Atezolizumab Combo Demonstrates Favorable Efficacy and Safety Data for NSCLC with Untreated Brain Metastases

Patients with non-small cell lung cancer with brain metastases experienced a favorable safety profile along with efficacy results when treated with atezolizumab plus chemotherapy.

Patients with advanced non-squamous non-small cell lung cancer (NSCLC) with untreated brain metastases had favorable safety and efficacy results when treated with the combination of atezolizumab (Tecentriq) plus carboplatin and pemetrexed, according to data from the phase 2 ATEZO-BRAIN trial (NCT03526900) presented at the 2021 World Conference on Lung Cancer.

At a median follow-up of 17.3 months, the combination elicited a median systemic progression-free survival (PFS) of 8.9 months (95% CI, 6.7-13.8) in the 40-patient population. The median intracranial PFS was 6.9 months (95% CI, 4.7-12.1). The 18-month PFS rate was 24.9% and 10.4% systemically and intracranially, respectively.

“Brain metastases are the most frequent cancer-related neurological complication and are associated with a negative impact in quality of life and neurocognitive function, as well as being associated with poor prognosis,” explained Ernest Nadal, MD, a medical oncologist at the Catalan Institute of Oncology and an assistant professor at the Universitat de Barcelona in L'Hospitalet de Llobregat, Spain. “Patients with untreated brain metastases and those who have received corticosteroids have been excluded or underrepresented in many [previous] trials evaluating chemotherapy plus immunotherapy in the first-line setting. We have data from previous studies demonstrating that immunotherapy and chemotherapy could yield promising intracranial efficacy and safety results in NSCLC.”

Eligible patients had untreated stage IV non-squamous NSCLC with untreated brain metastases and were EGFR/ALK negative, regardless of PD-L1 expression. To be included in the study, patients also needed to register an ECOG performance status of 0 to 1 and have measurable lesions systemically and in the brain. Anticonvulsivants and dexamethasone ≤4 mg daily was allowed.

The primary end points of the study were safety and investigator-based PFS by RECIST v1.1 in and RANO-BM. Secondary end points included overall response rate (ORR), overall survival (OS), quality of life, and time to brain radiotherapy. The exploratory end point was to identify neuroimaging and blood biomarkers that could potentially predict response or resistance.

Atezolizumab, a monoclonal antibody, was administered intravenously at a dose of 1200 mg once every 3 weeks for 4 to 6 cycles. Carboplatin (5 AUCs) and pemetrexed (500 mg/m2) were given over the same dosing schedule. Afterwards, pemetrexed 500 mg/m2 and atezolizumab 1200 mg were administered once every 3 weeks for maintenance until tumor progression or unacceptable toxicity for a maximum of 2 years. Tumor evaluation was performed via body CT scan and brain MRI every 6-weeks until week 12, then every 9-weeks until disease progression.

The study, conducted at 11 cancer centers across Spain, utilized a Multc Lean Bayesian statistical design to monitor safety and efficacy. Investigators determined that a sample size of 40 patients was necessary, assuming a PFS rate of 50% at 12 weeks and a maximum grade 3/4 toxicity of 35%. Safety and efficacy were assessed every 5 patients.

The median age of the study population was 62.6 (IQR 11.5) and 72.5% of patients were male. All patients were Caucasian, 75% were smokers or former smokers and 15% never smoked. Most participants were patients with lung adenocarcinoma histology (97.5%) and an ECOG performance status of 1 (65%).

Investigators concluded the 12-week PFS rate was 60%, exceeding the expected rate of 50%. The grade 3/4 toxicity rate was 27.5%, falling into the acceptable range of 0%-35%. Median OS was 13.6 months (95% CI, 9.7-not reached) and the 2-year OS rate was 32%

The intracranial ORR per RANO-BM was 40%. Four (10%) patients achieved a complete response and 47.5% experienced stable disease (SD). The systemic ORR, made up of all partial responses (PRs), was 47.5% according RECIST v1.1 and 40% of patients had SD. Only 4 patients had discordance among systemic and central nervous system response, 2 with disease progression in the body and SD in the brain and 2 with disease progression in the brain and a PR in the body.

In terms of safety, most treatment-related adverse events (TRAEs) were grade 1/2. Investigators observed grade 4 thrombocytopenia, neutropenia, and hallucinations in 1 patient each. No fatal TRAEs occurred.

Common AEs of any grade included fatigue (60%), anemia (45%), dyspnea (28%), and nausea (28%). Grade 3 AEs included anemia (20%), back pain (10%), thrombocytopenia (5%), and dyspnea (3%). Immune-related AEs of any grade mostly consisted of skin rash (20%), anorexia (20%), alanine transaminase increase (13%), and aspartate transaminase increase (13%). Two patients had grade 3 immune-related AEs, 1 with increased ALT and 1 with pneumonitis.

“The safety profile and efficacy of atezolizumab with chemotherapy was favorable in patients with NSCLC with untreated brain metastases, including those receiving corticosteroids. Most responses were concordant in the body and brain,” concluded Nadal. “Currently, we are conducting correlative studies with brain imaging and blood samples to identify markers predicting response or lack of benefit of this combination.”


Nadal E, Rodriguez-Abreu D, Massuti B, et al. Single arm phase II study of atezolizumab plus chemotherapy in stage IV NSCLC with untreated brain metastases. Presented at: International Association for the Study of Lung Cancer 2021 World Conference on Lung Cancer; September 10-13, 2021; Virtual. Abstr OA09.02.

Related Videos
An expert from Dana-Farber Cancer Institute indicates that patients with prostate cancer who have 1 risk factor should undergo salvage radiotherapy following radical prostatectomy before their prostate-specific antigen level rises above 0.25 ng/ml.
An expert from Weill Cornell Medicine highlights key clinical data indicating the benefits of radium-223 in the treatment of patients with metastatic castration-resistant prostate cancer.
The risk of radionuclide exposure to the public reflects one reason urologists need to collaborate with radiation oncologists when administering radiopharmaceuticals to patients with prostate cancer.
Switching out beta emitters for alpha emitters, including radium-223, is one way to improve radiopharmaceutical treatment of prostate cancer, according to an expert from Weill Cornell Medicine.
Data demonstrate the feasibility of automated glomerular filtration rate prediction to decide between partial nephrectomy and radical nephrectomy in kidney cancer, according to an expert from the Cleveland Clinic.
Early phase trials investigating cellular therapies, bispecific antibodies, and antibody-drug conjugates for refractory kidney cancer may uncover strategies to overcome resistance mechanisms.
Increasing cancer antigen presentation as well as working with tumor cells in and delivering novel cells to the microenvironment may help in overcoming mechanisms of immune checkpoint inhibitor resistance in refractory renal cell carcinoma.
Lenvatinib plus pembrolizumab appears to be the best option for patients with refractory metastatic renal cell carcinoma who are progressing on immunotherapy combinations or are lenvatinib naïve.
Ipilimumab monotherapy does not appear effective in driving complete responses in refractory renal cell carcinoma despite yielding some progression-free survival intervals, according to an expert from the University of Texas Southwestern Medical Center.
An expert from the University of Texas Southwestern Medical Center discusses several phase 3 clinical trials supporting the use of various single-agent and combination immunotherapy regimens for advanced kidney cancer.
Related Content