乌鸦传媒

CHICAGO -- Adding a checkpoint inhibitor to standard chemotherapy for advanced squamous non-small cell lung cancer (NSCLC) slowed tumor progression, a researcher reported.

In a , the benefit came from adding the immunotherapeutic monoclonal antibody atezolizumab (Tecentriq) to standard treatment with carboplatin and nab-paclitaxel, according to Robert Jotte, MD, PhD, of the Rocky Mountain Cancer Centers in Denver.

On the other hand, there was no significant improvement in overall survival (OS) at an interim analysis of the , Jotte told reporters at the American Society of Clinical Oncology (ASCO) annual meeting,

Chemotherapy traditionally is thought to inhibit the immune system, but the finding suggests that adding an immunotherapeutic might overcome that, Jotte told 乌鸦传媒.

"Cytotoxic therapy can't discriminate between tumor cells and normal cells," he said, with the result that white blood cells, among others, are damaged and killed. The advantage is that, unlike the normal cells, "tumor cells don't have the inherent capability of repairing themselves."

Squamous NSCLC is difficult to treat, Jotte noted, and there have been limited new treatment options over the last few decades.

The idea of adding atezolizumab, which blocks a molecule, PD-L1 that prevents immune cells from killing tumor cells, is to "bump up" the immune system and increase its ability to attack the cancer, Jotte said.

To test the notion, Jotte's group enrolled patients with metastatic NSCLC who had not previously had chemotherapy, and assigned them to get carboplatin and nab-paclitaxel, with or without atezolizumab.

A third arm, which was not reported, used paclitaxel rather than nab-paclitaxel. Jotte told 乌鸦传媒 that arm did not meet a statistical benchmark that would have allowed it to be compared with the others.

Patients were given 4-6 cycles of treatment, followed by best supportive care for those just getting chemotherapy and maintenance therapy with atezolizumab for the other participants. The primary endpoint of the study was tumor progression or death, as assessed by the RECIST criteria for disease progression.

After a median follow-up of 17.1 months, with a minimum of 9.8 months, the 12-month landmark progression-free survival (PFS) rates were 24.7 for the patients getting atezolizumab and 12% among those on chemotherapy alone.

That translated to a median of 6.3 months without progression or death versus 5.6, which yielded a hazard ratio of 0.71.

Importantly, the benefit was across all levels of PD-L1 expression, he said, with HRs ranging from 0.44 for patients with high expression to 0.70 among those with low expression. Patients who did not have PD-L1 expression had no significant benefit, Jotte reported.

Similarly, objective response rates showed an improvement across all the PD-L1 subgroups, but not among those without PD-L1 expression.

Data for OS are immature, he said, but so far show no difference between the arms. He added that another analysis will take place later this year, and investigators hope to see a benefit.

The study "dramatically broadens the group of patients with squamous NSCLC who might benefit from adding immunotherapy to chemotherapy," commented ASCO expert David Graham, MD, of Levine Cancer Institute in Charlotte, North Carolina.

"We previously thought that you needed high levels of PD-L1 expression to benefit," he said, but Jotte's group has now shown "this is definitely not the case."

The news that their disease has progressed is "devastating" for patients with advanced NSCLC, Graham said. While the benefit in PFS seemed modest in this study, "we can double the chance that (patients) won't have to hear that bad news in the first year of their treatment."

If the survival data eventually shows a similar benefit, he said, atezolizumab plus chemotherapy could become a new standard of care.

Most patients in the study reported some adverse events related to treatment, at 94.6% for those getting atezolizumab with chemo and 90.7% for those on chemotherapy alone. Grade 3 and 4 treatment-related adverse events were reported by 68.0% and 56.9% of patients, respectively, while serious events were seen by 20.4% and 10.5%.

The bottom line was that atezolizumab and chemotherapy had a "manageable safety profile consistent with known safety risks of the individual therapies" with no new signals, Jotte said.

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