New research shows that combination therapy with cabozantinib and atezolizumab (T drug) produced a rapid and durable anti-cancer response in patients with advanced head and neck squamous cell carcinoma who had previously received platinum-based chemotherapy.
According to data from cohort 17 of the Phase 1b COSMIC-021 trial (NCT03170960), the combination of cabozantinib and ateleizumab, at a mean follow-up length of 25.9 months, 17% of the 30 patients in cohort 17 had significant tumour shrinkage or disappearance, resulting in an overall disease control rate of 60% when those with stable lesions were added. five patients with tumours in remission All of the patients whose tumours had shrunk by at least 30%.
"Patients with recurrent or advanced squamous cell carcinoma of the head and neck after platinum-based chemotherapy have a very poor prognosis and limited treatment options," said the study's lead author, Dr Sylvie Rottey of Ghent University Hospital in Belgium, and colleagues.
Cabozantinib is a multi-receptor TKI-targeting agent that enhances the activity of immune checkpoint inhibitors such as PD-1 and PD-L1.
COSMIC-021 is a multicentre trial investigating the effects of cabozantinib in combination with atelizumab in patients with advanced solid tumours.
Patients are eligible for cohort 17 if they have locally advanced or advanced squamous cell carcinoma of the head and neck and have disease progression during or after platinum-based chemotherapy. Patients with head and neck cancer with primary tumours of the oral cavity, oropharynx, larynx or hypopharynx were accepted for enrolment, but patients with primary tumours of the nasopharynx were excluded.
Patients in this cohort received 40 mg of oral cabozantinib daily and 1200 mg of intravenous atelelizumab every 3 weeks. To control adverse events (AEs), the infusion of atelizumab could be delayed and the daily dose of cabozantinib could be reduced from 40 mg to 20 mg.
The investigators performed tumour assessments by CT / MRI every 6 weeks for the first 12 months and every 12 weeks thereafter.
The primary endpoint of the trial is the rate of tumour remission in patients, and the secondary endpoint is safety, including adverse events, serious adverse events, etc. Other endpoints of the trial, also included duration of remission (DOR), overall survival (OS) and progression-free survival (PFS) as assessed by the investigators according to RECIST v1.1 criteria.
Overall, the mean number of prior systemic drug treatments received by patients participating in the trial was 2.5 (range 1-10). Specifically, 30%, 97% and 83% of patients had received immune checkpoint inhibitors, radiation therapy or surgery respectively. A total of 60% and 50% of patients had a PD-L1 positivity rate of at least 1% for immune or tumour cells.
Data from the trial showed that patients were treated for a mean duration of 9.7 months if their tumour was in remission. In addition, 64% (16) of the 25 patients who underwent tumour evaluation after receiving at least 1 treatment experienced tumour shrinkage.
Regarding safety, grade 3 or 4 adverse reactions occurred in 47% of patients, specifically, hypertension, stomatitis, mucosal inflammation and decreased appetite.
Low grade adverse reactions occurred in 70% of patients and included rash, hepatitis, hypo/hyperthyroidism, pancreatitis, and pneumonia.
"These outcome results suggest that there is value in further evaluating cabozantinib in combination with immune checkpoint inhibitors for the treatment of patients with advanced head and neck squamous cell carcinoma."
