In the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium 2023, Sridhar SS, et al. reported the post hoc analyses of the long-term outcomes of the phase 3 JAVELIN Bladder 100 trial, showing significantly longer overall survival (OS) with avelumab first-line (1L) maintenance + best supportive care (BSC) vs. BSC alone in patients with advanced urothelial carcinoma (aUC), regardless of the receipt of the 1L chemotherapy regimen.¹

The platinum-based combination chemotherapy is the current standard of care (SoC) in aUC.^2,3 However, most patients have disease progression within 9 months with a median OS of 14-15 months with cisplatin-based regimens and 9-10 months with carboplatin-based regimens if the patient is not eligible for cisplatin-based therapy.⁴ These patients require maintenance therapy to delay disease progression and prolong their OS.⁴ Since UC is characterized by high programmed death-ligand 1 (PD-L1) protein expression, the role of immunotherapy, in particular anti-programmed death-1 (PD-1) and anti-PD-L1 monoclonal antibodies, in aUC has increased in the recent years.⁴ Avelumab, an anti-PD-L1, has demonstrated superior efficacy in combination with BSC vs. BSC alone in the JAVELIN 100 trial and was approved for the maintenance treatment of locally aUC or metastatic UC (mUC) after disease progression,  during or after platinum-containing chemotherapy.⁴

In the JAVELIN 100 study, patients with unresectable, locally aUC/mUC who had no progression after 4-6 cycles of 1L cisplatin + gemcitabine or carboplatin + gemcitabine were eligible.¹ Patients (n=700) were randomized 1:1 to receive either avelumab 1L maintenance + BSC (n=350) or BSC alone (n=350), 4-10 weeks after completion of their 1L chemotherapy.¹ With a long-term follow-up of ≥38 months (data cutoff date: June 4, 2021), the median OS was 23.8 with avelumab + BSC vs. 15.0 months with BSC alone (HR=0.76; 95% CI=0.63-0.91; 2-sided p=0.0036); while the median investigator-assessed progression-free survival (PFS) was 5.5 months vs. 2.1 months (HR=0.54; 95% CI=0.46-0.64; p<0.0001).¹

An exploratory analysis of JAVELIN 100 for OS benefits from the start of randomization and 1L chemotherapy by the 1L chemotherapy regimen was conducted.¹ Compared with patients treated with cisplatin + gemcitabine (n=389), recipients of carboplatin + gemcitabine were generally older, having a poorer performance status, or creatinine clearance <60mL/min.¹ The observation was consistent with the standard criteria defining cisplatin ineligibility.¹ Results showed that avelumab + BSC achieved a significantly longer OS than BSC alone in both the cisplatin + gemcitabine (25.1 months vs. 17.5 months; HR=0.79; 95% CI=0.611-1.020) and carboplatin + gemcitabine (20.8 vs. 13.0 months; HR=0.69; 95% CI=0.516-0.925) subgroups from the start of randomization.¹ OS measured from the start of 1L chemotherapy was also longer with avelumab + BSC vs. BSC alone, irrespective of the 1L chemotherapy regimen received [cisplatin + gemcitabine: 31.0 months vs. 23.0 months (HR=0.79 95% CI: 0.613-1.024); carboplatin + gemcitabine: 25.8 months vs. 17.6 months (HR=0.69; 95% CI: 0.51-0.920).¹

The long-term safety profile, including adverse events (AEs) of any grade, serious or leading to interruption of avelumab, discontinuation or death, was similar in both the 1L chemotherapy subgroups, without new safety signals identified.¹

In conclusion, avelumab 1L maintenance demonstrated an improved OS among aUC patients, regardless of the receipt of initial 1L chemotherapy.¹ Avelumab 1L maintenance is now considered as the SoC in aUC patients who have no disease progression after their 1L platinum-based chemotherapy.⁵