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Maintenance therapy with a PD-L1 immune checkpoint inhibitor improved overall survival (OS) for patients with advanced bladder cancer and stable disease following first-line chemotherapy, an interim analysis of a phase III trial found.

Among 700 patients without disease progression on an initial platinum-based regimen, those randomized to maintenance avelumab (Bavencio) plus best supportive care had a median OS of 21.4 months, as compared with 14.3 months for those who received best supportive care alone (HR 0.69, 95% CI 0.56-0.86, P<0.001), reported Thomas Powles, MD, of the Barts Cancer Institute in London.

Progression-free survival (PFS) was also improved with the switch-maintenance strategy, at 3.7 months versus 2.0 months with chemotherapy alone (HR 0.62, 95% CI 0.52-0.75, P<0.001), according to findings from JAVELIN Bladder 100 presented at the virtual American Society of Clinical Oncology annual meeting, with presentations online this year due to the COVID-19 pandemic.

"Avelumab first-line maintenance in patients whose disease has not progressed with platinum-based induction therapy is a new first-line standard of care for advanced urothelial cancer," Powles said during a press briefing.

The study also met its co-primary endpoint, showing an OS improvement with avelumab in high PD-L1 expressors (HR 0.56, 95% CI 0.40-0.78). In patients with low PD-L1 expression, a trend toward improved OS was seen (HR 0.86, 95% CI 0.62-1.18).

"It's looking like it's going in the right direction," Powles told 乌鸦传媒. "From the patient's perspective, you'd clearly want to have the avelumab."

While 65%-75% of advanced bladder cancer patients respond to first-line platinum-based chemotherapy, these responses are typically brief. PD-1/L1-directed immunotherapy is already an approved first-line option, but only for patients who are ineligible for platinum-based chemotherapy. A number of these agents are approved in patients who progress on first-line chemotherapy, though in practice only about 25%-55% go on to receive second-line agents.

Reached for comment, Guru Sonpavde, MD, of the Dana-Farber Cancer Institute in Boston, called the trial "practice changing" for patients with stable disease following first-line chemotherapy.

"I would offer avelumab to all patients regardless of tumor PD-L1 status," said Sonpavde, who was not involved in the study. He noted that while the PD-L1-low subgroup appeared to benefit less, the analysis was not formally powered for such an analysis.

Other first-line trials are testing combinations of chemotherapy plus anti-PD-1/L1 immunotherapy upfront. One such trial -- IMvigor130 -- has already demonstrated a modest PFS improvement with atezolizumab (Tecentriq) added to platinum chemotherapy, but OS data remain immature and single-agent PD-1/L1 inhibition likely has a favorable therapeutic index, said Sonpavde.

"At this time, switch-maintenance avelumab for responding or stable patients on first-line platinum-based chemotherapy has set a high bar to beat," he said.

enrolled 700 patients with unresectable locally advanced or metastatic bladder cancer who achieved at least stable disease following first-line platinum-based chemotherapy. Following a treatment-free interval of 4 to 10 weeks, patients were randomized 1:1 to avelumab maintenance (10 mg/kg every 2 weeks) plus best supportive care (antibiotics, nutritional support, pain management, palliative radiotherapy) or best supportive care alone, until disease progression or unacceptable toxicity.

Patients were stratified by site of metastases (visceral vs non-visceral) and best response to chemotherapy (complete or partial response vs stable disease). Co-primary endpoints were OS in the overall population and PD-L1-positive subgroup, which made up 51% of the study cohort. Key secondary endpoints included PFS, objective response rates, safety and tolerability, and patient-reported outcomes.

Powles said that 62% of patients in the control arm went on to subsequent anti-cancer therapy, representing three-fourths of those with progressive disease. Safety was manageable, he reported, with toxicities in line with previous studies of avelumab monotherapy. All-grade toxicities occurred in 98.0% of patients in the maintenance arm compared with 77.7% in the control arm, and grade 3/4 events occurred in 47.4% and 25.2%, respectively.

While all subgroups appeared to benefit, significant OS improvements were seen regardless of induction chemotherapy (gemcitabine plus either cisplatin or carboplatin) or kidney function, and in patients who were older (≥65 years), had good performance status (ECOG 0), an objective response to chemotherapy, and non-visceral metastases.

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