Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC
Open accessAbstract
BACKGROUND: The cancer-cell-killing property of atezolizumab may be enhanced by the blockade of vascular endothelial growth factor-mediated immunosuppression with bevacizumab. This open-label, phase 3 study evaluated atezolizumab plus bevacizumab plus chemotherapy in patients with metastatic nonsquamous non-small-cell lung cancer (NSCLC) who had not previously received chemotherapy. METHODS: We randomly assigned patients to receive atezolizumab plus carboplatin plus paclitaxel (ACP), bevacizumab plus carboplatin plus paclitaxel (BCP), or atezolizumab plus BCP (ABCP) every 3 weeks for four or six cycles, followed by maintenance therapy with atezolizumab, bevacizumab, or both. The two primary end points were investigator-assessed progression-free survival both among patients in the intention-to-treat population who had a wild-type genotype (WT population; patients with EGFR or ALK genetic alterations were excluded) and among patients in the WT population who had high expression of an effector T-cell (Teff) gene signature in the tumor (Teff-high WT population) and overall survival in the WT population. The ABCP group was compared with the BCP group before the ACP group was compared with the BCP group. RESULTS: In the WT population, 356 patients were assigned to the ABCP group, and 336 to the BCP group. The median progression-free survival was longer in the ABCP group than in the BCP group (8.3 months vs. 6.8 months; hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.52 to 0.74; P<0.001); the corresponding values in the Teff-high WT population were 11.3 months and 6.8 months (hazard ratio, 0.51 [95% CI, 0.38 to 0.68]; P<0.001). Progression-free survival was also longer in the ABCP group than in the BCP group in the entire intention-to-treat population (including those with EGFR or ALK genetic alterations) and among patients with low or negative programmed death ligand 1 (PD-L1) expression, those with low Teff gene-signature expression, and those with liver metastases. Median overall survival among the patients in the WT population was longer in the ABCP group than in the BCP group (19.2 months vs. 14.7 months; hazard ratio for death, 0.78; 95% CI, 0.64 to 0.96; P=0.02). The safety profile of ABCP was consistent with previously reported safety risks of the individual medicines. CONCLUSIONS: The addition of atezolizumab to bevacizumab plus chemotherapy significantly improved progression-free survival and overall survival among patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression and EGFR or ALK genetic alteration status. (Funded by F. Hoffmann-La Roche/Genentech; IMpower150 ClinicalTrials.gov number, NCT02366143 .).
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Recent results from IMPOWER 150 indicate that atezolizumab, bevacizumab, and chemotherapy is effective in patients with NSCLC regardless of PD-L1 expression and EGFR or ALK genetic alteration status.
“Recent results from the IMPOWER 150 trial indicate that the combination of atezolizumab, bevacizumab, and chemotherapy is effective in patients with NSCLC, regardless of PD-L1 expression and EGFR or ALK genetic alteration status.”
From Afatinib for the treatment of <i>EGFR</i> mutation-positive NSCLC: A review of clinical findings (2020) · cites this paper as [109]
The Discussion states that adding atezolizumab to bevacizumab plus chemotherapy improved progression-free and overall survival regardless of PD-L1 expression or EGFR/ALK alteration status. The trial studied first-line treatment of metastatic nonsquamous NSCLC, however, so the citing sentence's unqualified reference to patients with NSCLC is broader than the evidence. (LLM, conf=0.86)
Experimental — accuracy not yet measuredChemotherapy plus immune checkpoint blockade has been recently approved as the first-line regimen for NSCLC, including patients with KRAS mutations.
“chemotherapy plus immune checkpoint blockade has been recently approved as the first-line regimen for NSCLC, including patients with KRAS mutations (45, 46).”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [46]
In the IMpower 150 trial, atezolizumab combined with carboplatin/paclitaxel/bevacizumab was associated with significant OS improvement (median OS N.R. vs 17.5 months, HR 0.54) compared with the same regimen without the anti-PDL1 agent.
