Lung cancer

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

Saturday, 28 Sep 2019


Atezolizumab could be a promising first line treatment option for patients with squamous or non-squamous non-small cell lung cancer with high PD-L1 expression, interim OS analysis from the IMpower110 trial suggests.

Presenting data here at the ESMO 2019 congress, Dr David R. Spigel from the Sarah Cannon Research Institute, Nashville, Tennessee, USA, 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 NSCLC, 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 1200 mg IV every three weeks until loss of clinical benefit or cisplatin or carboplatin (at investigators 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 (no cross-over was permitted).

At a median follow-up of 15.7 months atezolizumab significantly improved median OS in patients in the TC3/IC3-WT group (20.2 months vs. 13.1 months in the platinum-based chemotherapy group; HR = 0.59; 95% CI, 0.4-0.89).

“In the TC3/IC3-WT group atezolizumab also showed meaningful improvement in PFS, ORR, and DOR versus chemotherapy,” Dr Spigel told delegates.

He 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.

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

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

“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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