Atezolizumab's Success in NSCLC Spells Further Trouble for Nivolumab

Roche has announced that phase 3 results from the OAK study evaluating atezolizumab (Tecentriq) indicate improved overall survival (OS) compared with docetaxel in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have progressed on platinum-based chemotherapy.

Announcing the results, Sandra Horning, MD, chief medical officer and head of Global Product Development at Roche, said in a press release: “These results add to the growing body of evidence that supports the role of Tecentriq as a potential new treatment for specific types of advanced NSCLC. This is very encouraging news for people living with this disease because lung cancer is the leading cause of cancer deaths around the world. We hope to bring this treatment option to patients as soon as possible.”

According to the release, atezolizumab, which inhibits the programmed death ligand-1 (PD-L1), improved OS independent of the patient’s PD-L1 status. Roche will now be presenting this data to the FDA to gain marketing access for atezolizumab, which had been granted priority review by the regulatory body in March this year, with an action date of October 19, 2016.

These results could mean additional trouble for Bristol-Myers Squibb (BMS)’s programmed death-1 (PD-1) inhibitor, nivolumab (Opdivo), whose phase 3 failure in treatment-naïve NSCLC patients stunned the industry. BMS was evaluating the efficacy of nivolumab, compared with investigator’s choice of chemotherapy, in untreated individuals diagnosed with NSCLC and expressing at least 5% of PD-L1.

Atezolizumab is designed to directly bind PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with PD-1 and B7.1 receptors, thereby activating T-cells, which in turn can attack tumor cells. The antibody has already been approved for the treatment of locally advanced or metastatic urothelial cancer that is resistant to platinum-based chemotherapy.

OAK is a phase 3 multi-center open-label randomized control trial designed to compare azetolizumab with docetaxel in patients with locally advanced or metastatic NSCLC whose disease is resistant to platinum-based agents. The primary end points of the trial included OS in the intention-to-treat population and PD-L1—expressing population. Secondary end points of the trial were objective response rate, progression-free survival, and objective response rate. The trial recruited 1225 patients and treatment continued until either physician-assessed clinical benefit or unacceptable toxicity was documented.

Roche, meanwhile, has 8 ongoing phase 3 studies in NSCLC that are evaluating azetolizumab in combination with other treatments in patients with early or advanced lung cancer.