“In the IMpower 150 trial, atezolizumab combined with carboplatin/paclitaxel/bevacizumab was associated with a significant improvement, in terms of OS (median OS N.R. vs. 17.5 months, HR 0.54), compared with the same regimen without the anti-PDL1 agent [108]”
Phase III data show overall survival and/or progression-free survival benefit for immune checkpoint therapy plus chemotherapy in non-small cell lung cancer, small cell lung cancer, triple-negative breast cancer, bladder cancer, and head and neck squamous cell carcinoma.
“Toward this end, combinations of ICTs with concurrent and/or sequential chemotherapy are under extensive investigation, with phase III clinical data demonstrating overall survival and/or progression-free survival benefi t in NSCLC ( 63-66 ), small cell lung cancer ( 51,52 ), triple-negative breast cancer ( 67 ), bladder cancer ( 53 ), and head and neck squamous cell carcinoma ( 68 ).”
From The Next Decade of Immune Checkpoint Therapy (2021) · cites this paper as [65]
Atezolizumab combined with chemotherapy is FDA-approved for squamous and nonsquamous NSCLC, small cell lung cancer, and PD-L1-positive triple-negative breast cancer.
“to date, atezolizumab, in combination with chemotherapy, has been approved by the FDA for the treatment of squamous and nonsquamous NSCLC, small cell lung cancer, and PD-L1-positive triple-negative breast cancer (66)(67)(68)(69).”
From Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance (2021) · cites this paper as [67]
Based on IMpower150, the FDA approved atezolizumab plus bevacizumab, paclitaxel, and carboplatin as the first-line treatment for advanced non-squamous NSCLC.
“Based on the results of IMpower150, the FDA approved atezolizumab plus bevacizumab, paclitaxel, and carboplatin as the first-line treatment for advanced non-squamous NSCLC [65].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [65]
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- Authors
- Socinski, M. A., Jotte, R. M., Cappuzzo, F., Orlandi, F., Stroyakovskiy, D., Nogami, N., Rodríguez-Abreu, D., Moro-Sibilot, D., Thomas, C. A., Barlesi, F., Finley, G., Kelsch, C., Lee, A., Coleman, S., Deng, Y., Shen, Y., Kowanetz, M., Lopez-Chavez, A., Sandler, A., & Reck, M.
- Affiliations
- Florida Hospital Cancer Institute (US)
- From the Florida Hospital Cancer Institute, Orlando (M.A.S.); Rocky Mountain Cancer Centers, Denver (R.M.J.); US Oncology, Houston (R.M.J.); Azienda Unità Sanitaria Locale della Romagna, Ravenna, Italy (F.C.); Instituto Nacional del Torax, Santiago, Chile (F.O.); Moscow City Oncology Hospital, Moscow (D.S.); National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan (N.N.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran...
- Allegheny Health Network (US)
- Genentech (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2018-06-14
- Volume
- 378
- Issue
- 24
- Pages
- 2288-2301
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2805354595
- Cited by
- 3,733
- References
- 5
- Citations by year
- 2026: 200 · 2025: 315 · 2024: 415 · 2023: 477 · 2022: 558 · 2021: 621 · 2020: 586 · 2019: 443 · 2018: 115 · 2017: 1
- FWCI
- 164.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Acceda (Universidad de Las Palmas de Gran Canaria) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- F. Hoffmann-La Roche Ltd/Genentech, Inc.
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- atezolizumab, bevacizumab, first-line therapy, immune checkpoint inhibitors, VEGF inhibition, carboplatin, paclitaxel, progression-free survival, overall survival, PD-L1 expression, maintenance therapy, liver metastasis
- MeSH terms
- Bevacizumab, Anaplastic Lymphoma Kinase, Aged, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Female, Humans, Immunotherapy, Lung Neoplasms, Male, Middle Aged, Mutation, Neoplasm Metastasis, Survival Analysis, Carboplatin, Paclitaxel, Genes, erbB-1, Receptor Protein-Tyrosine Kinases, Vascular Endothelial Growth Factor A, B7-H1 Antigen, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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