Phase II Trial of Atezolizumab Combined With Carboplatin and Pemetrexed for Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer With Untreated Brain Metastases (Atezo-Brain, GECP17/05)

Author(s): Ernest Nadal, MD, PhD^1,2; Delvys Rodríguez-Abreu, MD³; Marta Simó, MD, PhD⁴; Bartomeu Massutí, MD, PhD⁵; Oscar Juan, MD, PhD⁶; Gerardo Huidobro, MD⁷; Rafael López, MD⁸; Javier De Castro, MD, PhD⁹; Anna Estival, MD, PhD¹⁰; Joaquín Mosquera, MD¹¹; Ivana Sullivan, MD, PhD¹²; Enriqueta Felip, MD, PhD¹³; Ana Blasco, MD¹⁴; Maria Guirado, MD¹⁵; Eva Pereira, BoS¹⁶; Noelia Vilariño, MD^1,2,4; Valentín Navarro, PhD¹; and Jordi Bruna, MD, PhD⁴

Source: DOI: 10.1200/JCO.22.02561 Journal of Clinical Oncology 41, no. 28 (October 01, 2023) 4478-4485

Dr. Anjan Patel's Thoughts

A nicely done Spanish study showing that in metastatic NSCLC, asymptomatic patients with brain metastases can have radiation therapy deferred.

Starting with systemic therapy was found to be reasonable and effective, validating a common practice. Patients were treated with atezolizumab + carboplatin + pemetrexed + steroids, and any number of brain mets was allowed as long as they had at least one 10mm in size or greater. This study excluded patients harboring EGFR/ALK driver mutations.

PURPOSE

The Atezo-Brain study evaluated atezolizumab combined with chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC) with untreated brain metastases, a population traditionally excluded from trials.

METHODS

This single-arm phase II clinical trial enrolled patients with advanced nonsquamous NSCLC with untreated brain metastases without neurologic symptoms or asymptomatic with medical treatment. Dexamethasone was allowed up to 4 mg once daily. Atezolizumab plus carboplatin and pemetrexed was given for four to six cycles followed by atezolizumab plus pemetrexed until progression for a maximum of 2 years. The primary end points were to determine the progression-free survival (PFS) rate at 12 weeks and the incidence of grade ≥3 adverse events during the first 9 weeks. Intracranial outcomes were assessed using response assessment in neuro-oncology brain metastases criteria.

RESULTS

Forty patients were enrolled and 22 (55%) were receiving corticosteroids at baseline. The overall 12-week PFS rate was 62.2% (95% credibility interval [CrI], 47.1 to 76.2). The rate of grade 3/4 adverse events during the first 9 weeks was 27.5%. Most neurologic events were grade 1 and 2 but five patients (12.5%) experienced grade 3-4 neurologic events. With a median follow-up of 31 months, intracranial median PFS was 6.9 months and response rate was 42.7% (95% CrI, 28.1 to 57.9). Systemic median PFS was 8.9 months and response rate was 45% (95% CrI, 28.1 to 57.9). The median overall survival (OS) was 11.8 months (95% CI, 7.6 to 16.9) and the 2-year OS rate was 27.5% (95% CI, 16.6 to 45.5).

CONCLUSION

Atezolizumab plus carboplatin and pemetrexed demonstrates activity in patients with advanced nonsquamous NSCLC with untreated brain metastases with an acceptable safety profile.

Author Affiliations

¹Department of Medical Oncology, Institut Català d’Oncologia (ICO), L’Hospitalet de Llobregat, Barcelona, Spain; ²Preclinical and Experimental Research in Thoracic Tumors (PReTT) Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain; ³Department of Medical Oncology, Complejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain; ⁴Neuro-Oncology Unit, Hospital Universitari de Bellvitge-ICO, IDIBELL, L’Hospitalet, Barcelona, Spain; ⁵Department of Medical Oncology, Hospital General de Alicante, Alicante, Spain; ⁶Department of Medical Oncology, Hospital Universitari La Fe, Valencia, Spain; ⁷Department of Medical Oncology, Complejo Hospitalario Universitario de Vigo, Vigo, Spain; ⁸Department of Medical Oncology, Hospital Clínico de Valladolid, Valladolid, Spain; ⁹Department of Medical Oncology, Hospital Universitario La Paz, Madrid, Spain; ¹⁰Department of Medical Oncology, Institut Català d’Oncologia (ICO), Badalona, Spain; ¹¹Department of Medical Oncology, Hospital Universitario A Coruña, A Coruña, Spain; ¹²Department of Medical Oncology, Hospital Sant Pau, Barcelona, Spain; ¹³Department of Medical Oncology, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona, Spain; ¹⁴Department of Medical Oncology, Hospital General de Valencia, Valencia, Spain; ¹⁵Department of Medical Oncology, Hospital Universitario de Elche, Elche, Spain; ¹⁶Spanish Lung Cancer Group, Barcelona, Spain

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