The European Commission has granted regulatory approval to atezolizumab monotherapy for the treatment of patients with previously-treated locally advanced or metastatic non-small cell lung cancer and previously-treated locally advanced or metastatic urothelial carcinoma.
Sandra Horning, MD
The European Commission has granted regulatory approval to atezolizumab (Tecentriq) monotherapy for the treatment of patients with previously-treated locally advanced or metastatic non—small cell lung cancer (NSCLC) and previously-treated locally advanced or metastatic urothelial carcinoma (mUC).
The drug is indicated following chemotherapy for patients with NSCLC regardless of PD-L1 status. Patients with EGFR-activating mutations or ALK-positive tumor mutations should also undergo targeted therapy prior to starting on atezolizumab.
For patients with mUC, the monoclonal antibody is indicated following platinum-containing chemotherapy or for those who are considered ineligible for cisplatin chemotherapy, regardless of PD-L1 status.
The FDA previously approved atezolizumab for these indications.
“We are delighted that the European Commission has approved Tecentriq, the first anti—PD-L1 cancer immunotherapy approved in the EU, as a monotherapy in both advanced bladder and advanced lung cancer,” Sandra Horning, MD, chief medical officer and head of global product development for Roche, the developer of atezolizumab, said in a press release. “The totality of the data for Tecentriq across all indications including long-term responses in advanced bladder cancer and the overall survival advantage observed in our phase III advanced lung cancer study means that we are able to extend the benefits of Tecentriq to people living with these types of cancer regardless of their levels of PD-L1 expression.”
The NSCLC approval is based on results from the phase III OAK study and the phase II POPLAR study. Results from OAK showed that atezolizumab was associated with a 4.2 month-improvement in overall survival (OS) compared with docetaxel chemotherapy (13.8 vs 9.6 months; hazard ratio [HR], 0.73; 95% CI, 0.62-0.87).
The trial included 1225 patients with locally advanced or metastatic NSCLC—regardless of histology or PD-L1 status—who progressed during or after platinum-containing chemotherapy. Patients were randomly assigned to 75 mg/m2 of intravenous docetaxel (n = 425) or 1200 mg of intravenous atezolizumab every 3 weeks (n = 425).
Patient demographics were well balanced between the 2 arms at baseline. Median age was 64 years, 61% of patients were male, 18% had never smoked, and 25% had received 2 prior lines of therapy. Patients had an ECOG performance status of 0 (37%) or 1 (63%). Among patients randomized to docetaxel, 17% received immunotherapy as their next treatment.
The coprimary endpoints of the trial were OS in the entire study population and in a PD-L1—defined subgroup. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR). The primary efficacy assessment included only the initial 850 randomized patients.
PFS favored docetaxel (2.8 months vs 4 months; HR, 0.95). Investigator-assessed ORR was nearly identical between treatment groups (14% vs 13%) but atezolizumab showed clear superiority for DoR (16.3 months vs 6.2 months).
In POPLAR, a multicenter, international, randomized, open-label, controlled study; patients with previously treated NSCLC were randomly assigned to 3-week cycles of 1200 mg atezolizumab (n = 144) or 75 mg/m2 docetaxel (n = 143).
At a median follow-up of 22 months, an updated analysis following 200 deaths showed that atezolizumab was associated with a median OS of 12.6 months versus 9.7 months for docetaxel (HR, 0.69; 95% CI, 0.52-0.92). ORR (15.3% vs 14.7%) and median DoR (18.6 months vs 7.2 months) both favored the experimental group.
The approval for the mUC indication is based on results from the phase III IMvigor 211 trial and cohorts 1 and 2 from the phase II IMvigor 210. IMvigor 211 evaluated the efficacy and safety of atezolizumab compared with physician’s choice of chemotherapy (vinflunine, paclitaxel, or docetaxel) administered every 3 weeks in 931 patients who progressed during or following platinum-based treatment. The primary efficacy endpoint was OS and key secondary endpoints include ORR, progression-free survival, DOR, and safety.
The phase III trial failed to meet its primary endpoint for OS, but showed a median DoR of 21.7 months for atezolizumab compared with 7.4 months for chemotherapy.
In IMvigor 210, ORR was 63% for patients assigned to the experimental group compared with 21% for chemotherapy. Results from cohort 1 of IMvigor210 showed atezolizumab was associated with a median OS of 15.9 months in the overall study population.
Safety results included pooled data from 2160 patients with mUC or NSCLC. The most common adverse all-grade reactions were fatigue (35.4%), decreased appetite (25.5%), nausea (22.9%), dyspnea (21.8%), diarrhea (18.6%), pyrexia (18.3%), rash (18.6%), vomiting (15.0%), arthralgia (14.2%), asthenia (13.8%), and pruritus (11.3%).
Roche receives EU approval of TECENTRIQ® (atezolizumab) in a specific type of metastatic lung cancer and two types of metastatic bladder cancer. https://www.roche.com/media/store/releases/med-cor-2017-09-22c.htm. Accessed September 25, 2017.