Monotherapy with the checkpoint inhibitor atezolizumab demonstrated promising efficacy in patients with advanced head and neck cancer that was independent of both PD-L1 expression status on immune cells and the presence of human papilloma virus (HPV) infection, according to findings presented during ESMO 2017, the Annual Congress of the European Society for Medical Oncology in Madrid, Spain.
Atezolizumab is an anti–PD-L1 checkpoint inhibitor that restores tumour-specific T-cell immunity by blocking the binding of PD-L1 to both PD-1 and B7.1.
Rastislav Bahleda of the Early Drug Development Department, Gustave Roussy in Villejuif, France presented data from this phase Ia study (NCT01375842) evaluating the safety and clinical activity of single-agent atezolizumab in patients with advanced head and neck cancer.
The first 10 patients were non-selectively enrolled; however, upon identification of PD-L1 as a potential biomarker, subsequent enrolment was based on PD-L1 status of > 5% expression on immune cells (IC2/3) as detected by immunohistochemistry using the VENTANA SP142 antibody. Determination of HPV status was made by PCR.
Of the 32 enrolled patients, 84% were male with a median age of 62 years (range 32 to 78 years), 66% of patients were ECOG performance status 1, and the majority (66%) of patients reported current or previous tobacco use. All patients had been heavily pre-treated, with 53% of patients receiving ≥ 2 prior lines of therapy. Most (56%) patients had a primary tumour in the oropharynx and other common primary tumour sites included the oral cavity in 22%, and nasopharynx in 13% of patients.
Atezolizumab was initially administered intravenously every 3 weeks for 16 cycles or up to 1 year but patients were subsequently treated until loss of clinical benefit was observed.
Atezolizumab monotherapy was safe in patients with head and neck cancer
The primary endpoint of this study was safety.
The duration of follow-up was 14 months or more and the median treatment duration was 3.4 months.
Most (66%) patients experienced a treatment-related adverse event (TRAE). Grade 3 TRAEs of tumour lysis syndrome, hyponatremia, pruritus, and colitis occurred in 3 (9%) patients. One (3%) patient had grade 4 treatment-related cardiac tamponade.
No grade 5 TRAEs were seen.
Atezolizumab showed activity in the overall population and in subgroups of patients with low to no and higher PD-L1 expression status
PD-L1 expression in immune cells was <5% (IC0/1) in 7 patients and >5% (IC2/3) in 25 patients. In all patients, regardless of PD-L1 expression, the confirmed objective response rate (ORR) by RECIST v1.1. was 22%; median progression-free survival (PFS) was 2.6 months (range 0.5 to 48.4 months) and median overall survival (OS) was 6.0 months (range 0.5 to 51.6+ months).
The subgroup of 25 IC2/3 patients with higher PD-L1 expression demonstrated an ORR of 24% that consisted entirely of partial responses, and the disease control rate (DCR) was 28%. In responding patients, the median duration of response (DoR) was 26.2 (range 2.8 to 45.8) months.
In the subgroup of 7 patients with low PD-L1 expression, the ORR was 14%, which represented one partial response. The DCR was 43% and the DOR was 7.4 months in responding patients.
The authors concluded that atezolizumab was well-tolerated in patients with advanced head and neck cancer. Encouraging responses and long-term survival were observed. These findings warrant further investigation.
The study was supported by F. Hoffmann-La Roche Ltd.
1044O – Bahleda R, et al. Long-Term Safety and Clinical Outcomes of Atezolizumab in Head and Neck Cancer: Phase Ia Trial Results.