Final analysis data from ASTRES (EudraCT 2021-002695-40), a Phase 2 single-arm study, demonstrate that consolidation atezolizumab achieved a 12-month progression-free survival (PFS) rate of 54.9% in patients with unresectable, stage III non-small cell lung cancer (NSCLC) who had not progressed following platinum-based concurrent chemoradiation. With a median follow-up of 23.7 months (data cutoff: January 22, 2026), the results support an efficacy and safety profile consistent with established anti-PD-L1 monotherapy in this setting. The full findings will be presented at the 2026 World Conference on Lung Cancer in Seoul, South Korea.

Clinical Takeaway

In ASTRES, consolidation atezolizumab administered after platinum-based concurrent chemoradiation met its primary endpoint, achieving a 12-month IRF-assessed PFS rate of 54.9% (95% CI: 46.0%–63.7%) in patients with unresectable, stage III NSCLC. Median OS reached 38.8 months, with 67.5% of patients alive at 24 months. The safety profile was consistent with the known atezolizumab monotherapy profile, though grade 5 treatment-related AEs occurred in 3.1% of patients, including three pneumonitis-related and one pneumonia-related death.

Drug Profile & Mechanism

Atezolizumab is a humanized monoclonal antibody that targets programmed death-ligand 1 (PD-L1), blocking its interaction with both PD-1 and B7.1 receptors. This mechanism restores anti-tumor T-cell activity by preventing PD-L1-mediated immune suppression. In ASTRES, atezolizumab was administered intravenously at a fixed dose of 1680 mg every 4 weeks for up to 13 cycles, or until loss of clinical benefit or unacceptable toxicity.

Target Population

ASTRES enrolled patients with unresectable, stage III NSCLC who had not progressed after completing platinum-based concurrent chemoradiation. Key baseline characteristics of the 127 enrolled patients included:

  • Median age: 65 years (range: 29–81)
  • Sex: 80.3% male
  • Histology: 50.4% squamous
  • Disease stage: 15.7% with stage IIIC NSCLC
  • PD-L1 expression: 56.7% PD-L1-positive (tumor cell ≥1%)

Study Design

ASTRES (EudraCT 2021-002695-40) was a Phase 2, single-arm, open-label study evaluating consolidation atezolizumab in adults aged ≥18 years with unresectable, stage III NSCLC. Following completion of platinum-based concurrent chemoradiation without disease progression, eligible patients received intravenous atezolizumab 1680 mg every 4 weeks for up to 13 cycles, or until loss of clinical benefit or unacceptable toxicity. The final analysis was conducted with a data cutoff of January 22, 2026, at a median follow-up of 23.7 months.

Endpoints

  • Primary endpoint: Independent Review Facility (IRF)-assessed 12-month PFS rate
  • Secondary endpoints:
    • IRF-assessed median PFS and 24-month PFS rate
    • Objective response rate (ORR)
    • Duration of response (DOR)
    • Overall survival (OS), including 12- and 24-month OS rates
    • Safety

Efficacy Outcomes

Efficacy data were assessed in all 127 patients who received consolidation atezolizumab, with tumor response outcomes evaluated in a subset of 107 response-evaluable patients.

Progression-Free Survival

  • 12-month PFS rate (primary endpoint): 54.9% (95% CI: 46.0%–63.7%)
  • 24-month PFS rate: 40.8% (95% CI: 31.6%–50.0%)
  • Median IRF-assessed PFS: 16.7 months (95% CI: 10.5–22.1)

Overall Survival

  • Median OS: 38.8 months (95% CI: 28.6 months to not estimable)
  • 12-month OS rate: 79.3% (95% CI: 72.2%–86.4%)
  • 24-month OS rate: 67.5% (95% CI: 59.0%–76.0%)

Tumor Response (n=107 evaluable patients)

  • IRF-assessed ORR: 44.9% (95% CI: 35.8%–54.3%)
  • Median IRF-assessed DOR: Not estimable (95% CI: 23.2 months to not estimable), indicating durable responses among responding patients

Treatment Exposure

  • Median treatment duration: 11.0 months
  • 66.1% of patients received treatment for >6 months
  • Median dose intensity: 99.5%, indicating that most patients received atezolizumab close to the planned dose

Safety

Safety data were reported for all 127 patients who received atezolizumab.

