Second-Line Atezolizumab Extends Survival In Locally Advanced, Metastatic NSCLC

Compared with docetaxel, the anti-programmed death ligand 1 antibody atezolizumab significantly improves overall survival in patients with advanced non-small-cell lung cancer

medwireNews: Atezolizumab therapy imparts a survival benefit relative to docetaxel in previously treated patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC), shows the POPLAR trial.

Moreover, the level of programmed death ligand 1 (PD-L1) expression on tumour cells (TCs) and tumour infiltrating cells (ICs) is a predictor of this benefit, says the team led by Louis Fehrenbacher, from Kaiser Permanente Medical Center in Vallejo, California, USA.

Overall survival (OS) was a median of 12.6 months for the 144 patients who were randomly allocated to receive open-label atezolizumab 1200 mg on day 1 of a 21-day cycle. This was significantly longer than the 9.7 months recorded for their 143 counterparts who received docetaxel, and gave a hazard ratio (HR) of 0.73.

In this phase II trial, baseline PD-L1 expression on TCs was measured as the percentage of PD-L1-expressing total TCs (TC3≥50%, TC2≥5 and <50%, TC1≥1 and <5%, and TC0<1%), while the presence of ICs was defined as the percentage of PD-L1-positive tumour area (IC3≥10%, IC2≥5 and <10%, IC1≥1 and <5%, and IC0<1%).

And the survival benefit increased with increasing levels of PD-L1 expression – such that, atezolizumab-treated patients in the combined TC2/3 or IC2/3 subgroups had a median OS of 15.1 months compared with 7.4 months for those given docetaxel, a significant difference (HR=0.49). Similarly, median OS was 15.5 months for atezolizumab and a significantly lower 9.2 months for docetaxel in the combined TC1/2/3 or IC1/2/3 subgroups (HR=0.59).

By contrast, atezolizumab-treated patients with no PD-L1 expression on either TCs or ICs – the so-called TC0 and IC0 subgroups, respectively – had a median survival that was similar to that of docetaxel-treated participants (median of 9.7 months for both groups).

The PD-L1 inhibitor was well tolerated, say the researchers, with fewer patients in the atezolizumab versus the docetaxel arm experiencing treatment-related grade 3 or 4 side effects (11 vs 39%) and lower rates of toxicity-related discontinuation (8 vs 22%).

They conclude in The Lancet:“Together with reports of the anti-PD1 [programmed death 1] antibodies pembrolizumab and nivolumab, our results affirm that not only the receptor, but also the ligand components of the PD-L1–PD-1 axis are valid targets for the treatment of lung cancer.”

Commentators Egbert Smit and Michel van den Heuvel, both from the Netherlands Cancer Institute in Amsterdam, note that “[p]atients without PD-L1 expression did not show a benefit in overall survival as compared with docetaxel”, but they add that “the follow-up is too short to exclude the possibility that a minor subgroup might have a long-term benefit, also suggested by the objective response rate of 8% in this cohort.”

And highlighting that clinical decisions need to balance toxicities and benefit, the comment authors write: “Given the fact that toxicities of treatment with [atezolizumab] are significantly less as compared with docetaxel treatment and both treatments have a similar survival, in patients tested PD-L1 negative in the clinic one may favour treatment with [atezolizumab] over docetaxel.”

They conclude that the results “show that PD-L1 is the next immunotherapy target that will become available for clinical practice and provide some promise for the future of NSCLC treatment.”

References

Fehrenbacher L, Spira A, Ballinger M, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet 2016; Advance online publication 9 March. doi: http://dx.doi.org/10.1016/S0140-6736(16)00587-0

Smit EF, van den Heuvel MM. PD-L1 in non-small-cell lung cancer: the third target for immunotherapy. Lancet 2016; Advance online publication 9 March. doi: http://dx.doi.org/10.1016/S0140-6736(16)00700-5

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016