Atezolizumab Shows Lung Cancer Survival Improvement in Phase 3 Trial

Previously treated non-small cell lung cancer (NSCLC) patients who received atezolizumab saw significant improvement in survival compared with standard chemotherapy in a phase 3 study.

Atezolizumab is a PD-L1 inhibitor designed to use the body’s own immune system to fight cancer.

“The goal of this treatment is to allow the immune system to control and possibly eliminate cancer cells, so atezolizumab might be useful in a very large setting of different cancers,” said study investigator Fabrice Barlesi.

For the phase 3 OAK study, researchers enrolled 1225 patients with previously treated NSCLC. After participants were arranged according to PD-L1 status, histology, and number of prior chemotherapy regimens, they were randomized to receive 1200-mg intravenous atezolizumab every 3 weeks, or 75-mg/m2 docetaxel every 3 weeks.

A preliminary analysis was conducted of data from 850 patients. The results of the analysis showed that regardless of PD-L1 expression levels, there was a 27% improvement in overall survival in patients who received atezolizumab compared with patients in the docetaxel group (p=0.0003). This included patients with a PD-L1 expression of less than 1%.

When researchers examined the patients according to their level of PD-L1 expression, overall survival was 59% greater among patients who had the highest expression of PD-L1 and were treated with atezolizumab, compared with the same group treated with docetaxel.

“This is the first phase 3 study of atezolizumab, a PD-L1 inhibitor, and it confirms the efficacy seen in the POPLAR phase 2 study, along with the results of PD-1 inhibitors,” Barlesi said.

Researchers also saw that patients with no PD-L1 expression had a significant 25% improvement in overall survival with atezolizumab compared with docetaxel.

“Atezolizumab offers a new second-line therapeutic strategy for patients with non-small cell lung cancer, regardless of PD-L1 statues of the tumor,” Barlesi said.

The study authors noted that improvements in overall survival were found to be similar in patients with squamous and non-squamous histology.

“This is a very important piece of information on the role of PD-L1/PD-1 antibodies in treatment of non-small cell lung cancer, and confirms the overall survival benefits shown in the POPLAR and CHECKMATE trials,” said researcher Martin Reck. “Interestingly, the study also showed an improvement in overall survival, even in patients with no PD-L1 expression, which means we have a problem with using PD-L1 negativity as an exclusion factor for treatment.

“My suggestion would be that PD-L1 is perhaps one imperfect surrogate marker to describe the activity; it’s a good enrichment factor but we need additional markers for the characterization of patients who might not benefit from this treatment or who might really benefit.”