Lung cancer

Adjuvant immunotherapy in early-stage NSCLC: ‘watch this space’

Eagerly-awaited overall survival findings for adjuvant atezolizumab immunotherapy in patients with non-small cell lung cancer (NSCLC) suggest the benefit may be confined to people with high levels of tumour PD-L1 expression.

The significant benefits previously seen in disease-free survival with atezolizumab over best supportive care (BSC) in the phase 3 IMPower010 trial were not replicated in an interim analysis of OS results presented at the IASLC World Conference on Lung Cancer 2022 in Vienna .

While there was an OS trend in favour of atezolizumab in the PD-L1 TC > 1% stage II-IIIA population (OS HR, 0.71 [95% CI: 0.49, 1.03]), this was not significant and it was not seen in the all randomised stage II-IIIA or intent-to-treat population, according to study investigators.

After median follow-up of 45 months in a study involving 1005  patients who received atezolizumab or placebo after chemotherapy, the highest magnitude of OS improvement was observed in those whose tumours expressed PD-L1 TC≥50% (HR=0.43, 95% CI: 0.24-0.78), they noted.

In this patient group, OS was 84.8% at 60 months for atezolizumab (n = 106) compared with 67.5% with BSC ( n = 103).

The study investigators said the interim findings suggested the secondary outcome data for OS were not mature, but nevertheless the results in patients with high levels of tumour PD-L1 expression were “of clinical interest in this curative setting.”

“This OS analysis shows a promising trend in favour of atezolizumab over [best supportive care] in the PD-L1 TC ≥1%, stage II–IIIA population and a clinically meaningful improvement in the PD-L1 TC ≥50%, stage II–IIIA population, with the OS improvements observed across most subgroups,” said Dr Enriqueta Felip of the Vall d’Hebron Institute of Oncology, Barcelona.

Atezolizumab was approved by the FDA as adjuvant treatment after complete resection and platinum-based chemotherapy in patients with PD-L1 tumour cell (TC) ≥1% stage II-IIIA NSCLC based on the previous DFS results. However in the EU it was approved in PD-L1 TC ≥50% stage II-IIIA NSCLC.

In a discussion at the IASLC meeting, Dr Benjamin Besse, medical oncologist at the Gustave Roussy Institute, France, said the survival curves for atezolizumab and control in the trial appeared to be separating, but long follow up was required.

He said further analysis of subgroups of PD-L1 may help inform which patients will benefit most from adjuvant therapy with atezolizumab and this may be better informed by liquid biopsy ctDNA analysis.

In the IMPower010 study, eligible patients had completely resected stage IB (tumours ≥4 cm)-IIIA NSCLC (AJCC/UICC v7) and ECOG PS 0-1. Patients received one to four, 21-day cycles of cisplatin-based doublet chemotherapy and were subsequently randomised 1:1 to receive 16 cycles of atezolizumab 1200 mg once every three weeks or best supportive care.

Adverse events of Grade 3-4 occurred in 22% of the atezolizumab arm and 11.5% of the best supportive care arm and led to atezolizumab discontinuation in 18.2% of patients. Grade 5 treatment-related adverse events occurred in 0.8% of patients who received atezolizumab and 0% in the best supportive care arm. Adverse events of special interest occurred in 52.1% of atezolizumab-treated patients, 7.9% were Grades 3-4.

The study was funded by Roche and Genentech. 

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