The European Commission has approved atezolizumab for use as an adjuvant treatment following complete resection and platinum-based chemotherapy in adult patients with non–small cell lung cancer and a high risk of recurrence whose tumors do not have EGFR mutations or ALK alterations but have a PD-L1 expression of 50% or higher.
The European Commission has approved atezolizumab (Tecentriq) for use as an adjuvant treatment following complete resection and platinum-based chemotherapy in adult patients with non–small cell lung cancer (NSCLC) and a high risk of recurrence whose tumors do not have EGFR mutations or ALK alterations but have a PD-L1 expression of 50% or higher.1
The regulatory decision was supported by findings from an interim analysis of the phase 3 IMpower010 trial (NCT02486718), in which adjuvant atezolizumab was found to result in a 57% reduction in the risk of disease recurrence or death compared with best supportive care (BSC) in patients with stage II to IIIA NSCLC with PD-L1 expression of 50% or higher (n = 229; unstratified HR, 0.43; 95% CI, 0.26-0.71).
Notably, the disease-free survival (DFS) benefit derived with the immunotherapy over BSC was consistently observed across most of the subgroups analyzed on the trial, including histology and disease stage.
Although overall survival (OS) data remain immature for this population and this was not formally tested at the time of the DFS interim analysis, a trend toward improved survival with atezolizumab over BSC was observed (stratified HR, 0.39; 95% CI, 0.18-0.82).
“[This] approval represents an important advance, as [atezolizumab] becomes the first cancer immunotherapy approved in Europe for the treatment of certain types of early-stage NSCLC,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated in a press release. “Since approximately half of all people with early NSCLC develop recurrence after surgery, which in some cases is no longer curable, treating this cancer at an earlier stage offers the best chance to prevent recurrence.”
Patients with completely resected, stage IB to IIIA NSCLC were enrolled to the global, multicenter, open-label, phase 3 trial. To be eligible for enrollment, they were required to have undergone lobectomy or pneumonectomy, have an ECOG performance status of 0 to 1, and have tumor tissue available for PD-L1 analysis.
Study participants (n = 1280) received 1 to 4 cycles of cisplatin in combination with pemetrexed, gemcitabine, docetaxel, or vinorelbine. Subsequently, 1005 of these patients were randomized 1:1 to receive either atezolizumab at 1200 mg every 21 days for the duration of 16 cycles or BSC.
Patients were stratified based on gender (male vs female), stage of disease (IB vs II vs IIIA), histology, and PD-L1 expression (TC2/3 and any IC vs TC0/1 and IC2/3 vs TC0/1 and IC0/1).
Investigator-assessed DFS served as the primary end point of the trial; this was tested hierarchically in the patients with stage II to IIIA disease who had a PD-L1 expression of 1% or higher, the all-randomized population with stage II to IIIA disease, and the intention-to-treat (ITT) population who had stage IB to IIIA disease.
Secondary end points comprised OS in the ITT population and DFS in the group of patients with stage II to IIIA disease and a PD-L1 expression of 50% or higher, as well as 3- and 5-year DFS rates in all 3 patient populations.
Among the 1005 patients, the median age was 62 years (range, 26-84), and 38.0% of patients were 65 years of age or older. Additionally, 67% of patients were male, 73.5% were White, 55.5% had an ECOG performance status of 0, 78% were current or prior smokers, and 66% had nonsquamous histology.
Regarding disease stage, 12.5% of patients had stage IB disease, 47% had stage II disease, and 41% had stage IIIA disease. In terms of regional lymph node stage, 35% had stage N0, 35% had N1 disease, and 30% had N2 disease. Slightly more than half of patients did not have EGFR mutations or ALK alterations detected. Most patients underwent lobectomy, and the remainder underwent pneumonectomy.
At the time of the interim DFS analysis, atezolizumab (n = 248) was found to significantly improve DFS compared with BSC (n = 228) in the population of patients with a PD-L1 expression of 1% and stage II to IIIA disease (stratified, HR, 0.66; 95% CI, 0.50-0.88).3 In the investigative and control arms, respectively, the median DFS had not been reached (95% CI, 36.1–not evaluable [NE]) and 35.3 months (95% CI, 29.0-NE).
These data supported the October 2021 FDA approval of adjuvant atezolizumab in patients with stage II to IIIA NSCLC with a PD-L1 expression of 1% or higher, following resection and platinum-based chemotherapy.4 However, the greatest magnitude of benefit with this approach was observed in the population of patients with a PD-L1 expression of 50% or higher; due to this, the agent was approved for use in this indication in Switzerland, Canada, and the United Kingdom.
Findings presented during the 2022 European Lung Cancer Congress showed that in patients with stage II to IIIA disease who had a PD-L1 expression that ranged from 1% to 49% (n = 247), the hazard ratio for DFS with atezolizumab vs BSC was 0.87 (95% CI, 0.60-1.26).2 In the all-randomized population (n = 882), the HR for DFS was 0.79 (95% CI, 0.64-0.96). Additionally, in the ITT population (n = 1005), the HR for DFS was 0.81 (95% CI, 0.67-0.99).
Among those with a PD-L1 expression of 50% or higher whose tumors harbored EGFR or ALK alterations, the median DFS with the immunotherapy was not yet reached (95% CI, 42.3-NE) compared with 35.7 months (95% CI, 29.7-NE) with BSC (HR, 0.43; 95% CI, 0.27-0.68). In those without these alterations, the median DFS in the investigative and control arms was not yet reached (95% CI, NE-NE) and 37.3 months (95% CI, 30.1-NE), respectively (HR, 0.43; 95% CI, 0.26-0.71).
The toxicity profile of atezolizumab proved to be consistent with what has previously been observed with the agent. No new safety signals were observed.
Follow-up will continue and planned analyses of more mature OS data are expected to read out later this year.