Overall Adverse Events

  • Any-grade AEs: 95.3% of patients (n=121)
  • Grade 3/4 AEs: 24.4% of patients (n=31)
  • Grade 5 AEs: 9.4% of patients (n=12)

Treatment-Related Adverse Events (TRAEs)

  • Any-grade TRAEs: 76.4% of patients (n=97)
  • Grade 3/4 TRAEs: 11.0% of patients (n=14); most common (≥2%) included:
    • Pneumonia: 7.1%
    • Lymphocyte count decreased: 3.1%
    • Aspartate aminotransferase increased: 2.4%
  • Grade 5 TRAEs: 3.1% of patients (n=4), comprising 3 pneumonitis-related deaths and 1 pneumonia-related death

Treatment Withdrawal Due to AEs

  • AE-related treatment withdrawal: 5.5% of patients (n=7)
  • TRAE-related treatment withdrawal: 3.9% of patients (n=5)

Adverse Events of Special Interest (AESIs)

  • Any-grade AESIs: 58.3% of patients (n=74)
  • Grade 3/4 AESIs: 6.3% of patients (n=8)
  • Most common AESIs included:
    • Hepatitis (reported as laboratory abnormalities): any grade 22.8% (n=29); grade 3/4 2.4% (n=3)
    • Pneumonitis: any grade 20.5% (n=26); grade 3/4 0.8% (n=1)
    • Pancreatitis: any grade 3.9% (n=5); grade 3/4 2.4% (n=3)
    • Diabetes mellitus: any grade 2.4% (n=3); grade 3/4 1.6% (n=2)

Key Clinical Implications

✔ Consolidation atezolizumab achieved the primary endpoint, with a 12-month IRF-assessed PFS rate of 54.9% in patients with unresectable, stage III NSCLC following platinum-based concurrent chemoradiation.

✔ Median OS of 38.8 months and a 24-month OS rate of 67.5% suggest meaningful long-term survival benefit, though the single-arm design precludes direct comparison with other consolidation strategies.

✔ Responses were durable among the 44.9% of evaluable patients who responded; the median DOR was not estimable, with the lower bound of its 95% CI at 23.2 months.

✔ The safety profile was broadly consistent with known atezolizumab monotherapy; however, clinicians should be alert to the risk of pneumonitis, which contributed to three of the four grade 5 treatment-related deaths, and to the high frequency of hepatitis laboratory abnormalities (22.8% any grade).

✔ High dose intensity (median 99.5%) and treatment tolerability support the feasibility of this regimen, with only 3.9% of patients discontinuing due to treatment-related AEs.

✔ As a single-arm study, ASTRES does not establish comparative efficacy versus durvalumab or other consolidation approaches; these results should be interpreted within that methodological context.

Bottom Line

The final analysis of ASTRES demonstrates that consolidation atezolizumab is active and tolerable in patients with unresectable, stage III NSCLC after platinum-based concurrent chemoradiation, meeting its primary endpoint with a 12-month PFS rate of 54.9% and supporting durable responses and prolonged survival in this population. While the single-arm design limits comparative conclusions, these findings reinforce the potential role of anti-PD-L1 consolidation therapy in this setting and provide a comprehensive characterization of atezolizumab’s efficacy and safety profile for clinicians managing this patient population.

Sources:

  • ASTRES study investigators. ASTRES: A Phase 2, Single-Arm Study of Atezolizumab in Locally Advanced, Unresectable, Stage III, Non-Small Cell Lung Cancer (EudraCT 2021-002695-40). Final analysis data cutoff: January 22, 2026.