At this year’s virtual annual European Society for Medical Oncology (ESMO) congress on 16–21 September, results were presented from the Phase III IMpower010 study for Roche and Genetech’s anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, Tecentriq (atezolizumab). Patients with completely resected, early-stage IB-IIIA non-small cell lung cancer (NSCLC), who had previously been treated with platinum-based chemotherapy, were randomised 1:1 to receive either Tecentriq or best supportive care (BSC). The primary endpoint was disease-free survival (DFS) in three patient populations, as assessed hierarchically by investigators.
Disease relapse occurs in up to 60% of patients with stage I–III NSCLC and is a high unmet need. Novel adjuvant therapies are, therefore, required in this setting. The IMpower010 study compares the efficacy of Tecentriq against that of BSC, which in this instance is observation and regular scans for disease recurrence. In order of hierarchical statistical testing, the three patient populations assessed are patients who have 1% or higher tumour cells that express the PD-L1 (stages II-IIIA), all randomised patients in stages II-IIIA, and the intention-to-treat (ITT) population (stages IB-IIIA). Analysis of previous interim DFS results of the study showed that DFS was statistically improved in patients after treatment with Tecentriq compared to those who received BSC. Follow-up analyses explored the sites of relapse and post-relapse treatment.
In the first patient population, there was a 34% reduction in the risk of disease recurrence or death with Tecentriq, with a hazard ratio of 0.66. Disease relapse was experienced in 45% of patients who received BSC versus only 29% of patients treated with Tecentriq. In addition, the median time to relapse with Tecentriq treatment was 17.6 months compared to BSC’s 10.9 months. Despite this, minimal differences in relapse times between the Tecentriq and BSC arms were observed in the other two patient populations, highlighting the prognostic value of PD-L1 expression. In a subgroup of patients with 50% or higher tumour cells expressing PD-L1, the hazard ratio was 0.43, the largest DFS improvement across all populations. There was no clear difference in patterns of the sites of relapses between arms, but post-relapse immunotherapy use was 35% in the BSC arm compared to Tecentriq’s 11%.
IMpower010 is the first randomised Phase III trial to show a significant DFS improvement after adjuvant cancer immunotherapy in early-stage NSCLC. These updated results confirm interim DFS analyses and could change the treatment paradigm in this setting. Roche aims to increase its NSCLC market share, which is currently dominated by Merck and Co’s Keytruda (pembrolizumab), by moving into this setting. GlobalData’s patient-based forecast expects Tecentriq to have the highest compound annual growth rate (CAGR) of the checkpoint inhibitors for NSCLC. Tecentriq’s sales in NSCLC in the eight major markets (8MM), namely the US, France, Germany, Spain, Italy, UK, Japan and China, are projected to reach $1.9bn by 2029 at a CAGR of 8.7%. DFS and overall survival analyses will continue in the ITT population, as well as obtaining long-term data to identify any differences between relapse patterns.