Ichiro Yoshino, MD, PhD, Professor and Chairman of the Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Japan, reviewed the finer details of the IMpower010 exploratory analysis.1 He maintained that atezolizumab’s benefit does, indeed, seem to favor some patient groups more than others.
Looking at the hazard ratios (HRs), he noted greater benefit among the 359 patients who had lobectomy (HR = 0.63; 95% confidence interval [CI] = 0.45–0.87), as compared with the 85 who underwent pneumonectomy (HR = 0.83; 95% CI = 0.43–1.58) in the PD-L1–expressing stage II–III population. This trend was mirrored in all randomly assigned patients with stage II–IIIA disease.
For the three-quarters of patients who underwent lobectomy in the study, Dr. Yoshino said: “The benefit of maintenance with atezolizumab was evident…. The type of surgery affected disease-free survival in IMpower010.”
Ichiro Yoshino, MD, PhD
Compared With Other Studies
Dr. Yoshino noted, in a quick look at other studies of patients with various non–small cell lung cancer (NSCLC) histologies, those that include a sizable proportion with squamous histology also tended toward greater utilization of pneumonectomy. Hence, the pneumonectomy rate appears to be aligned with squamous histology, he said. “The reason for the disadvantage in patients who had pneumonectomy in IMpower010 should be discussed.”
From this and other studies, it also appears that completion of four cycles of adjuvant chemotherapy is more likely for patients who do not receive cisplatin/vinorelbine and, in the current study, cisplatin/gemcitabine (HR = 1.14; 95% CI = 0.50–2.61). Among the regimens in IMpower010, the benefit was greatest with cisplatin/docetaxel (HR = 0.60; 95% CI = 0.30–1.23). Patients had to complete chemotherapy to proceed to maintenance atezolizumab; therefore, this information is important, Dr. Yoshino added.
More to Learn
Furthermore, Dr. Yoshino pointed out that certain cytotoxic drugs may be better partners for checkpoint inhibitors than others in terms of enhancing immunologic effects. Gemcitabine has previously been shown to have “relatively weak” immunostimulatory properties,2 he said. In IMpower010, cisplatin/gemcitabine also had the second lowest rate of compliance among the regimens and the worst disease-free survival. “Perhaps, the proper regimen is required for chemistry between chemotherapy and immunotherapy,” he suggested.
Taken altogether, these factors suggest there may be patients who benefit more than others from adjuvant immunotherapy: patients with tumors expressing PD-L1, those who undergo lobectomy (not pneumonectomy), and those who receive “proper” regimens of adjuvant chemotherapy—a point that warrants further examination, Dr. Yoshino concluded.
DISCLOSURE: Dr. Yoshino has served on speakers bureaus or advisory boards of AstraZeneca, Intuitive Surgical, Johnson & Johnson, Covidien, Daiichi Sankyo, and Chugai.
1. Altorki N, Felip E, Zhou C, et al: Impower010: Characterization of stage IB-IIIA NSCLC patients by type and extent of therapy prior to adjuvant atezolizumab. 2021 World Congress on Lung Cancer. Abstract PL02A.05. Presented September 9, 2021.
2. Galluzzi L, Humeau J, Buqué A, et al: Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat Rev Clin Oncol 17:725-741, 2020.
In an exploratory analysis of the pivotal phase III IMpower010 trial in stage II–IIIA non–small cell lung cancer (NSCLC), continued treatment with the monoclonal antibody atezolizumab after surgery and chemotherapy improved disease-free survival regardless of the type of surgery or chemotherapy...