ESMO16: Atezolizumab significantly improves lung cancer survival vs standard chemotherapy in Phase III trial

A collaborative study recently presented at the ESMO Congress (held October 7–11; Copenhagen, Denmark) suggests that a novel PD-L1 inhibitor termed atezolizumab reduces the risk of death in patients with advanced non-small-cell lung cancer (NSCLC) following the failure of platinum-based chemotherapy, as demonstrated in the Phase III OAK trial.

Atezolizumab inhibits the binding of PD-L1 to its receptors, aiding in the restoration of tumor-specific T-cell immunity. The PD-L1 inhibitor has previously demonstrated potential survival benefit in patients in the Phase II POPLAR trial.

“The goal of this treatment is to allow the immune system to control and possibly eliminate cancer calls, so atezolizumab might be useful in a very large setting of different cancers,” commented investigator Fabrice Barlesi (Aix-Marseille University and the Assistance Publique Hôpitaux de Marseille, France).

The Phase III OAK study enrolled 1225 participants who had previously received treatment for NSCLC and randomized them into two groups – one receiving intravenous atezolizumab every 3 weeks and the other docetaxel every 3 weeks.

In the preliminary efficacy assessment of the initial 850 randomized patients, the researchers observed a 27% improvement in overall survival in the patients who received azetolizumab, compared with those who received docetaxel, regardless of their PD-L1 expression levels, including patients that displayed PD-L1 expression of less than 1%.

Additionally, the team discerned that when patients were arranged according to their level of PD-L1 expression, the overall survival was 59% greater among patients in the highest tertile of PD-L1 expression who were treated with azetolizumab, compared with the same group who received treatment with docetaxel.

However, the team also observed that participants who displayed no PD-L1 expression demonstrated a 25% improvement in overall survival with atezolizumab compared with those who received docetaxel. The improvements in overall survival were similar in patients with squamous and nonsquamous histology.

The findings of this study suggest that the use of anti-PD-L1 cancer immunotherapy could significantly improve survival in patients with metastatic NSCLC compared with chemotherapy, regardless of their PD-L1 expression level or their disease histology.

“This is the first Phase III study of atezolizumab, a PD-L1 inhibitor, and it confirms the efficacy seen in the POPLAR Phase II study, along with the results of PD-1 inhibitors,” elaborated Barlesi. “Azetizolumab offers a new second-line therapeutic strategy for patients with non-small-cell lung cancer, regardless of the PD-L1 status of the tumor.”

Commenting on the study, Martin Reck (Department of Thoracic Oncology at Lung Clinic Grosshansdorf, Germany) commented: “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.”

“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,” Reck explained. “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.”

Sources: Barlesi F, Park K, Ciardiello F et al. Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC. Presented at: 2016 ESMO Congress; October 7–11 (2016) Copenhagen, Denmark; ESMO press release