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Atezolizumab Doubles Survival of NSCLC Patients With Poor PS

PARIS — Patients with untreated non–small cell lung cancer (NSCLC) who could not withstand the rigors of platinum-based chemotherapy regimens had significantly better overall survival when treated with the immune checkpoint inhibitor atezolizumab (Tecentriq), compared with their counterparts treated with either vinorelbine or gemcitabine in a phase 3 randomized trial.

Among 353 patients with treatment-naive stage 3B to 4 NSCLC who were not candidates for platinum-based chemotherapy because of poor performance status (PS), advanced age, or significant comorbidities, the median overall survival (OS) was 10.3 months for patients treated with atezolizumab vs. 9.2 months for patients assigned to receive the investigator’s choice of single-agent chemotherapy.

This difference translated into a hazard ratio for death with atezolizumab of 0.78 (P = .028), Siow Ming Lee, MD, PhD, of University College London, reported at the ESMO Congress.

The 2-year OS rate with atezolizumab was 24.3%, compared with 12.4% for single-agent chemotherapy.

“When I saw the data, I was amazed. One of four patients survived for 2 years!” he said in an interview.

The study provides encouraging evidence of a safe and effective therapy for unfit patients, those with Eastern Cooperative Oncology Group PS scores of 2 or greater, or who have substantial comorbidities that preclude their ability to receive platinum doublet or single platinum agent chemotherapy, he said.

Invited discussant Natasha Leighl, MD, MMSc, of the Princess Margaret Cancer Center, Toronto, called the study “really extraordinary. This study enrolls patients that historically are excluded or underrepresented in trials, and yet really represent the majority of patients that we diagnose and treat around the world.”

Excluded From Clinical Trials

“Cancer chemotherapy has changed the treatment landscape for the metastatic NSCLC population, but these treatments are mainly recommended for fit patients,” Lee said during his presentation of the data in a presidential symposium.

First-line pivotal trials for lung cancer patients comparing either single-agent immunotherapy or an immunotherapy/chemotherapy combination have all been conducted in fit patients, with ECOG PS of 0 or 1, he noted.

“In reality, we still have a large population of unfit NSCLC patients, of at least 40%, many of which we cannot treat with standard platinum chemotherapy. There are many elderly patients with poor performance status, and the elderly with many comorbidities, and they are frequently on many drug medications, which we see frequently in our clinic,” he said.

Study Details

To see whether immunotherapy could improve outcomes for unfit patients, investigators designed the IPSOS trial, a phase 3 multicenter open-label study of efficacy, safety, and patient-reported outcomes with atezolizumab compared with single-agent chemotherapy.

Patients from 23 centers in North America, South America, Europe, and Asia who were ineligible for platinum-based chemotherapy because of ECOG performance status of 2 or 3, or who were aged 70 or older with performance status 0 or 1 but with multiple comorbidities or other contraindications to platinum were stratified by histology, programmed death-ligand-1 (PD-L1) expression, and brain metastases, and were then randomly assigned to receive either atezolizumab 1,200 mg intravenously every 3 weeks (302 patients), or to investigator’s choice of either vinorelbine delivered orally or intravenously, according to local practice, or intravenous gemcitabine given intravenously per local practice (151 patients).

As noted before, overall survival, the primary endpoint, was significantly better with atezolizumab, translating into a 22% reduction in risk of death compared with chemotherapy.

The 1-year OS rates were 43.7% with atezolizumab vs. 36.6% with chemotherapy, and the 2-year rates were 24.3% vs. 12.4%, respectively.

­­A subgroup analysis showed trends toward better benefit for immunotherapy regardless of age, sex, race, performance status, history of tobacco use, tumor histology, stage, presence of liver metastases, number of metastatic sites, or PD-L1 expression levels. The benefit of atezolizumab was also significantly better among patients without brain metastases.

The median duration of response was 14 months with ateziluzmab vs. 7.8 months with chemotherapy. Respective objective response rates were 16.9% vs. 15.5%. Median progression-free survival, a secondary endpoint, was 4.2 months with atezolizumab and 4 months with chemotherapy, a difference that was not statistically significant. Median treatment duration was 3.5 months with atezolizumab, 2.3 months with gemcitabine, and 1.8 months with vinorelbine. Treatment-related adverse events of any grade occurred in 57% of patients on immunotherapy vs. 80.3% of those on chemotherapy. Grade 3 or 4 adverse events related to therapy occurred in 16.3% vs. 33.3%, respectively. About 13% of patients in each arm had an adverse event leading to drug discontinuation. There were three treatment-related deaths among patients on atezolizumab, and four among patients on chemotherapy. Compared with chemotherapy, atezolizumab was associated with stabilizing of health-related quality-of-life domains of functioning, and significant improvement in delaying the time to deterioration of chest pain.

Age Is Not Prognostic

“I think it’s important though to remember that in this study there are very distinct populations of patients. Poor performance status and comorbidities are prognostic, but age is not,” Leighl said in her discussion.

“In terms of current standards, performance status 3 patients are currently recommended to have best supportive care unless a targeted therapy is available for them, and while PS 2 patients have been excluded from checkpoint inhibitor trials, we treat most of these patients the same way. In this study in particular, patients had to be ineligible for platinum doublet therapy, but of course this definition was subjective,” she said.

She also commented that “if we’re now going to treat everyone with atezolizumab, I think the budget impact of this is going to be huge.”

It will be important to identify more clearly those patients aged 80 and older who might benefit from atezolizumab in this setting by better incorporating biomarkers such as PD-L1 levels to determine who can benefit from therapy and who might be spared the necessity of coming into the hospital or clinic for regular intravenous infusions, she added.

The study was supported by F. Hoffman-La Roche. Lee disclosed research funding from the company to his institution. Leighl disclosed institutional grant funding and personal fees from Roche and others.

This article originally appeared on, part of the Medscape Professional Network.

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