European Union Green Lights PD-L1 Companion Diagnostic for Adjuvant Atezolizumab in NSCLC

CE label expansion was granted to the Ventana PD-L1 (SP263) assay for use as a companion diagnostic to identify patients with non–small cell lung cancer (NSCLC) who are eligible for treatment with adjuvant atezolizumab (Tecentriq).¹

“With early detection of lung cancer, it is possible to give patients more treatment options and potentially improve a patient's outcome,” Jill German, head of Pathology Lab at Roche Diagnostics, said in a press release. “We are proud to offer a PD-L1 test that may qualify lung cancer patients for [atezolizumab] therapy. With this latest expansion, clinicians can consider multiple targeted immunotherapy options with one test to quickly determine the right treatment for each patient.”

On June 14, 2022, the European Commission approved atezolizumab for use as adjuvant therapy following complete resection and platinum-based chemotherapy in adult patients with NSCLC at high risk of recurrence whose tumors do not have EGFR mutations or ALK alterations but have a PD-L1 expression of 50% or higher.²

The approval was based on findings from an interim analysis of the phase 3 IMpower010 trial (NCT02486718), in which adjuvant atezolizumab led to a 57% reduction in the risk of disease recurrence or death vs 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).

The global, multicenter, open-label, phase 3 trial enrolled patients with completely resected, stage IB to IIIA NSCLC. Eligible patients had undergone lobectomy or pneumonectomy, had an ECOG performance status of 0 to 1, and had tumor tissue available for PD-L1 analysis.

A total of 1280 patients received 1 to 4 cycles of cisplatin plus pemetrexed, gemcitabine, docetaxel, or vinorelbine. Subsequently, 1005 of these patients were randomly assigned 1:1 to receive 1200 mg of atezolizumab every 21 days for 16 cycles or BSC.

The primary end point of the trial was investigator-assessed DFS, which 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 with stage IB to IIIA disease.

Secondary end points comprised OS in the ITT population, DFS in the group of patients with stage II to IIIA disease and a PD-L1 expression of 50% or higher, plus 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 at least 65 years of age. 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 a detected EGFR mutation or ALK alteration. Most patients underwent lobectomy, and the remainder underwent pneumonectomy.

Additional findings from the interim DFS analysis demonstrated that atezolizumab (n = 248) led to a significant improvement in DFS vs 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 The median DFS had not been reached (95% CI, 36.1–not evaluable [NE]) in the atezolizumab arm and was 35.3 months (95% CI, 29.0-NE) in the BSC arm.

Updated findings, which were presented during the 2022 European Lung Cancer Congress, showed that in patients with stage II to IIIA disease who had a PD-L1 expression between 1% and 49% (n = 247), the hazard ratio for DFS with atezolizumab vs BSC was 0.87 (95% CI, 0.60-1.26).⁴ 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 patients with a PD-L1 expression of 50% or higher whose tumors did not harbor EGFR or ALK alterations, the median DFS in the atezolizumab and BSC 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 safety profile of atezolizumab was consistent with what has previously reported with the agent, and no new safety signals were seen.

References

1. Roche's VENTANA PD-L1 (SP263) test gains CE label expansion as a companion diagnostic to identify non-small cell lung cancer patients eligible for Tecentriq. News release. Roche. August 24, 2022. Accessed August 24, 2022. https://prn.to/3KgJojc
2. European Commission approves Roche’s Tecentriq as adjuvant treatment for a subset of people with early-stage non-small cell lung cancer. News release. Roche. June 9, 2022. Accessed August 24, 2022. https://bit.ly/3xOWv6S
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. 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