Atezolizumab doubles 3-year survival rate vs docetaxel in NSCLC
Even in the long term, atezolizumab shows significant survival benefit over docetaxel for patients with locally advanced or metastatic non-small–cell lung cancer (NSCLC) who have previously been treated, regardless of PD-L1 expression levels or tumour histology, according to the POPLAR* study presented at the 2018 European Lung Cancer Congress (ELCC).
Landmark analysis at 2 years showed that the rate of overall survival (OS) was doubled with atezolizumab compared with docetaxel (OS rate, 32.2 percent vs 16.6 percent; p=0.0027). Similarly, almost twice as many patients were alive at 3 years in the atezolizumab group vs the docetaxel group (OS rate, 18.7 percent vs 10.0 percent; p=0.0419). [ELCC 2018, abstract 136PD_PR]
“Nearly one in five patients treated with atezolizumab was alive at 3 years. This places atezolizumab among the drugs with the highest landmark OS in previously treated lung cancer patients,” said lead author Dr Julien Mazières of Toulouse University Hospital in Toulouse, France.
“Before immunotherapy, the long-term survival of NSCLC patients was close to zero percent,” said invited discussant Professor Solange Peters from Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland. “POPLAR supports the concept that long-term survival is possible with immunotherapy … These latest results are exciting because … [the study] provides convincing proof that long-term survival now exists in lung cancer.”
The long-term survival benefit that atezolizumab had over docetaxel was observed regardless of PD-L1 expression levels, with the greatest benefit seen in the patient subgroup with PD-L1 expression in ≥50 percent of tumour cells or ≥10 percent of tumour-infiltrating immune cells (OS rates, 41.7 percent vs 19.9 percent; p=0.1003 at 2 years and 37.5 percent vs 14.9 percent; p=0.0724 at 3 years). Even those with <1 percent PD-L1 expression in both types of cells benefitted more from atezolizumab than docetaxel (p=0.0202 and p=0.0693 at 2 and 3 years, respectively).
“The fact that all subgroups of patients benefitted to a similar degree is good in the sense that atezolizumab can be tried in all advanced NSCLC patients,” said Mazières. “On the other hand, it means that we cannot predict which patients are most likely to live for 3 years. We need to find biomarkers to help us identify the long-term survivors with the drug.”
The 3-year data from the POPLAR trial represent the longest follow-up to date with anti-PD-L1 immunotherapy in NSCLC patients who were previously treated. The intention-to-treat population consisted of 287 patients, who were randomized 1:1 to intravenous atezolizumab 1200 mg or docetaxel 75 mg/m2 Q3W.
The objective response rate was 15 percent in both the atezolizumab and the docetaxel groups, but the response duration was threefold longer with atezolizumab (median, 22.3 vs 7.2 months).
Safety profile was also more favourable with atezolizumab compared with docetaxel, consistent with previous reports. [Lancet 2017;389:255-265; Lancet 2016;387:1837-1846]
Outlook for immunotherapy in NSCLC
According to Peters, there is currently a strong argument for using immunotherapy in patients with advanced NSCLC. “In the nivolumab phase I trial, 15 percent of patients were alive at 5 years, which in cancer is usually considered being cured. We should offer all patients this one in six chance of five-year survival,” said Peters. “However, this poses a financial challenge for healthcare systems.”
For the strategy to be sustainable, Peters underscored the importance of patient selection and proposed possible methods of achieving this. “That would enable us to treat only the patients with a high chance of long-term survival with immunotherapy.”
“POPLAR shows that PD-L1 is not a useful biomarker to exclude patients from immunotherapy, since some patients with very low expression had an OS benefit. Rather than a single biomarker, I think it will be a signature of many biomarkers including tumour mutation burden that identifies the patients who should not be treated,” she continued.
Characterizing the long-term survivors of previous trials with atezolizumab, nivolumab, and pembrolizumab in terms of demographics, tumour mutation burden, expression of immune genes, PD-L1 expression, and smoking status would be important first step towards defining the criteria for patient selection, suggested Peters.
“Focusing future studies on these patients will help us to discover a biomarker signature for use in clinical practice,” she said.