Durvalumab Shows Promise in Advanced Head and Neck Cancer

A phase II trial found that the immune checkpoint inhibitor durvalumab has promising clinical activity and is well tolerated both as monotherapy and in combination with tremelimumab in patients with heavily pretreated recurrent or metastatic head and neck cancer, whose tumors are PD-L1 low or negative.

“Two immunotherapies have already been approved for use in platinum-refractory recurrent or metastatic head and neck cancer, but not all patients respond to these therapies,” said Lillian Siu, MD, of the Princess Margaret Cancer Centre in Toronto, in a press release. “For immunotherapy to increase its clinical utility, it’s important that we can better identify the patients who will most likely respond to treatment.”

Siu presented results of the phase II CONDOR trial at the 2018 Multidisciplinary Head and Neck Cancers Symposium, held February 15–17 in Scottsdale, Arizona. The trial included 267 patients, randomized to receive either durvalumab plus tremelimumab (129 patients), durvalumab alone (65 patients), or tremelimumab alone (63 patients). All patients had recurrent or metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx, and were deemed PD-L1 low/negative.

The objective response rate (ORR) in the combination group was 7.8%, with 10 partial responses and no complete responses; another seven patients (5.4%) had stable disease, and the disease control rate at 6 months was 13.2%. In the durvalumab monotherapy group, the ORR was 9.2%, with six partial responses. Another four patients (6.2%) had stable disease, and the disease control rate at 6 months was 21.5%. Compared to the combination group, the odds ratio for response was no different, at 0.83 (95% CI, 0.29–2.53; P = .728).

The ORR in the tremelimumab monotherapy group was 1.6%, with only one partial response. No patients had stable disease, and the 6-month disease control rate was thus 1.6%.

In the full cohort, 59% of patients reported any treatment-related adverse event (TRAE); the most common included diarrhea (13.7%), asthenia (8.4%), and hypothyroidism (7.2%). Grade 3/4 TRAEs occurred in 15% of the full cohort, including 16% of the combination group, 12% of the durvalumab group, and 17% of the tremelimumab group. Seven patients in the combination group discontinued therapy, compared with none in the durvalumab group and five in the tremelimumab group. One patient in the combination group died after treatment-related grade 3 acute respiratory failure.

The median progression-free survival was 2 months in the combination group, compared to 1.9 months in both of the monotherapy groups. For overall survival, the median was 7.6 months with combination therapy, 6 months with durvalumab, and 5.5 months with tremelimumab.

“Our results add to the body of evidence that this immune checkpoint inhibitor is tolerable and has demonstrated encouraging clinical activity across a range of tumors, including in heavily pretreated recurrent or metastatic head and neck cancer,” Siu said.

Danielle Margalit, MD, of the Dana-Farber Cancer Institute in Boston, gave an expert perspective during a press conference. She noted that this is one of the few trials that allowed for selection of patients based on pathologic biomarkers. “These results may allow clinicians in the future to tailor immune therapy treatments based on immune markers seen on pathology,” she said.