番茄社区

CHICAGO -- Adding a checkpoint inhibitor to standard therapy for advanced non-squamous non-small cell lung cancer (NSCLC) lowered the risk of death by 22% in patients getting their first line of therapy, a researcher reported here.

In a randomized phase III trial, investigators added the anti-PD-L1 immunotherapeutic atezolizumab (Tecentriq) to standard treatment with bevacizumab (Avastin) and a platinum doublet, according to Mark Socinski, MD, of the Florida Hospital Cancer Institute in Orlando.

The four-drug combination, compared with bevacizumab and carboplatin/paclitaxel, also slowed disease progression, Socinski reported at the American Society of Clinical Oncology (ASCO) annual meeting. Findings from the IMpower150 study were simultaneously published in the .

The finding is encouraging for patients, commented Hossein Borghaei, DO, of Fox Chase Cancer Center in Philadelphia.

"It's always good news when we can improve on overall survival, response and PFS [progression-free survival] in patients who have incurable cancers," Borghaei told 番茄社区.

As immunotherapeutic drugs have developed in recent years, he said, "we have been asking for overall survival data" -- information that's now available for this investigational four-drug regimen. "This is an important step in the right direction," Borghaei said.

On the other hand, he noted, adding another drug to what is now a standard regimen will likely increase the cost of treatment, and there are additional side effects to watch for, although "I don't see a side effect profile that is different from what was anticipated."

Atezolizumab, a monoclonal antibody against the programmed cell death-ligand 1 (PD-L1) protein, is

In the front-line setting, the researchers hypothesized that atezolizumab might have its anti-tumor activity enhanced by bevacizumab, which blocks the immunosuppression mediated by the vascular endothelial growth factor (VEGF).

To test the idea, they enrolled patients with metastatic non-squamous NSCLC who had not previously had chemotherapy and assigned them to get bevacizumab, carboplatin, and paclitaxel, with or without atezolizumab. A third arm, which was not reported, substituted atezolizumab for bevacizumab in combination with the chemotherapy.

All told, 1,202 patients enrolled and formed the intention to treat population. Of those, 1,040 had wild-type genetics (those with certain mutations were excluded from the efficacy analysis), and 365 were randomly assigned to get the four-drug combination while 336 got the bevacizumab combination.

The study had two primary endpoints:

• The rate of PFS among patients whose tumor had wild-type genetics and the rate of PFS among wild-type patients with a high effector T-cell signature (Teff) in the tumor.
• Overall survival (OS) in the wild-type population.

After a median follow-up of 15.4 months in the atezolizumab group and 15.5 months in the bevacizumab, 517 patients had disease progression or died, including 241 of 356 patients and 276 of 336 patients, respectively.

Median PFS was 8.3 months in the atezolizumab group, significantly longer than the 6.8 months in the bevacizumab group, yielding a stratified hazard ratio of 0.62 for disease progression or death .

In the Teff-high population, 200 of the 284 patients in the combined groups had disease progression or died, including 97 of 155 patients in the atezolizumab group and 103 of 129 in the bevacizumab group.

Median PFS was 11.3 months for atezolizumab patients, significantly longer than the 6.8 months in the bevacizumab group, yielding a stratified HR 0.51.

The median OS among the patients in the wild-type population was longer in the atezolizumab group than in the bevacizumab group at 19.2 months versus 14.7 months, leading to a HR 0.78 for death.

The safety profile of the four-drug combination, the investigators reported, held no surprises -- it was essentially the sum of the known safety signals of the individual medications.

In an earlier ASCO presentation, some of the same researchers reported positive preliminary results from a study of atezolizumab as front-line therapy in squamous NSCLC.