Patients with advanced or metastatic non-small cell lung cancer (NSCLC) whose disease progressed on platinum-based chemotherapy benefit more from the anti-PD-L1 immunotherapy Tecentriq (atezolizumab) than from standard Taxotere (docetaxel) chemotherapy, results of a Phase 3 study suggest.
The data, presented recently at the European Society for Medical Oncology (ESMO) 2016 Congress, showed that compared to standard chemotherapy, Tecentriq increased patients’ survival by nearly 30%.
“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,” Fabrice Barlesi, MD, head of theMultidisciplinary Oncology and Therapeutic Innovations Department at Aix-Marseille University and the Assistance Publique Hôpitaux de Marseille, France, said in a press release.
The randomized, open-label, multicenter, OAK Phase 3 study (NCT02008227) enrolled 1,225 patients with locally advanced or metastatic NSCLC who failed platinum-based chemotherapy. Participants were stratified according to their PD-L1 status, number of prior chemotherapy regimens, and histology, and then randomized to receive either intravenous Tecentriq (1200 mg every three weeks) or Toxotere (75 mg/m² every three weeks).
A preliminary analysis of data from 850 patients revealed that Tecentriq increased patients’ overall survival by 27% compared to Taxotere, irrespective of their PD-L1 status.
But when patients were analyzed according to their PD-L1 status, those with higher PD-L1 were the ones who showed greater benefit from Tecentriq treatment. Indeed, patients in the highest tercile of PD-L1 expression had a 59% increase in their overall survival compared to the same group treated with Taxotere.
This does not mean that those with lowest PD-L1 levels did not benefit from Tecentriq treatment over Taxotere. In fact, patients with no PD-L1 expression still had a significant 25 percent improvement in overall survival compared to the same group treated with Taxotere.
Histology, the researchers found, did not influence patients’ survival, as those with both squamous and non-squamous histology had similar overall survival rates.
“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,” said 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,” he said.
Martin Reck, PhD, professor in the Department of Thoracic Oncology at Lung Clinic Grosshansdorf, Germany, believes these findings suggest that using PD-L1 negativity may not be an accurate exclusion criteria for anti-PD-L1/PD-1 therapies.
“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,” Reck said.