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SAN DIEGO -- Patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) who received atezolizumab (Tecentriq) after undergoing multimodal definitive therapy failed to achieve a statistically meaningful improvement in event-free survival (EFS) compared with patients who received placebo, a phase III trial showed.

At a median follow-up of 46.5 months, the median investigator-assessed EFS was 59.5 months with atezolizumab compared with 52.7 months with placebo (HR 0.94, 95% CI 0.70-1.26, P=0.68), with 2-year EFS rates of 67.4% and 63.8%, respectively, reported Deborah Wong, MD, PhD, of UCLA Health in Los Angeles, during the American Association for Cancer Research annual meeting.

There were also no differences between the atezolizumab and placebo groups in independent research facility-assessed EFS (59.5 vs 52.7 months; HR 0.98, 95% CI 0.73-1.32). In the intention-to-treat population, 2-year overall survival (OS) rates were 82% versus 79.2%, respectively, while 3-year OS rates were 73.8% and 72.3% (HR 0.96, 95% CI 0.68-1.36).

"Overall, these data contribute to the body of evidence regarding the limited activity of checkpoint inhibitors in an unselected patient population with locally advanced squamous cell carcinoma of the head and neck," Wong said. "The role of immunotherapy for patients with this locally advanced disease is still yet to be determined."

In discussing the rationale behind the , Wong pointed out that while treatment for locally advanced SCCHN involves a combination of surgery, radiation, and/or chemotherapy followed by routine monitoring, less than half of patients remain disease free at 2 years, with 5-year survival rates ranging from 40% to 50%.

Both chemotherapy and radiotherapy have been shown to influence the tumor immune microenvironment, including the potential to upregulate PD-1 expression, "providing a biological rationale for investigating immune checkpoint inhibitors in patients who have received these treatments," she explained. Considering atezolizumab has shown anti-tumor activity in patients with advanced, recurrent, and metastatic SCCHN, Wong and her team hypothesized it could be effective in an earlier setting.

Results Widely Anticipated

Study discussant Robert L. Ferris, MD, PhD, of the UPMC Hillman Cancer Center in Pittsburgh, noted that there have been two negative phase III studies evaluating immunotherapy/chemoradiotherapy combinations in the locally advanced SCCHN setting -- the JAVELIN Head and Neck 100 and KEYNOTE-412 trials.

However, he also pointed out that the phase II included arms in which immunotherapy was not only added concurrently to chemoradiotherapy, but sequentially as well -- similar to IMvoke010 -- and that the sequential arm demonstrated improved locoregional control and better progression-free survival and OS outcomes.

"So the IMvoke010 trial was widely anticipated by the field having seen the two negative phase III trials of concurrently adding immunotherapy, and the sequential design in the small phase II trial ... suggesting we would finally have a positive trial of [immunotherapy] in the locally advanced setting," Ferris said.

Looking at the results of IMvoke010, "I think we have to avoid getting disappointed," he added, suggesting that it might be valuable to look at how certain subgroups performed in the study.

For example, he observed that among those patients who underwent primary surgery, there appeared to be a trend toward a benefit with atezolizumab (HR 0.79, 95% CI 0.48-1.30). In an adjuvant setting for patients who had primary surgery, and therefore had minimal residual disease, immunotherapy could better improve outcomes compared with patients who weren't treated with primary surgery, he said.

He also noted that there seemed to be a trend toward a benefit with atezolizumab among HPV-positive patients (HR 0.58, 95% CI 0.22-1.49). "Perhaps targeting that group in a bigger trial that's well-powered could be beneficial," he said.

Study Details

The study was conducted at 127 sites in 23 countries and included 405 patients randomized to receive treatment with atezolizumab or placebo once every 3 weeks for up to 1 year.

More than 70% of all patients were under the age of 65, and more than 80% were men. About half of patients were enrolled from sites in Europe and the Middle East, about one-third from Asia, and less than 10% were from North America. Most were previous or current smokers, and 17% in each group were human papillomavirus (HPV)-positive.

Approximately two-thirds of patients completed the intended treatment. Among those who withdrew from treatment, most did so due to progressive disease. About 60% of patients in each arm did not receive primary surgery as part of their definitive local therapy.

Wong said that adverse events were as expected based on the known safety profile of atezolizumab.

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