The FDA has approved atezolizumab (Tecentriq, Genentech/Roche) for the treatment of patients with metastatic non–small-cell lung cancer (NSCLC) who have disease progression during or after platinum-containing chemotherapy and have progressed on an appropriate FDA-approved targeted therapy if their tumor has EGFR or ALK gene abnormalities.
The approval was based on results from the phase 3 OAK trial and from the phase 2 POPLAR trial. The larger study, OAK, showed that atezolizumab helped patients in the overall study population live a median of 13.8 months—4.2 months longer than those treated with docetaxel chemotherapy. The study enrolled subjects regardless of their programmed death ligand-1 (PD-L1) status and included both squamous and nonsquamous disease types.
The OAK trial was a global, open-label, randomized, controlled study that evaluated the efficacy and safety of atezolizumab compared with that of docetaxel in 1,225 patients with locally advanced or metastatic NSCLC whose disease had progressed after previous treatment with platinum-containing chemotherapy, with the primary analysis involving the first 850 randomized patients. Subjects with both squamous and nonsquamous disease were randomly assigned to receive either intravenous (IV) atezolizumab (1,200 mg every three weeks) or IV docetaxel (75 mg/m2 every three weeks). The coprimary endpoints were overall survival (OS) in all randomized patients (the intention-to-treat [ITT] population) and OS in a PD-L1–selected subgroup in the primary analysis population.
Median OS was 13.8 months for atezolizumab compared with 9.6 months for docetaxel in the primary analysis population (hazard ratio [HR], 0.74; P = 0.0004).
The POPLAR trial was a global, open-label, randomized study that evaluated the efficacy and safety of atezolizumab (n = 144) compared with that of docetaxel chemotherapy (n = 143) in patients with previously treated, recurrent, locally advanced or metastatic NSCLC. The study’s primary endpoint was OS; secondary endpoints included progression-free survival (PFS), the objective response rate (ORR), and safety.
Median OS was 12.6 months for atezolizumab and 9.7 months for docetaxel (HR, 0.69). The ORR was 15% in both groups. One patient (0.7%) in the atezolizumab group showed a complete response, and 15% of both groups showed a partial response. The median duration of response was 18.6 months for atezolizumab versus 7.2 months for docetaxel.
Possible serious adverse effects of treatment with atezolizumab include pneumonitis, hepatitis, colitis, hormone-gland problems (especially the pituitary, thyroid, and adrenal glands, and the pancreas), nervous system problems (neuropathy, meningitis, and encephalitis), eye inflammation, severe infections, and severe infusion reactions.
Atezolizumab is a monoclonal antibody designed to bind with the PD-L1 protein. Atezolizumab binds to PD-L1 expressed on tumor cells and on tumor-infiltrating immune cells, thereby blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the activation of T cells. Atezolizumab may also affect normal cells.
Source: Genentech; October 18, 2016.