First-Line Atezolizumab Plus Bevacizumab in Metastatic Nonsquamous NSCLC With High Tumor Mutation Burden

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In a Spanish phase II trial reported in JAMA Oncology, Mariano Provencio, MD, PhD, and colleagues found that the combination of atezolizumab and bevacizumab was active in the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) with high tumor mutation burden (TMB) and no EGFR, ALK, STK11, MDM2, or ROS1 alterations.

Mariano Provencio, MD, PhD

Mariano Provencio, MD, PhD

Study Details

In the multicenter trial, 38 evaluable patients enrolled between May 2019 and January 2021 received atezolizumab at 1,200 mg and bevacizumab at 15 mg/kg on day 1 of 21-day cycles, with treatment continued until disease progression or unacceptable toxicity. High TMB was defined as ≥ 10 mutations/megabase. The primary endpoint was 12-month progression-free survival, with a target rate of 40%.

Key Findings

Median follow-up was 22.1 months (interquartile range = 15.4–24.5 months). Progression-free survival at 12 months was 51.3% (95% confidence interval [CI] = 34.2%–66.0%), meeting the primary endpoint. Median progression-free survival was 13.0 months (95% CI = 7.9–18.0 months). The 18-month rate (92% data maturity) was 31.1% (95% CI = 16.9%–46.4%).

Median overall survival was not reached. Rates were 86.6% (95% CI = 70.8%–94.2%) at 6 months, 72.0% (95% CI = 54.1%–83.9%) at 12 months, and 62.3% (95% CI = 43.8%–76.2%) at 18 months.

Objective responses (all partial) were observed in 16 (42.1%) of 38 patients. Median duration of response was 11.7 months (range = 3.57–22.4 months), with 8 of 16 responses ongoing at the time of analysis. Stable disease was observed in an additional 14 patients (36.8%); the disease control rate was 78.9%. No association of PD-L1 expression with objective response, progression-free survival, or overall survival was observed.


  • Progression-free survival at 12 months was 51.3%, meeting the primary endpoint; the 18-month rate was 31.1%.
  • Median progression-free survival was 13.0 months.

Grade 3 or 4 adverse events considered related to atezolizumab occurred in five patients (13.2%), consisting of increased alanine aminotransferase, arthralgia, arthritis, diarrhea, and increased serum amylase in one patient each. Grade 3 or 4 adverse events considered related to bevacizumab occurred in six patients (15.8%), consisting of hypertension in two and increased alanine aminotransferase, anal fistula, myocardial infarction, and vascular disorder in one each. No treatment-related deaths occurred.

The investigators concluded, “These findings suggest that atezolizumab with bevacizumab is a potential treatment for high-TMB nonsquamous NSCLC.”

Dr. Provencio, of Hospital Puerta de Hierro-Majadahonda, Madrid, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by F. Hoffmann-La Roche, Spanish Lung Cancer Group, and others. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.