Exploratory biomarkers in JAVELIN Bladder 100: Avelumab 1L maintenance + BSC vs BSC alone for advanced UC

The JAVELIN Bladder 100 clinical trial (NCT02603432) has previously demonstrated that avelumab as a form of first-line (1L) maintenance and best supportive care (BSC) significantly prolonged overall survival (OS) versus BSC alone for advanced urothelial carcinoma (UC). Avelumab is an anti-PD-L1 immune checkpoint inhibitor (ICI) with a native IgG1 isotype backbone that can bind Fc receptors, stimulating the body’s immune system to find and kill cancer cells.

Now, the study has been further developed to report exploratory biomarker analyses. This is the first randomized Phase III trial that compares an ICI against BSC, and therefore provides a unique opportunity to analyze the predictive ability of several emerging biomarkers in advanced urothelial carcinoma (UC).1 Biomarker analysis allows for better characterization of disease and identification of novel therapeutic opportunities that could further improve outcomes with avelumab or other ICIs in patients with UC.

Exploratory endpoints included assessment of tumor biomarkers potentially related to antitumor immune activity and OS benefit with avelumab. Tumor tissue was collected from primary or metastatic lesions prior to 1L chemotherapy and was subjected to biomarker analysis by either IHC or next-generation sequencing. Ad hoc exploratory analyses of associations between tumor biomarkers and OS were conducted.

Results demonstrated that OS benefits of avelumab 1L maintenance in patients with advanced UC are positively associated with biomarkers of immune activity, such as CD8+ T cells in the invasive margin or tumor center, and negatively associated with biomarkers of tumor homeostasis and chronic inflammation, such as tumor epithelial cell gene signatures.

OS and PFS benefit with avelumab 1L maintenance observed across prespecified subgroups in JAVELIN Bladder 100

Results from the Phase III JAVELIN Bladder 100 trial (NCT02603432), demonstrated that avelumab, an anti-PD-L1, used as first-line (1L) maintenance along with best supportive care (BSC) significantly prolonged overall survival (OS), when compared to BSC alone, in patients with advanced urothelial carcinoma (UC) without disease progression with 1L induction chemotherapy (CTx) (gemcitabine + cisplatin [GemCis] or carboplatin [GemCar]) in all randomized patients and patients with PD-L1+ tumors. Further investigation was carried out focusing on OS benefit with avelumab + BSV versus BSC alone, analysis was carried out in prespecified subgroup.2

 

The OS and PFS benefit with avelumab 1L maintenance occurred irrespective of 1L CTx regimen patients had received. For patients receiving GemCis (n = 389), median OS (95% CI) was 25.3 months (18.6-NE) compared to 16.5 months (13.4-26.8) for avelumab + BSC versus BSC alone, respectively. Median progression-free survival (PFS) (95% CI) was 4.6 months (3.6-6.8) for avelumab + BSC, compared to 2.0 months (1.9-3.6) for BSC alone. Hazard ratios (HR) were 0.69 (95% CI, 0.51-0.94) and 0.63 (95% CI, 0.50-0.81) for OS and PFS, respectively. Patients that had received GemCar saw a similar trend, with a HR of 0.66 (95% CI, 0.47-0.91) for OS and 0.59 (95% CI, 0.44-0.80).

When assessing best response in subgroups of patients with complete response (n = 179), partial response (n = 326) and stable disease (n = 195), OS and PFS benefit with avelumab 1L maintenance was observed irrespective of best response to 1L chemotherapy. Furthermore, OS benefit with avelumab 1L maintenance was observed across additional prespecified subgroups, with no significant treatment-by-subgroup interaction observed for any subgroup variable (at 0.05 level).

To conclude, these results support the approval of avelumab 1L maintenance and its inclusion in the European Society of Medical Oncology (ESMO) guidelines as a new standard of care for 1L treatment of advanced UC.

References

  1. Sridhar S, et al. Avelumab first-line (1L) maintenance + best supportive care (BSC) vs BSC alone for advanced urothelial carcinoma (UC): Association between clinical outcomes and exploratory biomarkers. Annals of Oncology. 2020;31(suppl 4):S550-S550.
  2. Grivas P, et al. Avelumab first-line (1L) maintenance + best supportive care (BSC) vs BSC alone with 1L chemotherapy (CTx) for advanced urothelial carcinoma (UC): Subgroup analyses from JAVELIN Bladder 100. Annals of Oncology. 2020;31(suppl 4):S550-S550.

Written by Frankie Lewns

Sign-up for our Newsletter!

Keep up to date with all the latest news with our monthly newsletter