Akihiko Gemma, MD

Department of Pulmonary Medicine and Oncology,
Graduate School of Medicine,
President, Nippon Medical School,
Tokyo, Japan

Atezolizumab demonstrated clinical tolerability in a large, real-world cohort of older patients with non-small cell lung cancer (NSCLC), according to results published in the Japanese Journal of Clinical Oncology.

“In the OAK study, atezolizumab significantly prolonged median overall survival (OS) by approximately 4.2 months compared with docetaxel in previously treated patients with metastatic NSCLC, and was better tolerated, with a lower overall incidence of adverse events,” the researchers wrote.

Akihiko Gemma, MD, and colleagues performed a prospective, observational, post-marketing surveillance study to examine the clinical tolerability and safety of atezolizumab in 2,570 patients with NSCLC (median age, 69; 69.9% male) that was deemed unresectable, progressive, or recurrent. Patients were treated with atezolizumab 1,200 mg every 3 weeks at 770 facilities between April 18, 2018 and March 31, 2020.

The researchers compiled data on patient characteristics, treatments, adverse events, and adverse drug reactions (ADRs), as well as information on severity, onset, and outcomes for ADRs. They followed patients for 12 months or until the discontinuation of atezolizumab.

Interstitial Lung Disease Most Frequent ADR

Dr. Gemma and colleagues reported ADRs in 29.1% of patients, most frequently pyrexia (4.2%). Grade 3 or higher ADRs were observed in 9.7% of patients younger than 75 and in 9.7% of those aged 75 or older. The incidence of grade 3 or higher ADRs was not impacted by the number of prior lines of therapy or the incidence or history of an autoimmune disorder, according to the study results.

Immune-related ADRs of interest that were observed in greater than 1% of patients included interstitial lung disease (ILD; 4.4%), endocrine disorders (4.3%), and hepatic dysfunction (2.8%). ILD occurred significantly more frequently in patients with a history of, or concurrent, ILD versus those without the disease (P≤0.001), and risk factors for the occurrence of grade 3 or higher ADRs included a history of, or concurrent, ILD. The researchers reported grade 5 ADRs in 35 patients, including 11 with concurrent ILD.

Atezolizumab was discontinued in 95/115 occurrences of ILD (82.6%), 15/19 occurrences of encephalitis/meningitis (78.9%), and 11/16 occurrences of severe skin disorders (68.8%),” the researchers wrote. “However, few infusion reactions (4/15; 26.7%) or endocrine disorders (15/119; 12.6%) led to atezolizumab discontinuation.”

The primary reasons for discontinuing atezolizumab included disease progression (N=1,684; 65.5%), adverse events (N=273; 10.6%), and cancer-related death (N=269; 10.5%).


Real-World Tolerability Comparable to Phase III Trial Data

Findings from the present study demonstrate that “the tolerability and safety of atezolizumab in a heterogeneous, real-world population of Japanese patients with NSCLC is comparable to the profile established in the randomized phase III clinical trials,” Dr. Gemma and colleagues wrote, calling the clinical tolerability of atezolizumab “excellent.”

“No new safety signals were identified and the risk and onset of immune-related [adverse events] were as expected,” the researchers continued.

They also noted that careful monitoring of patients with current and/or prior ILD is deemed necessary, “because the rate of fatal ILD was higher in these patients than in those without such a history.”