SUMMARY: Lung cancer is the second most common cancer in both men and women and the American Cancer Society estimates that for 2025, about 226,650 new cases of lung cancer will be diagnosed and 124,730 patients will die of the disease. Lung cancer is the leading cause of cancer-related mortality in the United States. Non-Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all lung cancers and Adenocarcinoma is now the most frequent histologic subtype of lung cancer. Of the three main subtypes of NSCLC, 30% are Squamous Cell Carcinomas (SCC), 40% are Adenocarcinomas and 10% are Large Cell Carcinomas. With changes in the cigarette composition and decline in tobacco consumption over the past several decades, Adenocarcinoma now is the most frequent histologic subtype of lung cancer.
Surgical resection is the primary treatment for approximately 30% of patients with NSCLC who present with early stage (I–IIIA) disease. These patients are often treated with platinum-based adjuvant chemotherapy to decrease the risk of recurrence. Nonetheless, 45-75% of these patients develop recurrent disease. There is therefore an unmet need for this patient population.
Atezolizumab (TECENTRIQ®) is an anti PD-L1 monoclonal antibody, designed to directly bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, thereby blocking its interactions with PD-1 and B7.1 receptors expressed on activated T cells. PD-L1 inhibition may prevent T-cell deactivation and further enable the activation of T cells.
IMpower 010 is a global, multicentre, open-label, randomized Phase III study evaluating the efficacy and safety of Atezolizumab compared with Best Supportive Care (BSC), in patients with stage IB-IIIA NSCLC, following surgical resection and up to 4 cycles of adjuvant Cisplatin-based chemotherapy. In this study, 1005 patients were randomized 1:1 to receive Atezolizumab 1200 mg IV every 3 weeks for 16 cycles, or BSC. Both study groups were well balanced and eligible patients had an ECOG PS of 0-1. The Primary endpoint was Disease Free Survival (DFS) in the PD-L1-positive (1% or more) stage II-IIIA patients, all randomized stage II-IIIA patients and Intent to Treat (ITT) stage IB-IIIA populations. Key Secondary endpoints included Overall Survival (OS) in the overall study population and ITT stage IB-IIIA NSCLC patients.
Initial DFS Results at a Median Follow-Up of 32.2 Months
Adjuvant Atezolizumab demonstrated a clinically meaningful DFS advantage:
- Stage II–IIIA, PD-L1 1% or more: 34% reduction in risk of recurrence or death vs. BSC (HR 0.66; P=0.0039); median DFS not reached vs. 35.3 months for BSC
- Stage II–IIIA, PD-L1 50% or more: 57% risk reduction (HR 0.43)
- All stage II–IIIA: HR 0.79 (P=0.02), median DFS gain of 7 months
- No statistically significant DFS improvement in the ITT population
- OS data immature at this stage
These findings led to regulatory approval of adjuvant Atezolizumab in resected stage II–IIIA PD-L1–positive NSCLC following chemotherapy.
Updated 5-Year Outcomes
Final DFS analysis and second OS interim analysis were reported with an additional 36 and 21 months of follow-up, respectively (clinical cutoff: January 26, 2024).
Disease-Free Survival:
- Stage II–IIIA, PD-L1 ≥1% (N=476): HR 0.70 (95% CI, 0.55–0.91) – More than 30-month median DFS difference between arms
- Stage II–IIIA, PD-L1 ≥50% (N=229): HR 0.48 (95% CI, 0.32–0.72)
- All stage II–IIIA (N=882): HR 0.83 (95% CI, 0.69–1.00)
- ITT (N=1005): HR 0.85 (95% CI, 0.71–1.01; P=0.07) – numerical improvement, not statistically significant
- All randomized Stage II–IIIA (N=882): HR 0.83 (95% CI, 0.69–1.00)
- PD-L1 ≥50% without EGFR/ALK alterations (N=209): HR 0.49 (95% CI, 0.32–0.75)
Overall Survival:
- ITT: HR 0.97 (95% CI, 0.78–1.22)
- Stage II–IIIA: HR 0.94 (95% CI, 0.75–1.19)
- PD-L1 ≥1%: HR 0.77 (95% CI, 0.56–1.06)
- PD-L1 ≥50%: HR 0.47 (95% CI, 0.28–0.77)
Since DFS in the ITT population did not cross the statistical significance boundary, formal OS testing was not conducted. OS data remain immature given a low event-to-patient ratio (~31%).
Clinical Perspective
IMpower010 remains the only Phase III trial with more than 5-year follow-up evaluating a checkpoint inhibitor as adjuvant therapy in resectable stage II–IIIA NSCLC. The most pronounced and durable benefits continue to be seen in PD-L1–selected populations, particularly those with PD-L1 50% or more and without EGFR/ALK alterations. These findings reinforce PD-L1 testing as a critical step in the adjuvant treatment algorithm for NSCLC, and they differentiate Atezolizumab from other checkpoint inhibitors evaluated in similar settings, where results have varied (e.g., KEYNOTE-091, BR.31)
Key Takeaways for Oncology Practice
- Patient selection matters – Benefit is greatest in PD-L1–positive, especially PD-L1 50% or more
- Durable effect – DFS benefit persists beyond 5 years in high PD-L1 subgroups
- Ongoing OS follow-up – OS data are still maturing; future analyses may clarify survival impact
- Safety reassurance – No new safety concerns after extended follow-up
Five-Year Survival Outcomes With Atezolizumab After Chemotherapy in Resected Stage IB-IIIA Non–Small Cell Lung Cancer (IMpower010): An Open-Label, Randomized, Phase III Trial. Felip E, Altorki N, Zhou C, et al. J Clin Oncol. 2025;43:2343-2349.
