Atezolizumab met the primary endpoint of objective response in PD-L1â€“positive patients with advanced nonâ€“small cell lung cancer in the phase II BIRCH trial.
Sandra Horning, MD
Atezolizumab (MPDL3280A) met the primary endpoint of objective response in PD-L1—positive patients with advanced non–small cell lung cancer (NSCLC) in the phase II BIRCH trial, according to Roche, which manufactures the PD-L1 inhibitor. The results corroborate the phase II POPLAR data presented at ASCO 2015, in which atezolizumab improved survival versus chemotherapy in pretreated patients with PD-L1–positive NSCLC.
Based on early-stage studies, atezolizumab previously received a breakthrough therapy designation from the FDA as a potential treatment for patients with PD-L1—positive NSCLC following progression on prior therapy, including chemotherapy and targeted therapies. The BIRCH findings will contribute to ongoing discussions on atezolizumab between Roche and the FDA that were established under this designation.
“We plan to present results at an upcoming medical meeting and will discuss these data as well as results from our other lung cancer studies with health authorities to bring this medicine to patients as quickly as possible,’’ Sandra Horning, MD, chief medical officer and head of Global Product Development at Roche, said in a statement.
In the single-arm, open-label, multicenter phase II BIRCH trial, 667 patients with locally advanced or metastatic NSCLC received 1200 mg of IV atezolizumab every 3 weeks. All patients had disease that expressed PD-L1 as measured on tumor cells (TC) and tumor-infiltrating immune cells (IC) by Roche's investigational immunohistochemistry test (IHC). An IHC score of TC2/3 or IC2/3 was the inclusion criteria established by the trial design. Objective Response Rate (ORR) was the primary outcome measure with secondary measures including duration of response, overall survival (OS), progression-free survival (PFS), and safety.
Although results are not available yet, Horning commented, “We are encouraged by the number of people who responded to atezolizumab and maintained their response during the study, which is particularly meaningful for people who had received several prior treatments.”
Additionally, Roche noted that the safety profile for atezolizumab in the BIRCH trial was similar to previous adverse event outcomes reported for the PD-L1 inhibitor.
In the phase II POPLAR study presented at ASCO 2015, 287 patients with previously treated NSCLC were randomized to receive atezolizumab (n = 144) or docetaxel (n = 143). Intravenous atezolizumab was administered at 1200 mg every 3 weeks and docetaxel was used at 75 mg/m2 every 3 weeks. In the overall study population, the results did not significantly favor atezolizumab; however, as reported by Roche for the BIRCH trial, PD-L1 expression was strongly associated with atezolizumab's efficacy in POPLAR.
In patients with the highest level of PD-L1 expression (TC3/IC3), the median OS with atezolizumab was not yet reached compared with 11.1 months for docetaxel (HR, 0.46; 95% CI, 0.19-1.09). In this same group, the median PFS was 7.8 versus 3.9 months, for the anti—PD-L1 antibody and docetaxel, respectively (HR, 0.57). The ORR was 38% with immunotherapy and 13% with chemotherapy. In patients without PD-L1 expression (TC/IC 0), a difference was not observed between the two groups.
For patients with TC/IC 2 and 3 PD-L1 expression treated with atezolizumab (n = 50), the median OS was 13 months compared with 7.4 months for those treated with docetaxel (n = 55). Treatment with atezolizumab was associated with a 44% reduction in the risk of death for this group of patients (HR, 0.56; 95% CI, 0.33-0.95; P = .026). The median PFS was 4.0 versus 2.8 months (HR, 0.70; 95% CI, 0.45-1.08) and the ORR was 22% versus 18%, for atezolizumab and docetaxel, respectively.
In the study, fewer grade 3-5 adverse events were experienced by patients treated with atezolizumab compared with docetaxel (44% vs 56%). There was a higher incidence of respiratory side effects with immunotherapy versus chemotherapy. Atezolizumab was associated with aspartate and alanine aminotransferase increases (4% each), colitis (1%), hepatitis (1%), and pneumonitis (2%).
Beyond lung cancer, Roche is also examining atezolizumab in other tumor types, recently announcing that the phase II IMvigor 210 study of second-line treatment with atezolizumab in advanced urothelial bladder cancer met its primary ORR endpoint.
Overall, Roche has 11 ongoing or planned phase III trials involving atezolizumab in either lung, bladder, breast, or kidney cancer.