World Conference on Lung Cancer 2022: Updates in NSCLC - Episode 1

IMpower010 Trial Evaluating Atezolizumab Versus Best Supportive Care (BSC)

Dr Millie Das, MD opens a discussion surrounding updates regarding non-small cell lung cancer (NSCLC) as presented at the 2022 World Conference on Lung Cancer (WCLC).

Millie Das, MD: My name is Millie Das. I’m the chief of oncology at the Palo Alto VA [Veterans Affairs Medical Center] and a clinical associate professor at Stanford University.

The IMpower010 study involved patients with completely resected stages IB through IIIA non–small cell lung cancer. Patients with stage IB tumors had to have a tumor size greater than or equal to 4 cm. They had to have undergone resection with either a lobectomy or a pneumonectomy, and they had to have tumor tissue available for PD-L1 analysis. They went on to receive standard-of-care cisplatin-based adjuvant chemotherapy, and then were randomized 1:1 to receive atezolizumab given IV [intravenously] every 21 days for 16 cycles, which is the equivalent of a year, vs best-supported care. Patients were then followed for survival follow-up.

The primary end point was disease-free survival, which was tested hierarchically. First, they looked at the PD-L1 tumor proportion score of greater than or equal to 1% in the stage II and IIIA patient population. Next, they looked at disease-free survival in the all-randomized stage II to IIIA patient population. This included patients who didn’t have PD-L1 expression. Finally, they looked at disease-free survival in the intent-to-treat population, which included patients with stage IB disease as well.

The key secondary end points were overall survival in the intent-to-treat population, disease-free survival in the PD-L1 greater than or equal to 50% stage II to IIIA population, and then 3- and 5-year disease-free survival in all 3 populations. The interim overall survival data were presented at the World Conference on Lung Cancer. At ASCO [American Society of Clinical Oncology Annual Meeting] 2021, the disease-free survival in the PD-L1 greater than 1% patient population with stage II and IIIA disease was presented by my friend and colleague Dr Heather Wakelee. The stratified hazard ratio was 0.66 in favor of those receiving atezolizumab. This was the first phase 3 trial of adjuvant immunotherapy to report results. Based on the data presented at ASCO 2021, the FDA approved adjuvant atezolizumab in October 2021 for patients with PD-L1–positive resected stages II and IIIA non–small cell lung cancer.

The interim overall survival data that were presented support the disease-free survival data that led to FDA approval of atezolizumab for patients with PD-L1–positive stage II and IIIA disease. We saw a trend for overall survival benefit in favor of atezolizumab in this interim analysis. Unsurprisingly, the greatest benefit was seen in the PD-L1–high subgroup of patients. It’s important to remember that these subgroup analyses weren’t prespecified, so it’s somewhat difficult to make a general statement about the PD-L1 1%-to-49% subgroup of patients.

Given the disease disease-free survival benefit that has been seen in the patient cohort with a PD-L1 level of greater than or equal to 1%, this drug should still be offered to patients as we wait for additional years of data to be able to say with certainty whether there’s a survival benefit in this 1%-to-49% cohort. Disease-free survival is a clinically meaningful benefit that’s frequently assessed in adjuvant clinical trials. That was the primary end point of this study. The hope is always that we’ll see both a disease-free survival and overall survival benefit within intervention in the adjuvant setting. Though from the patient perspective, avoiding disease recurrence or progression is an important goal that can certainly impact quality of life, and other factors play into the shared decision-making of risks vs benefits in this setting.

Transcript edited for clarity.