Episode 1: IMpower010, first data on OS in first line treatment with azetolizumab in NSCLC patients
Presented by Prof Mariana Brandao (Institut Jules Bordet) and Prof Johan Vansteenkiste (University Hospitals Leuven)
In this first episode, Prof Mariana Brandao and Prof Johan Vansteenkiste engage in a discourse on the notable IMpower010 trial concerning adjuvant immunotherapy utilizing atezolizumab in patients with NSCLC.
Immunotherapy has profoundly transformed the management of metastatic and resectable lung cancer, with recent investigations conducted in the adjuvant, neo-adjuvant, and peri-operative settings. These trials uniformly employ either DFS or OS as (co)primary endpoints. It is noteworthy that approximately half of the patients achieve a cure through surgery alone. Consequently, the experts emphasize the careful consideration of the most significant endpoint. While PFS serves as a valuable parameter in clinical trials, the ultimate goal is OS. The significance of the IMpower010 trial lies in being the first adjuvant study to furnish OS data.
The initial interim analysis revealed a significantly improved HR for DFS in stage II-IIIA, particularly among patients with a high (>50%) PD-L1 expression, leading to EMEA registration for this patient subgroup. The presented interim data endorse the use of adjuvant atezolizumab for one year in patients with completely resected NSCLC and high (>50%) PD-L1 values. Unlike most recent trials excluding patients with EGFR/ALK alterations, the IMpower-010 study included such cases. Consequently, results were analyzed after excluding patients with EGFR mutations or ALK rearrangements, fortunately yielding similar outcomes to EGFR/ALK-negative patients. While the data are interim, they suggest alternative treatment avenues for these patients in the adjuvant setting.
The incorporation of atezolizumab not only extends treatment duration but also introduces additional toxicity to the already comprehensive treatment regimen of surgery and chemotherapy. Experts concur on the necessity to consider the toxicity profile, yet immunotherapy is generally well-tolerated, with manageable side effects. Particularly in patients with high (>50%) PD-L1 expression, where the treatment HR is 0.43, indicating a favourable risk/benefit ratio. As the utilization of atezolizumab transitions from metastatic to early setting, this consideration becomes crucial in guiding decision-making. Nonetheless, in practice, patients often opt for this supplementary treatment when it is proposed.
When contrasting these findings with the observation that pembrolizumab, as an adjuvant drug, confers benefits irrespective of PD-L1 status, the criteria guiding the choice between treatments for high (>50%) PD-L1 patients merit consideration. Disparities in treatment protocols between the two trials, where pembrolizumab is compared to placebo and atezolizumab is compared to best supportive care, including chemotherapy, could potentially explain differences in results. Currently, only atezolizumab has demonstrated an OS benefit. Given that OS should be the decisive parameter and atezolizumab is reimbursed in Belgium, experts concur that it should be the preferred choice while awaiting further results and follow-up data from the trials.
References:
Felip E et al. (2023) Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial. Annals of Oncology 34 (suppl_10): P907-919.