Durvalumab alone or with tremelimumab appeared tolerable and showed slowed tumor growth among heavily pretreated patients with recurrent or metastatic head and neck cancer whose tumors had low or negative PD-L1 expression, according to results from the CONDOR trial scheduled for presentation at the Multidisciplinary Head and Neck Cancers Symposium.
Previously, the phase 2 HAWK trial showed durvalumab (Imfinzi, AstraZeneca) to be safe and effective among patients with head and neck tumors that expressed high levels of PD-L1.
Lillian Siu, MD, senior medical oncologist at Princess Margaret Cancer Centre and professor of medicine at University of Toronto, and colleagues studied 267 patients with nonrespondent metastatic (64%) or recurrent (36%) cancer of the oral cavity, oropharynx, hypopharynx or larynx who had low or negative expression of PD-L1 (< 25% of tumor cells). Researchers randomly assigned patients 1:1:2 to durvalumab alone (n = 67), tremelimumab (MedImmune) alone (n = 67) or combination therapy (n = 133).
“These two drugs in combination have preclinical synergy, as well as clinical demonstration of enhanced activity,” Siu said in a press conference. “Therefore, it makes sense for these two pathways that are not redundant to be combined together in the setting of the CONDOR study in PD-L1-low or -negative patients where there is clearly a clinically unmet need.”
Researchers stratified patients by HPV (28.1%) and smoking status.
Median follow-up was 5.8 months.
Researchers reported overall response rates of 9.2% (95% CI, 3.5-19) for durvalumab alone, 7.8% (95% CI, 3.8-13.8) for combination therapy and 1.6% (95% CI, 0.4-8.5) for tremelimumab alone. Ten of the 17 observed partial responses remained ongoing as of March 31, 2017.
PFS was 2 months (95%, 1.9-2.1) for combination therapy and 1.9 months for both durvalumab alone (95% CI, 1.8-2.8) and tremelimumab alone (95% CI, 1.8-2).
Median OS was 7.6 months (95% CI, 4.9-10.6) for combination therapy compared with 6 months (95% CI, 4-11.3) for durvalumab and 5.5 months (95% CI, 3.9-7) for tremelimumab.
Researchers observed consistent safety profiles with durvalumab alone and in combination compared with similar immunotherapeutic agents.
Adverse events occurred among 63% of patients treated with durvalumab alone, 58% of those treated with durvalumab plus tremelimumab, and among 55% of the tremelimumab-alone group. Adverse events included diarrhea (13.7%), fatigue (9.1%), asthenia (8.4%), hypothyroidism (7.2%), decreased appetite (6.1%), rash (5.7%), nausea (4.9%), pruritus (4.9%), pyrexia (3.8%), anemia (3.4%) and vomiting (3%).
Grade 3 or grade 4 adverse events occurred most frequently in the tremelimumab arm (16.9%) followed by with durvalumab plus tremelimumab (15.8%) and durvalumab alone (12.3%). These included diarrhea (2.7%), fatigue (1.5%), anemia (1.1%) and asthenia (1.1%). Twelve patients — including seven in the combination arm and five in the tremelimumab arm — discontinued therapy due to an adverse event. One treatment-associated death occurred in the combination arm.
“Both the combination arm as well as the durvalumab arm exhibited very manageable toxicity profiles and clearly these are regimens of interest in a patient population where there are very few treatment options,” Siu said during the press conference.
“In the phase 2 CONDOR trial, durvalumab, an investigational PD-L1 inhibitor, showed an [ORR] consistent with other single-agent PD-1/PD-L1 inhibitors in second-line settings for head and neck cancer,” Siu said in a press release. “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.”
A phase 3 study of durvalumab alone and in combination among patients with both PD-L1 high and PD-L1 low/negative recurrent metastatic head and neck cancer is underway. – by Cassie Homer
Sui L, et al. Abstract 1. Presented at Multidisciplinary Head and Neck Cancers Symposium; Feb. 15-17, 2018; Scottsdale, Ariz.
Disclosures: AstraZeneca funded this study. Siu reports research funding from Novartis, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim and stock options in Agios, AstraZeneca/MedImmune, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Entremed, Genentech/Roche, GlaxoSmithKline, Merck, Novartis and Pfizer. Please see the abstract for all other researchers’ relevant financial disclosures.