Adjuvant Atezolizumab Approaches EU Approval for High-Risk NSCLC With PD-L1 of ≥50%

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion supporting the approval of adjuvant atezolizumab (Tecentriq), after complete resection and platinum-based chemotherapy, in adult patients with non–small cell lung cancer (NSCLC) with a high risk of recurrence and whose tumors express PD-L1 of 50% or higher and do not harbor EGFR mutations or ALKalterations.¹

The recommendation was supported by findings from the phase 3 IMpower010 trial (NCT02486718), in which adjuvant atezolizumab resulted in a 57% reduction in the risk of disease recurrence or death vs best supportive care (BSC) in this patient population (unstratified hazard ratio [HR], 0.43; 95% CI, 0.26-0.71).² The benefit derived with the immunotherapy over BSC was consistently observed across most subsets, including histology or disease stage.

“The goal of treating early-stage cancers is to provide the best chance for a cure,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, stated in a press release. “Today’s announcement brings hope that, after a decade of limited treatment advances, many people in Europe with early NSCLC will soon have a new treatment option to reduce the risk of their disease returning.”

The global, multicenter, open-label IMpower010 trial enrolled patients with completely resected stage IB to IIIA NSCLC who have an ECOG performance status of 0 or 1, underwent lobectomy or pneumonectomy, and who had tumor tissue available for PD-L1 assessment.

A total of 1280 participants received 1 to 4 cycles of cisplatin plus pemetrexed, gemcitabine, docetaxel, or vinorelbine. A total of 1005 patients were then randomized 1:1 to receive atezolizumab at 1200 mg every 21 days for 16 cycles or BSC. Key stratification factors included gender (male vs female), disease stage (IB vs II vs IIIA), histology, and PD-L1 tumor expression status (TC2/3 and any IC vs TC0/1 and IC2/3 vs TC0/1 and IC0/1).

The primary end points of the trial were investigator-assessed DFS, which were tested hierarchically: PD-L1 expression of 1% or higher on tumor cells in the stage II to IIIA population, all-randomized patients with stage II to IIIA disease, and the intention-to-treat (ITT) population with stage IB to IIIA disease.

Secondary end points included overall survival (OS) in the ITT population, DFS in the subset of patients with PD-L1 expression of 50% or higher and stage II to IIIA disease, and 3- and 5-year DFS rates in all 3 populations.

In the 1005 patients, the median age was 62 years (range, 26-84), with 38.0% of patients aged 65 years or older. Moreover, 66.9% of patients were male, 73.4% were White, 77.9% were current or previous smokers, 55.3% had an ECOG performance status of 0, and 65.6% had nonsquamous histology. Regarding disease stage, 41.1% of patients had stage IIA disease, 29.4% had stage IIA disease, 17.3% had stage IIB disease, and 12.2% had stage IB disease. Additionally, 52.4% had tumors that did not harbor EGFR mutations and 57.1% had tumors that did not harbor ALK alterations. Approximately half, or 54.6%, of patients had PD-L1 tumor cell expression of 1% or higher.

At the time of the interim DFS analysis for the trial, atezolizumab (n = 248) significantly improved DFS over BSC (n = 228) in those with PD-L1 expression of 1% or higher on tumor cells and stage II to IIIA disease (stratified HR, 0.66; 95% CI, 0.50-0.88).³ The median DFS had not yet been reached (95% CI, 36.1–not evaluable [NE]) in the investigative arm vs 35.3 months (95% CI, 29.0-NE) in the control arm. These data supported the October 2021 FDA approval of adjuvant atezolizumab following resection and platinum-based chemotherapy in patients with stage II to IIIA NSCLC whose tumors have a PD-L1 expression of 1% or higher on tumor cells.⁴

However, the greatest magnitude of DFS benefit was observed in the subset of patients with PD-L1 expression of 50% or higher and stage II to IIIA disease (n = 229; unstratified HR, 0.43; 95% CI, 0.27-0.68). These findings led to the approval of the agent in this indication in Switzerland, Canada, and the United Kingdom.

Additional findings presented during the 2022 European Lung Cancer Congress indicated that the HR for DFS in the subset of patients with a PD-L1 expression ranging from 1% to 49% on tumor cells and stage II to IIIA disease (n = 247) was 0.87 (95% CI, 0.60-1.26). In the all-randomized population with stage II to IIIA disease (n = 882), the HR for DFS was 0.79 (95% CI, 0.64-0.96); it was 0.81 (95% CI, 0.67-0.99) in the ITT population (n = 1005).

In the subset of patients with a PD-L1 tumor cell expression of 50% or higher who had EGFR mutations or ALK alterations, the median DFS with adjuvant atezolizumab was not yet reached (95% CI, 42.3-NE) vs 35.7 months (95% CI, 29.7-NE) with BSC (HR, 0.43; 95% CI, 0.27-0.68). In those without those alterations, the median DFS had not yet been reached (95% CI, NE-NE) in the investigative arm vs 37.3 months (95% CI, 30.1-NE) in the control arm (HR, 0.43; 95% CI, 0.26-0.71).

OS data for those with high PD-L1 expression were still immature and not formally tested in the interim DFS analysis, but a trend toward an improvement in survival was noted with atezolizumab over BSC, with a HR of 0.36 (95% CI, 0.17-0.75). Follow-up will continue, and OS analyses are planned for later in 2022.

The safety profile observed with atezolizumab in patients with a PD-L1 tumor cell expression of 50% or higher proved to be consistent with that observed in the overall population of patients with stage IB to IIIA disease.

References

1. CHMP recommends EU approval of Roche’s Tecentriq as adjuvant treatment for a subset of people with early-stage non-small cell lung cancer. News release. F. Hoffman-La Roche Ltd. April 22, 2022. Accessed April 22, 2022. https://bit.ly/3OHl38e
2. Felip E, Altorki NK, Zhou C, et al. Atezolizumab (atezo) vs best supportive care (BSC) in stage II-IIIA NSCLC with high PD-L1 expression: sub-analysis from a pivotal phase III IMpower010 study. Ann Oncol. 2022;33(suppl 2):S71-S78. doi:10.1016/annonc/annonc857
3. Wakelee HA, Altorki NK, Zhou C, et al. IMpower010: primary results of a phase III global study of atezolizumab versus best supportive care after adjuvant chemotherapy in resected stage IB-IIIA non-small cell lung cancer (NSCLC). J Clin Oncol. 2021;39(suppl 15):8500. doi:10.1200/JCO.2021.39.15_suppl.8500
4. FDA approves atezolizumab as adjuvant treatment for non-small cell lung cancer. News release. FDA. October 15, 2021. Accessed April 22, 2022. https://bit.ly/3lHUgvQ