Atezolizumab Shows First-Line Potential For Advanced Nonsquamous NSCLC Brain Metastases

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Phase II trial findings suggest that the use of atezolizumab alongside carboplatin and pemetrexed may improve the survival of patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) and untreated asymptomatic brain metastases. 

The treatment regimen in the ATEZO-BRAIN study achieved progression-free survival (PFS) “similar” to that reported in the KEYNOTE-189 trial among participants with brain metastases, said Ernest Nadal, from Institut Català d’Oncologia, L’Hospitalet in Barcelona, Spain, at the World Congress on Lung Cancer 2021 virtual meeting. 

The present trial included 40 treatment-naïve patients without an EGFR or ALK sensitising mutation and with any level of PD-L1 expression. Baseline use of anticonvulsants and a dexamethasone dose of up to 4 mg/day was permitted, with the latter used by 43.0% of the group. The patients were aged a median 62.6 years and most were male (72.5%) and current or former smokers (75.0%).  

The participants received 4–6 cycles of carboplatin plus pemetrexed chemotherapy and atezolizumab 1200 mg every 3 weeks, followed by maintenance doses of pemetrexed and atezolizumab every 3 weeks for up to 2 years or until tumour progression or unacceptable toxicity. However, patients with only intracranial metastases who experienced progression could continue treatment after brain radiotherapy. 

The trial design used a 12-week PFS rate of 50% – based on a historical rate of 40% achieved with chemotherapy alone – and a 35% grade 3–4 treatment-related adverse event (TRAE) rate as a checkpoint; the study continued after this point as the boundaries for both futility and unacceptable toxicity were unreached, explained Ernest Nadal. 

Indeed, the 12-week PFS rate with atezolizumab was 60.0% and the grade 3–4 toxicity rate was 27.5%. Three TRAEs occurred at grade 4 – thrombocytopenia, neutropenia and hallucinations – and there were no fatal TRAEs. 

The most common immune-related AEs of any grade were anorexia (20%), skin rash (20%) and increases in alanine transaminase (ALT, 13%) and aspartate aminotransferase (13%), with a grade 3 increase in ALT occurring in 3%. Pneumonitis at any-grade occurred in 5% and at grade 3 in 3%. 

Overall, the median number of carboplatin cycles was four, while patients received a median 8.5 cycles of both pemetrexed and atezolizumab. 

After a median 17.3 months of follow-up, the median systemic PFS duration was 8.9 months, with 24.9% achieving PFS at 18.0 months. The corresponding rates for intracranial PFS were 6.9 months and 10.4%. 

Turning to the secondary endpoints, Ernest Nadal gave objective response rates for systemic and intracranial responses of 47.5% and 40.0%, respectively, and this included the 10% of patients with a complete response in the brain. 

Four patients had discordant responses, where two patients experienced progressive systemic but stable intracranial disease and two had a partial response systemically but progressive brain disease. 

Median OS was 13.6 months, with 32% of patients alive at 2 years, a finding that he described as a “clinical benefit” from the use of atezolizumab plus chemotherapy. 

“The safety profile and efficacy of atezolizumab combined with carboplatin and pemetrexed is favorable in patients with NSCLC and untreated brain metastases, including those receiving corticosteroids”, summarised Ernest Nadal. 

He added that “correlative studies with brain imaging and blood samples are currently ongoing.” 

Reference  

Nadal E, Rodríguez-Abreu D, Massutí B, et al. Atezo-Brain: Single arm phase II study of atezolizumab plus chemotherapy in stage IV NSCLC with untreated brain metastases. 2021 World Conference on Lung Cancer; 8–14 September