Roche presented positive results from three mid-stage trials at the European Cancer Congress (ECC) for its anti-PD-L1 antibodyatezolizumab, including data from the POPLAR and BIRCH studies in patients with advanced non-small-cell lung cancer (NSCLC), as well as the IMvigor 210 trial in patients with locally advanced or metastatic urothelial carcinoma (mUC). With regard to the lung cancer trials, Roche's chief medical officer Sandra Horning said the results "showed that measuring PD-L1 may help identify people most likely to respond to atezolizumab," adding that "we plan to submit these results to global health authorities to bring this potential new option to people as soon as possible." Meanwhile, the mUC results "may represent the first major treatment advancement in advanced bladder cancer in nearly 30 years," Horning remarked.
In the POPLAR study, 287 patients with previously treated locally advanced or metastatic NSCLC were randomised to receive either atezolizumab or docetaxel, both administered intravenously every three weeks. The primary endpoint was overall survival (OS), while secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. Results showed that, among patients whose tumours expressed medium and high levels of PD-L1, atezolizumab was associated with a significant survival benefit, with patients living 7.7 months longer than people who received docetaxel.
The previously announced BIRCH trial evaluated the safety and efficacy of atezolizumab in 667 patients with locally advanced or metastatic NSCLC whose disease expressed PD-L1. Participants were administered an intravenous dose of atezolizumab every three weeks. The main objective of the study was the ORR, while secondary endpoints included duration of response, OS, PFS and safety. Results demonstrated that atezolizumab met the primary endpoint, shrinking tumours in up to 27 percent of patients whose disease had progressed on previous treatment and also expressed the highest levels of PD-L1. Median survival had not yet been reached, the company said. Roche noted that in both studies of atezolizumab, adverse events were consistent with those observed in previous studies.
Barclay's analyst Michael Leuchten suggested Roche is under pressure to secure approval for atezolizumab. "Merck & Co. filed Keytruda (pembrolizumab) in lung cancer in April and Bristol-Myers Squibb has filed Opdivo (nivolumab)," he noted, adding that as a result "Roche needs to follow suit as soon as possible." For related analysis, see ViewPoints: Roche eyes second-line NSCLC filing for atezolizumab, but is the prize still on the table?
Meanwhile, the previously announced IMvigor 210 study tested atezolizumab in 311 patients with locally advanced or metastatic mUC, regardless of PD-L1 expression. The first cohort of the study, whose results are not yet mature, involved patients who received no prior therapies for their disease, but who were deemed unsuitable for first-line cisplatin-based therapy. Patients in this group received an intravenous dose of atezolizumab on the first day of 21-day cycles until progressive disease. The second cohort, whose results were presented at the ECC, included people whose disease had progressed during or following previous treatment with a platinum-based chemotherapy regimen. These patients received an intravenous dose of atezolizumab on the first day of 21-day cycles until loss of clinical benefit.
According to Roche, the IMvigor 210 findings demonstrated that atezolizumab shrank tumours in 27 percent of patients with mUC whose disease had medium and high levels of PD-L1 expression and worsened after initial treatment. Further, 92 percent of people who responded to atezolizumab continued to respond when the results were assessed. The company noted that median duration of response was not yet reached, while adverse events were consistent with those observed in previous studies.
Roche indicated that the data would be filed with global health authorities and to the FDA under atezolizumab's breakthrough therapy designation for the treatment of patients whose metastatic bladder cancer expresses PD-L1.
