Avelumab continues to show promise for bladder cancer

In individuals with advanced urothelial carcinoma (UC), a first-line maintenance treatment regimen comprising a combination of avelumab and best supportive care (BSC) provided better survival benefit than BSC alone, according to long-term and subgroup analyses of the phase III JAVELIN Bladder 100 trial presented at ASCO GU 2022.

The study included 700 individuals (51 percent with PD-L1+ tumours) with unresectable locally advanced or metastatic UC without disease progression with 4–6 cycles of first-line gemcitabine plus carboplatin or cisplatin. Participants were randomized 1:1 to receive BSC either alone or in combination with avelumab.

Long-term follow-up

After a median follow up of ≥38 months, overall survival (OS) remained significantly longer with avelumab-BSC vs BSC alone, both in the overall cohort (23.8 vs 15.0 months; hazard ratio [HR], 0.76; p=0.0036) and among those with PD-L1+ tumours (30.9 vs 18.5 months; HR, 0.69; p=0.0064). An OS benefit was also seen with the combination regimen vs BSC alone across most subgroups* evaluated. [ASCO GU 2022, abstract 487]

A similar trend favouring avelumab-BSC vs BSC alone was also seen in terms of investigator-assessed progression-free survival (PFS; 5.5 vs 2.1 months; HR, 0.54; p<0.0001 [overall] and 7.5 vs 2.8 months; HR, 0.46; p<0.0001 [PD-L1+]).

Survival rates at 30 months were also longer with avelumab-BSC compared with BSC alone, both in the overall cohort (44 percent vs 34 percent [OS] and 19 percent vs 6 percent [PFS]) and in the PD-L1+ subgroup (51 percent vs 38 percent and 25 percent vs 7 percent, respectively).

After ≥12 months of treatment with avelumab-BSC, the most common any-grade treatment-emergent adverse events (TEAEs) were urinary tract infection and diarrhoea (13 percent for both). One patient died owing to a treatment-related AE (ie, immune-mediated nephritis). There were no new safety signals identified.

“[Our] long-term follow-up continued to show prolonged OS and PFS with avelumab-BSC vs BSC alone,” said Dr Thomas Powles from St Bartholomew’s Hospital, London, UK. This occurred despite more patients on BSC alone receiving subsequent anticancer drug therapy compared with those on avelumab-BSC (72 percent vs 53 percent), particularly PD-1/PD-L1 inhibitors (53 percent vs 11 percent), he added.

Asian subgroup

The avelumab-BSC combination remained better than BSC alone in the Asian** subpopulation (n=147), both in terms of OS (median 25.3 vs 18.7 months; HR, 0.74 [overall] and 26.1 vs 19.4 months; HR, 0.66 [PD-L1+]) and PFS (median 5.6 vs 1.9 months; HR, 0.58 and 6.8 vs 1.9 months; HR, 0.63, respectively). [ASCO GU 2022, abstract 486]

Objective response rates were higher with avelumab-BSC vs BSC alone (10 percent vs 3 percent [overall] and 12 percent vs 3 percent [PD-1+]), as were disease control rates (42 percent vs 26 percent and 50 percent vs 32 percent, respectively).

The most common grade ≥3 TEAEs with avelumab-BSC were anaemia (10 percent) followed by increased amylase levels (6 percent) and urinary tract infection (4 percent).

“The efficacy [and safety] of avelumab first-line maintenance in the Asian subgroup of JAVELIN Bladder 100 was similar to those reported in the overall trial population,” said Dr Masatoshi Eto from the Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.

Taken together, the current data further underpin the recommendation for avelumab first-line maintenance as SoC for individuals with advanced UC that has not progressed with 1L platinum-based chemotherapy (CT). [N Engl J Med 2020;383:1218-1230]