikala S. Sridhar, MD, MSc, FRCPC, Princess Margaret Cancer Center, University Health Network

Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Associate Professor of Urology, University of California, Davis @tchandra_uromd on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.

References:

1. Powles T, Sridhar SS, Loriot Y, Bellmunt J, Mu XJ, Ching KA, Pu J, Sternberg CN, Petrylak DP, Tambaro R, Dourthe LM, Alvarez-Fernandez C, Aarts M, di Pietro A, Grivas P, Davis CB. Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial. Nat Med. 2021 Dec;27(12):2200-2211. doi: 10.1038/s41591-021-01579-0. Epub 2021 Dec 10. PMID: 34893775.