Atezolizumab monotherapy demonstrated a statistically significant overall survival benefit in comparison with chemotherapy doublets in patients with untreated advanced non–small cell lung cancer with high PD-L1 expression and without <em>ALK </em>or <em>EGFR </em>mutations. This met the primary endpoint for the phase III IMpower110 trial, according to initial results release by Genentech, the developer of the PD-L1 inhibitor.
Sandra Horning, MD
Atezolizumab (Tecentriq) monotherapy demonstrated a statistically significant overall survival (OS) benefit in comparison with chemotherapy doublets in patients with untreated advanced nonsmall cell lung cancer (NSCLC) with high PD-L1 expression (TC3/IC3) and withoutALKorEGFRmutations. This met the primary endpoint for the phase III IMpower110 trial, according to initial results release by Genentech, the developer of the PD-L1 inhibitor.
Positive OS benefits were seen in both patients with nonsquamous and squamous NSCLC with atezolizumab compared with cisplatin or carboplatin and pemetrexed or gemcitabine chemotherapy. Additionally, the safety profile for single-agent atezolizumab was consistent with prior experiences of the agent and no new safety signals were reported.
“We are encouraged that Tecentriq monotherapy has shown a significant survival benefit over chemotherapy as an initial treatment in people with squamous or non-squamous non-small cell lung cancer with high PD-L1 expression,” Sandra Horning, MD, chief medical officer and head of global product development, Genentech, said in a press release. “These findings reinforce the potential of Tecentriq to play an important role in the treatment of multiple forms of lung cancer, and we look forward to discussing these data with health authorities.”
The company plans to submit data from the IMpower110 trial to both the FDA and the European Medicines Agency. Further findings from the study will also be presented at an upcoming medical meeting.
IMpower110 is a randomized, open-label phase III study that investigated the use of atezolizumab as a single agent compared with chemotherapy in patients with PD-L1selected, chemotherapy-naïve advanced nonsquamous or squamous NSCLC who areALKandEGFRwild type.
Eligible patients were required to have an ECOG performance status of 0 or 1, adequate hematologic and end-organ function, and tumor PD-L1 expression determined by immunohistochemistry. Those with known sensitizingEGFRorALKalterations, active or untreated central nervous system metastases, other malignancies in the past 5 years, a history of autoimmune disease, idiopathic pulmonary fibrosis or pneumonitis, HIV or active hepatitis B or C, or history of significant cardiovascular disease were excluded from the trial.
The trial enrolled 555 patients who were randomized 1:1 to receive either atezolizumab monotherapy or chemotherapy consisting of a platinum of cisplatin or carboplatin plus either pemetrexed for nonsquamous patients or gemcitabine for squamous patients. Patients in the chemotherapy control arm also received maintenance therapy of pemetrexed for nonsquamous disease or best supportive care for squamous disease.
Atezolizumab 1200 mg was administered intravenously every 21 days until disease progression, unacceptable toxicity, or death. The chemotherapy doublets were also given in 21-day cycles.
Patients were placed into subgroups by PD-L1 expression levels as determined by the SP142 assay test. The primary endpoint of the trial is OS by PD-L1 subgroup, and the key secondary endpoints are investigator-assessed progression-free survival, objective response rate, and duration of response.
Following positive OS signals meeting the primary endpoint, the trial will continue through its final analysis, which will include patients with lower PD-L1 expression levels.
Atezolizumab continues to be investigated as a single agent and in combination regimens in several phase III lung cancer trials.
Genentech’s Tecentriq (Atezolizumab) as a First-Line Monotherapy Helped Certain People With Advanced Non-Small Cell Lung Cancer Live Longer Compared With Chemotherapy [press release]. South San Francisco, CA: Genentech, a member of the Roche Group; September 12, 2019. https://bwnews.pr/2m9wxIE. Accessed September 12, 2019.