An ongoing randomized phase III study will compare the safety and efficacy of atezolizumab with placebo as adjuvant therapy after definitive local therapy in patients with high-risk, locally advanced squamous cell carcinoma of the head and neck.
An ongoing randomized phase III study will compare the safety and efficacy of atezolizumab (Tecentriq) with placebo as adjuvant therapy after definitive local therapy in patients with high-risk, locally advanced squamous cell carcinoma of the head and neck (SCCHN), according to a presentation at the 2018 ESMO Congress.1
The morbidity and mortality of SCCHN remain high, the authors noted, despite treatment advances. Treatment for patients with locally advanced disease often consists of combinations of surgery, radiation therapy, and chemotherapy. After this is completed, patients with SCCHN are then monitored for local recurrence and/or distant metastases.
Immunotherapies have demonstrated durable response rates and favorable safety profiles in the relapsed/refractory setting. The PD-1 inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda) are both FDA approved for patients with metastatic or recurrent SCCHN following progression on platinum-based therapy.
For the phase III IMvoke010 study (NCT03452137), the authors rationalized that by blocking PD-L1 interaction and simultaneously leaving the PD-L2/PD-1 interaction intact, atezolizumab can revive suppressed T cells to eliminate cancer cells.
Previously, the multicenter, open-label, dose-escalation and dose-expansion phase Ia PCD4989g trial (NCT01375842) evaluated atezolizumab as a single agent in patients with advanced or metastatic solid tumors or hematologic malignancies.
Thirty-two patients with previously treated head and neck cancer were administered atezolizumab intravenously (IV) every 3 weeks for 16 cycles, up to 1 year or until loss of clinical benefit. Participants were observed for safety and tolerability and assessed for response every 6 weeks.
Results showed that the overall response rate was 21%, and the median duration of response was 7.4 months (range, 2.8-45.8).2 The median progression-free survival was 2.6 months (range 0.5-48.4), while the median overall survival (OS) was 6.0 months (range, 0.5-51.6+). One-, 2-, and 3-year OS rates were 36%, 21%, and 12%, respectively.
Investigators concluded that atezolizumab demonstrated a tolerable safety profile and encouraging activity, independent of PD-L1 expression of human papillomavirus (HPV) status in patients with advanced SCCHN. This promising evidence informed the rationale for evaluating atezolizumab in patients with SCCHN in the adjuvant setting.
The phase III IMvoke010 trial will enroll about 400 patients across 18 countries, who will be randomized 1:1 to receive placebo or atezolizumab IV at a fixed dose on day 1 of each 21-day cycle for 16 cycles or up to 1 year. Investigators will then assess disease recurrence/progression and survival.3
Eligible for enrollment will be patients aged ≥18 years who have histologically or cytologically confirmed SCCHN; HPV status; completed definitive local curative therapy and scans confirming complete response, partial response, or stable disease after completion of definitive local therapy; absence of metastatic disease; and an ECOG performance status of 0 or 1.
Those who received surgery or radiotherapy alone as definitive local therapy or received prior neoadjuvant treatment of any systemic therapy without definitive local therapy are excluded. Patients with squamous cell carcinoma of the nasopharynx, evidence of disease progression or metastatic disease during or following definitive local therapy, or a history of autoimmune disease are also ineligible to enroll, as are those who received prior treatment with CD-137 agonists or checkpoint inhibitors.
The coprimary endpoints of the trial will be independent review facility (IRF)-assessed event-free survival (EFS) and OS, while secondary endpoints will be investigator-assessed EFS, IRF-assessed and investigator-assessed EFS and OS rates at specific time points, and patient-reported outcomes. Investigators will also be evaluating pharmacokinetics, immunogenicity, and biomarker studies.
The trial is currently enrolling, with an estimated primary completion date of August 28, 2023.