According to results of the phase 3 IMpower010 trial presented at the 2021 ASCO Annual Meeting, immunotherapy with Tecentriq (atezolizumab), a PD-L1 inhibitor, after surgery and chemotherapy significantly improved the time of disease-free survival (no sign of cancer) compared with best supportive care in patients with early-stage (stage II-IIIA) non–small-cell lung cancer (NSCLC). The benefit was seen mainly in patients with NSCLC and PD-L1 expression on their tumor.
“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, ASCO Chief Medical Officer and Executive Vice President, who commented on the study results at the ASCO 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,” stated lead study investigator Heather A. Wakelee, MD, Division Chief of Medical Oncology and Deputy Director at Stanford Cancer Institute, California.
Both experts agreed that these results underscore the importance of testing for biomarkers before selecting therapy.
“Given the significantly improved disease-free survival 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.”
Although there have been a number of advances in the treatment of patients with stage IV (metastatic) NSCLC over the past few years, the standard of care for early-stage disease has been the same.
“The recent ADAURA trial found that adjuvant treatment with [Tagrisso] osimertinib improved outcomes for stages IA-IIIB 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,” Dr. Wakelee emphasized.
The use of adjuvant chemotherapy (additional therapy after primary treatment) in patients with NSCLC whose tumor was removed by surgery (complete resection), reduces the risk of disease recurrence (coming back) by about 16%, she said.
The IMpower010 study was designed to see if adding the checkpoint inhibitor atezolizumab to chemotherapy would improve outcomes in patients with completely resected early-stage (stage IA-IIIB) NSCLC.
The international phase 3 IMpower010 clinical trial enrolled 1,280 patients with stage IA-IIIB NSCLC who received adjuvant cisplatin-based chemotherapy after undergoing complete surgical resection of the tumor. Of these, 1,005 patients were divided into 2 groups to receive either atezolizumab every 21 days or best supportive care.
Disease-free survival was analyzed based on 3 subgroups: (1) patients with stage II-IIIB tumors and PD-L1 expression, (2) all patients with stage II-IIIA NSCLC, and (3) an intent-to-treat analysis of patients with stage IB-IIIA.
At an average follow-up of 32.8 months, in patients with stage II-IIIA and PD-LI expression, atezolizumab reduced the risk of disease progression or death by 34% versus best
supportive care. The average disease-free survival was not reached (meaning patients were still responding to treatment) in the atezolizumab group versus 35.3 months for those who received best supportive care.
For all patients with stage II-IIIA NSCLC, the use of atezolizumab after surgery reduced the risk of disease progression or death by 21% compared with best supportive care. The average disease-free survival was 42.3 months for the atezolizumab group versus 35.3 months with best supportive care.
The data have not yet been analyzed separately for the patients with stage IB NSCLC, who comprised 12% of the study population. Survival data will be reported with longer follow-up.
These data suggest that the benefit of atezolizumab after surgery is greater than that previously reported with chemotherapy in patients with early-stage NSCLC whose tumor was removed by surgery.
No new side effects emerged over the course of the study, and the safety of atezolizumab was similar to that reported previously with this immunotherapy.
Atezolizumab led to 92.7% side effects of any grade compared with 70.7% with best supportive care. Serious (grade 3-4) side effects were reported in 21.8% of patients who received atezolizumab versus 11.5% with best supportive care.
Side effects leading to treatment withdrawal were reported in 18.2% of the atezolizumab arm.
“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 disease-free survival end point,” Dr. Wakelee said. “The IMpower010 study showed that in patients with II-IIIA NSCLC and PD-L1 expression, atezolizumab after chemotherapy improved disease-free survival, and it has a more profound disease-free survival benefit than we saw with chemotherapy. If approved, atezolizumab would be something I would want to offer my patients in that setting.”