Patel MR, et al. - This trial was designed in order to gauge the safety profile in patients (both post-platinum therapy and cisplatin-naive) treated with avelumab. Herein, the researchers also intended to discern the antitumour activity of this drug in post-platinum patients. Antitumour activity was illustrated by avelumab, in the treatment of patients with platinum-refractory metastatic urothelial carcinoma. This drug presented a manageable safety profile. Hence, evidence was yielded with regard to the therapeutic use of avelumab in metastatic urothelial carcinoma. Accelerated US FDA approval was yielded on this basis, in this scenario.

Methods

• This phase 1 dose-expansion JAVELIN Solid Tumor study recruited patients aged 18 years and older with histologically or cytologically confirmed locally advanced or metastatic urothelial carcinoma that had progressed after at least one previous platinum-based chemotherapy.
• The eligible candidates were enrolled from 80 cancer treatment centres or hospitals in the USA, Europe, and Asia.
• They presented with adequate end-organ function, an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, and at least one measurable lesion.
• The eligible participants also included cisplatin-ineligible patients who could have been previously treated in the perioperative setting, including platinum-naive patients.
• Enrollees unselected for PD-L1 expression received avelumab (10 mg/kg, 1 h intravenous infusion) every 2 weeks until confirmed disease progression, unacceptable toxicity, or other criterion for withdrawal.
• The primary endpoint included confirmed best overall response (according to RECIST version 1.1), adjudicated by independent review.
• In all patients who received at least one dose of avelumab, the safety analysis was carried out.
• A scrutiny was pursued of the antitumour activity in post-platinum patients who received at least one dose of avelumab.

Results

• A total of 329 patients with advanced metastatic urothelial carcinoma were analyzed for the enrolment process, between Sept 3, 2014, and March 15, 2016.
• This analysis identified 249 patients and they received treatment with avelumab for a median of 12 weeks (IQR 6.0-19.7) and followed up for a median of 9·9 months (4.3-12.1).
• Herein, researchers examined the safety and antitumour activity at data cutoff on June 9, 2016.
• In 161 post-platinum patients with at least 6 months of follow-up, a best overall response of complete or partial response was recorded in 27 patients (17%; 95% CI 11-24), with the inclusion of 9 (6%) complete responses and 18 (11%) partial responses.
• Infusion-related reaction (73 [29%]; all grade 1-2) and fatigue (40 [16%]) were determined to be the most frequent treatment-related adverse events (any grade in ≥10% patients).
• The occurrence of grade 3 or worse treatment-related adverse events was disclosed in 21 (8%) of 249 patients.
• Fatigue (four [2%]), and asthenia, elevated lipase, hypophosphataemia, and pneumonitis in two (1%) patients each were the common treatment-related adverse events.
• Among 249 patients, 19 (8%) reported a serious adverse event associated with the avelumab therapy, along with the occurrence of one treatment-related death (pneumonitis).