This phase III trial compares the effect of atezolizumab (or atezolizumab and recombinant human hyaluronidase) to standard observation for preventing cancer return after surgery (recurrence) in patients who have undergone a complete surgical removal (resection) of stage I non-small cell lung cancer (NSCLC). Patients who have undergone resection for lung cancer are typically followed by observation or active surveillance, which involves closely watching a patient's condition but not giving treatment unless there are changes in test results. During active surveillance, patients are given certain exams and tests done on a regular schedule. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Atezolizumab and recombinant human hyaluronidase is a formulation of atezolizumab combined with an enzyme called hyaluronidase, which helps increase tissue absorption of the drug. Giving atezolizumab or atezolizumab and recombinant human hyaluronidase after resection may be effective for preventing NSCLC recurrence, and may be a better approach to treating patients with stage I NSCLC than the usual observation approach.
Pathologically stage IA3 or IB NSCLC per American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 9th edition
Note: Tumors with any histology are allowed including both squamous and non-squamous subtypes, except those containing small-cell morphology. Non-squamous histology includes adenocarcinoma, large cell neuroendocrine, poorly differentiated tumors and adenosquamous, etc
Patient must have undergone complete surgical resection with negative margins (complete R0 resection). Surgical resection must be lobectomy or higher, unless the tumor measured no more than 2 cm based on clinical staging, where sub-lobar resection, e.g., wedge or segmentectomy, will be acceptable
Note: For patients who underwent sub-lobar resection for clinical tumors size of ≤ 2.0 cm, must have CT chest confirming tumor size within 60 days of surgical resection. Patients who received a lobectomy or higher do not require to fulfill this imaging criteria
None
Parallel
Atezolizumab
Biological/VaccineGiven IV
Atezolizumab and Recombinant Human Hyaluronidase
Biological/VaccineGiven SC
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood samples
Computed Tomography
Procedure/SurgeryUndergo CT
Patient Observation
Other interventionUndergo observation
Disease-free survival
Distributions of survival time between treatment arms will be compared with a one-sided stratified log-rank test. The rates at various timepoints and medians for each arm will be estimated using the Kaplan-Meier estimator. The 95% confidence interval will be calculated using Greenwood's formula and based on a log-log transformation applied to the survival function. Hazard ratios will be estimated using a stratified Cox regression model. Multivariable Cox models will be used to evaluate the treatment effect on survival time and its interaction with baseline covariates, including stage, systemic regimen, histology, and performance status.
Overall survival
Distributions of survival time between treatment arms will be compared with a one-sided stratified log-rank test. Will be estimated using the Kaplan-Meier estimator.
Lung cancer-specific survival
Will compare arms using a (stratified) cause-specific Cox model to estimate the cause-specific hazard ratio with a 95% confidence interval and Wald/score test. Will summarize absolute risk over time using cumulative incidence functions for lung-cancer death (with other-cause death as the competing risk). Will also estimate and compare the cumulative incidence of lung cancer death between arms and fit a Fine-Gray regression model (subdistribution hazard / cumulative incidence) to assess the subdistribution hazard ratio hazard ratio subdistribution (HRSD) (with 95% confidence interval), interpreting HRSD as the relative effect of treatment on the cumulative incidence of lung cancer death in the presence of competing non-lung-cancer mortality.
Recurrence-free survival
Recurrence will be characterized as loco-regional or distant. Distributions of survival time between treatment arms will be compared with a one-sided stratified log-rank test.
Rate of loco-regional recurrence
Will compare arms using stratified cause-specific Cox proportional hazards models to estimate cause-specific hazard ratios (with 95% confidence intervals and Wald/score tests), and will also fit Fine-Gray subdistribution hazards models to compare cumulative incidence in the presence of competing risks.
Disease free survival by sex
Estimates of disease-free survival and the corresponding 95% confidence intervals by sex will be provided.
Disease free survival by race
Estimates of disease-free survival and the corresponding 95% confidence intervals by race will be provided.
Disease free survival by ethnicity
Estimates of disease-free survival and the corresponding 95% confidence intervals by ethnicity will be provided.
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