IMpower010: Adjuvant Atezolizumab Improved DFS in PD-L1 Expressing Stage II-IIIA NSCLC

IMpower010: Adjuvant Atezolizumab Improved DFS in PD-L1 Expressing Stage II-IIIA NSCLC

Meeting News
Jun 18, 2021
Leah Lawrence
Heather Wakelee

Adjuvant atezolizumab significantly improved disease-free survival (DFS) compared with best supportive care after chemotherapy in patients with resected stage II-IIIA NSCLC, according to the results of the IMpower010 study presented at 2021 ASCO Annual Meeting (Abstract 8500). 1

“IMpower010 is the first phase III study of cancer immunotherapy to demonstrate disease-free survival improvement in the adjuvant NSCLC setting,” said Heather A. Wakelee, MD, of Stanford University Medical Center, who presented the results. 

The addition of atezolizumab in patients with PD-L1 expressing tumors (≥ 1% using the tumor based SP263 assay) resulted in a 34% reduction in risk of death or disease recurrence (median not reached vs. 35.3 months; hazard ratio [HR]=0.66; 95% CI, 0.50-0.88; P = 0.0039). Atezolizumab also significantly improved DFS among all patients who were randomly assigned and who had stage II-IIIA disease, with a median DFS of 42.3 months compared with 35.3 months (HR = 0.79; 95% CI, 0.64-0.96; P = 0.0205).

“This indicates an enriched clinical benefit in patients whose tumors expressed PD-L1,” Dr. Wakelee, who is the Incoming President of the IASLC, said. “Atezolizumab may be considered a practice changing adjuvant treatment option for patients with resected PD-L1 expressing stage II-IIIA NSCLC.”

Abstract discussant Zosio Poitrowska, MD, MHS, of Massachusetts General Hospital, admitted that there has been some debate about whether DFS is a sufficient endpoint to change practice. 

“I would argue that as a clinician — and from the patient and caregiver perspective — disease-free survival is an important endpoint,” Dr. Poitrowska said. “It is hard to believe that this magnitude of improvement in disease-free survival would not translate into patient benefit even if overall survival (OS) is not improved.”

She echoed Dr. Wakelee’s conclusion that this improvement is clinically meaningful among patients with PD-L1 positive, stage II-IIIA disease. 

“Longer-follow-up, including overall-survival results as well as quality of life assessment will be required to more completely evaluate the value of adjuvant atezolizumab,” Dr. Poitrowska added. 

Trial Details

The IMpower010 trial enrolled 1,280 patients with completely resected stage IB-IIIA NSCLC. Of these, 1,269 received up to four 21-day cycles of cisplatin-based chemotherapy, and 1,005 were randomly assigned 1:1 to 16 cycles of atezolizumab or best supportive care. 

The primary endpoint was tested hierarchically. It was first evaluated in patients with stage II-IIIA disease with PD-L1 expressing tumors (≥ 1%). If the primary endpoint was met in that group, then the researchers looked at DFS in all patients with stage II-IIIA disease, then in the intent-to-treat (ITT) population. 

Dr. Wakelee reported results from a preplanned interim analysis with a median follow-up of 32.2 months in the ITT population. The median age of patients was 62; the majority of patients were male and Caucasian. Nonsquamous was the predominant histology.  PD-L1 expression of at least 1% was found in 54.6% of patients.

Although atezolizumab significantly improved DFS versus best supportive care in patients with stage II-IIIA disease, the significance boundary was not crossed for the ITT population (bringing in the 12% of patients on the trial with stage IB disease) at the interim analysis. The median DFS was not reached for atezolizumab compared with 37.2 months for best supportive care (HR = 0.81; 95% CI, 0.67-0.99; P = 0.0395). Testing will continue to the final DFS analysis in this population, Dr. Wakelee said. 

Effects for PD-L1 and ALK Involvement, Smoking Status

Among the patients who expressed PD-L1, all subpopulations seemed to benefit from atezolizumab with some exceptions, Dr. Wakelee said. Patients actively smoking at time of enrollment did not seem to have benefit, and patients with ALK rearrangement did not benefit with the addition of atezolizumab. 

Among all patients with stage II-IIIA who were randomly assigned, PD-L1 expression seemed to be quite important for a DFS benefit. Specifically, patients with greater than 50% expression had a hazard ratio of 0.43. However, when they looked at patients who did not have PD-L1 expression on their tumors, the hazard ratio was 0.97, indicating no DFS benefit with the addition of atezolizumab in that population. 

Dr. Wakelee said that OS data are immature. Because the significance boundary has not yet been crossed for DFS in the ITT population (still awaiting enough events), nor have there been enough OS events yet for results, it was not yet formally tested, Dr. Wakelee said.

The safety profile of atezolizumab was consistent with prior experience of atezolizumab monotherapy across indications and lines of therapy. 

Adverse Events

Among all-comers on this trial, adverse events of any grade occurred in 92.7% of patients assigned atezolizumab and 80.7% assigned best supportive care, which is not surprising in a group of patients who had recently completed surgery and chemotherapy. Grade 3/4 events occurred in 21.8% of patient assigned atezolizumab and 11% receiving best supportive care.  

Immune-related adverse events occurred more often in the atezolizumab arm, as expected. Immune-related adverse events were reported in 7.9% of patients receiving atezolizumab. There were 20 patients who had lab abnormalities for liver function tests that reached grade 3/4 , but less than 1% were thought to have true hepatitis, Dr. Wakelee said. 

Overall the results of Impower010 demonstrate a definitive DFS benefit with the addition of atezolizumab for patients with resected stage II-IIIA NSCLC after adjuvant chemotherapy, particularly in those patients whose tumors have PD-L1 expression of at least 1%.

 

References
  • 1. Wakelee HA, 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). Abstract 8500. Presented at: 2021 ASCO Annual Meeting.

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