The FDA ( Food and Drug Administration ) has approved Tecentriq ( Atezolizumab ) for the treatment of people with metastatic non-small cell lung cancer ( NSCLC ) who have disease progression during or following Platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumour has EGFR or ALK gene abnormalities.
This approval is based on results from the randomised phase III OAK and phase II POPLAR studies.
The largest study, OAK, showed that Atezolizumab helped people in the overall study population live a median of 13.8 months, 4.2 months longer than those treated with Docetaxel chemotherapy ( median overall survival: 13.8 vs. 9.6 months; HR = 0.74, 95% CI: 0.63, 0.87 ).
The study enrolled people regardless of their PD-L1 status and included both squamous and non-squamous disease types.
OAK is a global, multicentre, open-label, randomised, controlled study that evaluated the efficacy and safety of Atezolizumab compared with Docetaxel in 1,225 people with locally advanced or metastatic NSCLC whose disease had progressed following previous treatment with Platinum-containing chemotherapy, with the primary analysis consisting of the first 850 randomised patients.
Patients with both squamous and non-squamous disease were randomised ( 1:1 ) to receive either Atezolizumab administered intravenously at 1200 mg every 3 weeks or Docetaxel administered intravenously at 75 mg/m2 every 3 weeks.
The co-primary endpoints were overall survival in all randomised patients ( ITT population ) and in a PD-L1-selected subgroup in the primary analysis population.
POPLAR is a multicentre, open-label, randomised study evaluating the efficacy and safety of Atezolizumab compared with chemotherapy ( Docetaxel ) in people with previously treated recurrent locally advanced or metastatic NSCLC.
The primary endpoint was overall survival; secondary endpoints included progression-free survival, objective response rate ( ORR ) and safety.
The most common side effects ( greater than or equal to 20% ) in patients with metastatic non-small cell lung cancer were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation.
Nine patients ( 6.3% ) who were treated with Atezolizumab experienced either pulmonary embolism ( 2 ), pneumonia ( lung infection ) ( 2 ), pneumothorax, ulcer hemorrhage, cachexia secondary to dysphagia, myocardial infarction, or large intestinal perforation which led to death.
Atezolizumab was discontinued for adverse reactions in 4% ( 6 ) of the 142 patients.
Atezolizumab is a monoclonal antibody designed to target and bind to a protein called PD-L1 ( programmed death ligand-1 ), which is expressed on tumour cells and tumour-infiltrating immune cells. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this interaction, Atezolizumab may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells. ( Xagena )
Source: Roche, 2016