Atezolizumab shows OS benefit over chemo in PD-L1 high NSCLC

Lung cancer

By Nicola Garrett

1 Oct 2019

Atezolizumab is a promising first line treatment option for patients with PD-L1 high NSCLC, interim OS analysis from the IMpower110 trial suggests.

Presenting data at the European Society for Medical Oncology (ESMO) 2019 congress in Barcelona, Dr David R. Spigel from the Sarah Cannon Research Institute, Nashville, Tennessee, told delegates that the PD-L1 inhibitor demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit in people with high PD-L1 expression, compared with platinum based chemotherapy alone.

The trial initially included 572 patients, but patients with ALK or EGFR mutations were removed for the analysis, leaving 555 wild-type (WT) patients.

All patients had PD-L1 expression of at least 1% on tumour cells (TC) or tumour-infiltrating immune cells (IC); measurable disease; and ECOG performance status of 0 or 1.

The primary endpoint of the trial was OS in the WT population by PD-L1 subgroup (TC3 or IC3 WT ≥50% TC or ≥10% IC; TC2/3 or IC2/3 WT ≥5% TC or IC; TC1/2/3 or IC1/2/3 WT ≥1% TC or IC), with key secondary endpoints of progression-free survival (PFS), overall response rate (ORR), and duration of response (DOR).

Patients were randomised 1:1 to receive: atezolizumab 1,200 mg IV, atezolizumab every three weeks until loss of clinical benefit (as assessed by the investigator) or cisplatin or carboplatin (per investigator discretion) combined with either pemetrexed (non-squamous) or gemcitabine (squamous), followed by maintenance therapy with pemetrexed alone (non-squamous) or best supportive care (squamous) until disease progression, unacceptable toxicity or death.

Results showed that atezolizumab significantly improved median OS in patients in the TC3/IC3-WT group (20.2 months vs. 13.1 months; HR = 0.59; 95% CI, 0.4-0.89).

Atezolizumab also showed an OS benefit in the TC2/3 or IC2/3 group (18.2 months vs. 14.9 months; HR = 0.72; 95% CI, 0.52-0.99) but did not reach clinical significance.

In the TC3/IC3-WT group atezolizumab also showed meaningful improvement in PFS, ORR, and DOR versus chemotherapy.

Dr Spigel noted that because the OS testing boundary was not crossed in the TC2/3 or IC2/3 WT population, the TC1/2/3 or IC1/2/3 WT population was not formally tested.

The trial will continue through its final analysis, which will include patients with lower PD-L1 expression levels, Dr Spigel told the congress.

Atezolizumab’s safety profile appeared consistent with prior observations, and no new safety signals were identified, he said.

“Importantly, additional biomarker analyses will be presented at future meetings, including ongoing work with other assays to measure PD-L1 expression … as well as tumour mutation burden data specifically in the blood,” he added.

The study was funded by F. Hoffmann-La Roche.

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