Atezolizumab Extends Disease-Free Survival in PD-L1–Positive Early-Stage NSCLC

Treatment with the immune checkpoint inhibitor atezolizumab (Tecentriq) following surgical resection and chemotherapy significantly improved disease-free survival (DFS) compared with best supportive care (BSC) alone in patients with stage II-IIIA non–small-cell lung cancer (NSCLC) and PD-L1 tumor composite score ≥1%, according to interim results from the phase 3 IMpower010 clinical trial, which were presented at the ASCO 2021 virtual annual meeting.

“The IMpower study is the first to show an immunotherapy is effective in early-stage NSCLC. This is an important advance, and potentially a step forward for many patients with lung cancer. For certain patients, atezolizumab can delay progression in advanced disease and perhaps even the need for more aggressive therapy,” said Julie R. Gralow, MD, FACP, FASCO, ASCO Chief Medical Officer and Executive Vice President, at a press conference held prior to the meeting.

“The advances in treating NSCLC have primarily been in the setting of advanced disease. This is the first phase 3 study to demonstrate that immunotherapy after surgery and chemotherapy can significantly delay recurrence in patients with early-stage lung cancer,” said lead investigator Heather Wakelee, MD, Chief, Division of Oncology, Stanford University Cancer Institute, Stanford University School of Medicine, CA.

The results from this trial underscore the importance of testing for biomarkers before the selection of therapy. “Given the significantly improved DFS with adjuvant atezolizumab in patients with PD-L1 expression, it is more important than ever to screen certain high-risk people for lung cancer early and detect PD-L1–positive tumors through biomarker testing. We now recommend testing patients with NSCLC for EGFR and PD-L1,” Dr Wakelee said. “In this trial, the vast majority of the benefit appeared to be in those patients whose tumors express PD-L1.”

Dr Wakelee explained that although there have been many advances in the treatment of patients with stage IV NSCLC over the past several years, the standard of care for early-stage disease has remained unchanged.

“The recent ADAURA trial found that adjuvant treatment with osimertinib [Tagrisso] improved outcomes for stages IB-IIIA EGFR-mutated NSCLC, but for the vast majority of these patients, the standard of care has not changed in over 15 years and remains 4 cycles of platinum-based chemotherapy,” she noted.

The use of adjuvant chemotherapy in completely resected NSCLC reduces the risk for recurrence by approximately 16%, she said. The IMpower010 trial was designed to determine whether atezolizumab added to chemotherapy would improve outcomes in patients with completely resected stage IB-IIIA NSCLC.

The IMpower010 Trial

The global phase 3 IMpower010 trial enrolled 1280 patients treated with adjuvant cisplatin-based chemotherapy after undergoing complete surgical resection for stage IB-IIIA NSCLC. Of these, 1005 patients were randomized in a 1:1 ratio to atezolizumab 1200 mg every 21 days or BSC.

The primary end point was DFS, which was analyzed for 3 subgroups: patients with stage II-IIIA NSCLC and PD-L1 tumor composite score ≥1%; all randomized patients with stage II-IIIA NSCLC; and an intent-to-treat analysis of patients with stage IB-IIIA NSCLC.

At a median follow-up of 32.8 months, atezolizumab reduced the risk for disease progression or death by 34% versus BSC in patients with stage II-IIIA resected NSCLC and PD-LI tumor composite score ≥1%. Median DFS was not reached in the atezolizumab group and was 35.3 months in the BSC group.

For all patients with stage II-IIIA NSCLC, the addition of atezolizumab reduced the risk for disease progression or death by 21% versus BSC. Median DFS in the atezolizumab and BSC groups was 42.3 months versus 35.3 months, respectively.

In the intent-to-treat analysis of all patients, including those with stage IB-IIIA NSCLC, the significance boundaries had not been crossed for DFS at the time of the interim analysis. The data have not yet been analyzed separately for stage IB patients, which comprised 12% of the study population. Survival data will be reported with longer follow-up.

“Obviously, we need FDA approval before atezolizumab is offered as standard of care. The FDA has approved osimertinib in earlier stage NSCLC and EGFR expression based on a DFS end point. The IMpower010 study showed that in patients with stage II-IIIA NSCLC and PD-L1 expression, atezolizumab after chemotherapy improved DFS and it is a more profound DFS benefit than we saw with chemotherapy. If approved, atezolizumab would be something I would want to offer my patients in that setting,” Dr Wakelee said.

Safety Profile

Adverse events (AEs) were consistent with the known safety profile of atezolizumab, and no new safety signals were observed during the trial. More patients who received atezolizumab after chemotherapy and surgery had any-grade AEs (92.7% vs 70.7% for BSC). Grade 3/4 AEs were reported in 21.8% and 11.5% of patients, respectively. Grade 5 treatment-related AEs occurred in 0.8% of the atezolizumab arm and were not applicable in the control arm. AEs leading to treatment withdrawal were reported in 18.2% of the atezolizumab arm and were not applicable in the control arm.

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