Atezolizumab OS Benefit Shown For Stage IIIB–IV Previously Treated NSCLC

The checkpoint inhibitor atezolizumab significantly improves overall survival after platinum-based chemotherapy in patients with advanced non-small-cell lung cancer

medwireNews: Patients with previously treated squamous or nonsquamous non-small-cell lung cancer (NSCLC) achieve significantly longer overall survival (OS) with the anti-programmed death-ligand 1 (PD-L1) inhibitor atezolizumab than from docetaxel therapy, OAK results demonstrate.

“Together with reports of the anti-PD1 [programmed death-1] antibodies pembrolizumab and nivolumab, our results affirm that not only the PD-1 receptor but also the ligand components (eg, PD-L1) of the pathway are valid targets for the treatment of lung cancer”, report David Gandara, from UC Davis Comprehensive Cancer Center in Sacramento, California, USA, and co-investigators.

“Targeting of PD-L1 with atezolizumab results in a clinically relevant improvement of overall survival as well as a favourable safety profile compared with docetaxel in patients with previously treated non-small-cell lung cancer, regardless of PD-L1 expression or histology.”

For the study, patients with stage IIIB or IV disease who had received one or two platinum-based cytotoxic regimens were randomly assigned to receive a 3-weekly schedule of atezolizumab 1200 mg or docetaxel 75 mg/m2 until unacceptable toxicity or disease progression.

The primary intention-to-treat analysis gave a median OS of 13.8 months for the 425 patients given atezolizumab versus 9.6 months for the 425 patients in the docetaxel-treated group, with a significant hazard ratio (HR) of 0.73.

When analysis was restricted to the 241 atezolizumab-treated patients and the 222 docetaxel-treated patients who had PD-L1 expression on at least 1% of their tumour cells or tumour-infiltrating immune cells, median OS rose to 15.7 and 10.3 months, respectively, with a significant HR of 0.74.

But patients who had low or undetectable levels of PD-L1 also derived a significant benefit from atezolizumab therapy, with a median OS of 12.6 months versus 8.9 months with docetaxel and a HR of 0.75, the investigators report in The Lancet.

And a significant HR of 0.73 for OS in favour of atezolizumab was achieved for both squamous and non-squamous NSCLC patient subgroups.

Atezolizumab was associated with fewer treatment-related grade 3 or 4 adverse events, affecting 15% versus of 43% of docetaxel-treated patients, the team adds.

Charlotte Leduc and Elisabeth Quoix, from University Hospital in Strasbourg, France, write in a linked comment that the OAK findings are “in line with previous publications, and support immune checkpoint blockers as the new standard of care for patients with non-small-cell lung cancer after failure of platinum-doublet chemotherapy.”

The OS benefit found in patients with low or undetectable PD-L1 “confirms the imperfection of this biomarker”, they say, emphasizing that it would be “unthinkable and unethical to deprive these patients of immunotherapy, even if the overall response rate and the survival benefit are lower than for patients with higher PD-L1 expression.”

Hypothesizing that the efficacy of atezolizumab in such patients might be via inhibition of CD80, the commentators conclude that “[m]ore investigations are needed to find a more specific and powerful predictive biomarker, especially in patients with low or undetectable PD-L1 expression.”

References

Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet; Advance online publication 12 December 2016. DOI: http://dx.doi.org/10.1016/S0140-6736(16)32517-X

Leduc C, Quoix E. Programmed death of chemotherapy in non-small-cell lung cancer? Lancet; Advance online publication 12 December 2016. DOI: http://dx.doi.org/10.1016/S0140-6736(16)32535-1

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