Early results from the IMpower010 trial showed an overall survival trend favoring adjuvant atezolizumab vs best supportive care for patients with PD-L1–positive (tumor expression ≥ 1%), stage II–IIIA (UICC/AJCC staging system, 7th ed), resected non–small cell lung cancer (NSCLC). These data were presented at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC).1 With a median follow-up of 45.3 months, however, this trend was not evident in the all-randomized stage II–IIIA or intent-to-treat population, which included patients with stage IB disease.
Findings from the first prespecified interim analysis of overall survival showed the highest magnitude of overall survival in patients whose tumor cells had PD-L1 expression of at least 50% and who received the PD-L1 inhibitor, authors of the study reported.
Enriqueta Felip, PhD
“This overall survival analysis shows a promising trend in favor of atezolizumab over best supportive care in the stage II–IIIA population with PD-L1 expression of at least 1% and a clinically meaningful improvement in the stage II–IIIA population with PD-L1 tumor expression of at least 50%, with overall survival improvements observed across most subgroups,” said Enriqueta Felip, PhD, Head of the Thoracic Cancer Unit, Oncology Department, at Vall d’Hebron University Hospital, Barcelona. “We will continue to follow patients in this study as data mature.”
For the IMpower010 trial, patients with stage II–IIIA NSCLC underwent complete surgical resection followed by adjuvant chemotherapy. Dr. Felip and colleagues then randomly assigned them to receive immunotherapy with atezolizumab or no further treatment.
A previous analysis of disease-free survival showed a significant benefit with adjuvant atezolizumab vs best supportive care in resected NSCLC following platinum-based chemotherapy. Based on these findings, atezolizumab was approved as adjuvant treatment after complete resection and platinum-based chemotherapy in patients with stage II–IIIA NSCLC and PD-L1 tumor expression ≥ 1% in several countries including the United States, China, and Japan. In the European Union, Canada, Switzerland, and the United Kingdom, atezolizumab was approved for stage II–IIIA NSCLC and PD-L1 tumor expression > 50% (with EGFR/ALK-positive disease excluded in the European Union).
Data presented during the 2022 WCLC evaluated overall survival and safety, with 13 months of additional follow-up to the previous interim analysis of disease-free survival.
Greatest Benefit in PD-L1–High Tumors
With a median follow-up of 46 months, the interim analysis demonstrated a trend toward improved overall survival among patients with PD-L1–positive (tumor expression of at least 1%), stage II–IIIA NSCLC (hazard ratio [HR] = 0.71). At 5 years, 76.8% of patients in the atezolizumab arm were alive compared with 67.5% of patients in the control arm. According to Dr. Felip, however, no separation in the curves was observed for the intent-to-treat population or the all-randomized, stage II–IIIA populations (HR = 0.95).
Among patients with PD-L1–positive, stage II–IIIA disease, a subgroup analysis of overall survival showed a trend toward improved survival in nearly all subgroups, regardless of tumor histology or stage. The importance of the PD-L1 biomarker was most pronounced in patients with PD-L1 expression of at least 50% (HR = 0.43). Patients with PD-L1 expression between 1% and 49% had a hazard ratio of 0.95, whereas those with PD-L1–negative tumors had a hazard ratio of 1.36.
“In patients with 50% or higher PD-L1 tumor expression, excluding [those with EGFR and ALK aberrations], median survival was not reached in either of the treatment arms,” Dr. Felip reported. “At 5 years, the overall survival rate was 84.8% for patients with stage II–IIIA disease and PD-L1 expression of at least 50% vs 67.5% in the control arm.”
Patients treated with adjuvant immunotherapy had an overall safety profile consistent with the previous analysis, and no new safety signals were observed. “These data support the previously reported positive benefit-risk profile of adjuvant atezolizumab,” Dr. Felip concluded.
DISCLOSURE: Dr. Felip reported financial relationships with Fundación Merck Salud, Grant for Oncology Innovation and Merck, Healthcare KGaA, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann–La Roche, GlaxoSmithKline, Janssen, Medscape, Merck KGaA, MSD, Novartis, Peptomyc, PeerVoice, Pfizer, Regeneron, Sanofi Genzyme, Seattle Genetics, Grifols, and Takeda.
1. Wakelee H, et al: IMpower010: Overall survival interim analysis of a phase III study of atezolizumab vs best supportive care in resected NSCLC. 2022 World Conference on Lung Cancer. Abstract PL03.09. Presented August 8, 2022.
Discussant of the IMpower010 abstract, Benjamin Besse, MD, PhD, Professor and Head of Clinical Research at Institute Gustave Roussy, Villejuif, France, said there is enough evidence to use adjuvant immunotherapy in stage II–IIIA resected non–small cell lung cancer (NSCLC), calling the increased...