IMpower110: OS boost with first-line atezolizumab in PD-L1-high metastatic NSCLC
medwireNews: An interim analysis of the IMpower110 study has demonstrated an overall survival (OS) improvement with atezolizumab versus chemotherapy in treatment-naïve patients with stage IV non-small-cell lung cancer (NSCLC) and high levels of PD-L1 expression.
Reporting the findings at the ESMO Congress 2019 in Barcelona, Spain, researcher David Spigel (Sarah Cannon Research Institute, Nashville, Tennessee, USA) noted that a benefit with atezolizumab was also observed among patients with lower PD-L1 expression, but the criteria for statistical significance were not met at this stage.
“IMpower110 will continue to the OS final analysis,” he added.
In the PD-L1-high population – defined as tumor cell (TC)3 or immune-infiltrating cell (IC)3 on the Ventana SP142 immunohistochemistry assay (F Hoffmann-La Roche Ltd, Basel, Switzerland) – median OS was 20.2 months for the 107 participants who were randomly assigned to receive front-line atezolizumab 1200 mg every 3 weeks for stage IV nonsquamous or squamous NSCLC.
This was significantly longer than the 13.1 months achieved by their 98 counterparts who received four to six cycles of chemotherapy with cisplatin or carboplatin given alongside pemetrexed for those with nonsquamous histology and gemcitabine for individuals with squamous disease, equating to a significant 41% decrease in the risk for death with the PD-L1 inhibitor.
The 6-month OS rates for the atezolizumab and chemotherapy groups were 76.3% and 70.1%, respectively, with corresponding rates of 64.9% and 50.6% at the 1-year timepoint.
Atezolizumab treatment was also associated with a longer median OS in the intermediate or high expression TC2/3 or IC2/3 population, at 18.2 months compared with 14.9 months for chemotherapy (hazard ratio=0.72). However, this difference was not statistically significant, which precluded formal testing in the low, intermediate, or high expression TC1/2/3 or IC1/2/3 population, although again OS appeared to favor atezolizumab, said Spigel.
The objective response rate in the TC3 or IC3 population was higher with atezolizumab than chemotherapy, at 38.3% versus 28.6%, and the median duration of response was unreached and 6.7 months, respectively. However, the rates in the treatment arms were more comparable in the TC2/3 or IC2/3 and TC1/2/3 or IC1/2/3 populations, at 30.7% versus 32.1% and 29.2% versus 31.8%, respectively.
Spigel noted that “there were no new safety signals seen in this study, and the toxicities were expected and manageable with atezolizumab monotherapy.”
And he concluded: “Atezolizumab represents a promising first-line treatment option in patients with PD-L1-high non-small-cell lung cancer.”
Naiyer Rizvi (Columbia University Medical Center, New York, USA), who discussed the results at the Congress, agreed that atezolizumab is a new standard of care for this patient population, in addition to pembrolizumab.
He added, however, that unanswered questions remain, such as the outcomes when the 22C3 pharmDx assay (Agilent, Santa Clara, California, USA) is used for delineating the PD-L1 expression groups, and the outcomes for just the TC2 or IC2 population.
Rizvi said that he would also be interested to see the data for the TC3 and IC3 populations separately, as previous research in the second-line setting points to variance in response between these groups.
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