Cabozantinib/Atezolizumab Elicits Durable, Tolerable Clinical Activity in Advanced HNSCC

The combination of cabozantinib and atezolizumab generated rapid and durable responses in patients with advanced head and neck squamous cell carcinoma who received prior treatment with platinum-based chemotherapy.

Sylvie Rottey, MD, PhD

Sylvie Rottey, MD, PhD

The combination of cabozantinib (Cabometyx) and atezolizumab (Tecentriq) generated rapid and durable responses in patients with advanced head and neck squamous cell carcinoma (HNSCC) who received prior treatment with platinum-based chemotherapy, according to findings from cohort 17 of the phase 1b COSMIC-021 trial (NCT03170960).

Data presented at the 2022 SITC Annual Meeting showed that at a median follow-up of 25.9 months (range, 19.4-37.8), patients in cohort 17 (n = 30) achieved an objective response rate (ORR) of 17% (95% CI, 6%-35%), with a disease control rate of 60% (95% CI, 41%-77%). All 5 responders experienced a partial response; 43% had stable disease and 23% experienced progressive disease. Response information was missing or not evaluable for 5 patients.

“Patients with recurrent or metastatic HNSCC after chemotherapy have a very poor prognosis and limited therapeutic options,” lead study author Sylvie Rottey, MD, PhD, of Ghent University Hospital in Belgium, and colleagues, wrote in a poster of the data. “Here, we present outcomes in patients with platinum-pretreated HNSCC.”

Cabozantinib, a multiple receptor TKI, promotes an immune-permissive environment that may enhance the activity of immune checkpoint inhibitors.

COSMIC-021 was a multicenter trial investigating cabozantinib plus atezolizumab in patients with advanced solid tumors.

Patients were eligible to enroll to cohort 17 if they had locally advanced or metastatic HNSCC that had progressed during or following treatment with prior platinum-containing chemotherapy. Those with primary tumors in the oral cavity, oropharynx, larynx, or hypopharynx were allowed; those with primary tumors in the nasopharynx were excluded. Eligible patients needed to have received 2 or fewer prior lines of systemic anticancer therapy, which could include immune checkpoint inhibitors, EGFR-targeted therapy, and radiotherapy.

Patients in this cohort received oral cabozantinib at 40 mg daily plus intravenous atezolizumab at 1200 mg every 3 weeks. To manage adverse effects (AEs), atezolizumab infusions could be delayed, and the daily cabozantinib dose could be reduced from 40 mg to 20 mg and could be further reduced to 20 mg every other day.

The investigators performed tumor assessments by CT/MRI every 6 weeks for the first 12 months and every 12 weeks thereafter. Patients received the study treatment for as long as they experienced investigator-assessed clinical benefit or until unacceptable toxicity.

The primary end point of this trial was investigator-assessed ORR per RECIST v1.1 criteria. The secondary end point was safety, which included AEs, serious AEs, and AEs of special interest. Exploratory end points consisted of duration of response (DOR), overall survival (OS), and investigator-assessed progression-free survival (PFS) per RECIST v1.1 criteria.

In cohort 17, the median age was 62 years (range, 44-78), 83% of patients were male, and 67% had an ECOG performance status of 1. Primary tumors included oropharynx (40%), oral cavity (33%), hypopharynx (10%), larynx (7%), and other areas (10%). Additionally, 27% of patients had 1 tumor site, 30% had 2 tumors sites, and 43% had at least 3 tumor sites.

In this cohort, 10%, 50%, and 40% of patients had received 0, 1, and 2 prior lines of anticancer therapy, respectively. Overall, patients had received a median of 2.5 prior systemic anticancer agents (range, 1-10). Specifically, 30%, 97%, and 83% had received prior immune checkpoint inhibitors, radiation therapy, or surgery, respectively. A total of 60% and 50% of patients had immune cell or tumor cell PD-L1 positivity of at least 1%, respectively.

Additional data showed that the median DOR was 9.7 months (95% CI, 2.8–not evaluable). The median time to response was 2.6 months (range, 1.3-2.8). Additionally, 64% (n = 16) of the 25 patients who received at least 1 post-baseline tumor assessment experienced tumor reduction.

The median PFS and OS were 2.9 months (95% CI, 1.7-4.2) and 9.2 months (95% CI, 3.9-16.3), respectively. Study authors noted that the combination’s efficacy and patient responses were comparable across tumor cell and immune cell PD-L1 subgroups.

At data cutoff, 2 patients were still receiving the study treatment. The median duration of exposure for the combination was 3.4 months (range, 0.3-32.4), including a median duration of exposure of 3.0 months (range, 0.3-25.2) for cabozantinib and 2.9 months (range, 0-32.4) for atezolizumab.

A total of 37% and 73% of patients experienced AEs leading to cabozantinib dose reductions or cabozantinib dose holds, respectively. In addition, 47% of patients experienced AEs leading to atezolizumab dose delays.

In all, 30% and 10% of patients experienced treatment-related AEs (TRAEs) leading to discontinuation of cabozantinib and atezolizumab, respectively. Ten percent of patients experienced TRAEs leading to discontinuations of both agents.

Grade 3 or 4 TRAEs occurred in 47% of patients; no grade 5 TRAEs occurred. Grade 3 or 4 TRAEs included hypertension (17%), stomatitis (7%), mucosal inflammation (7%), decreased appetite (3%), and palmar-plantar erythrodysesthesia (3%).

Any-grade AEs of special interest occurred in 70% of patients (n = 21). These were primarily low grade and included rash (40%), hepatitis (37%), hypothyroidism (27%), pancreatitis (10%), pneuomonitis (7%), hyperthyroidism (3%), and nephritis (3%). One grade 3 or 4 event of rash, hepatitis, and pancreatitis were reported.

“These results warrant further evaluation of cabozantinib plus immune checkpoint inhibitors for the treatment of patients with HNSCC,” the study authors concluded.

Reference

Rottey S, Santoro A, Arnold S, et al. Cabozantinib plus atezolizumab in advanced head and neck cancer previously treated with platinum-containing chemotherapy: results from cohort 17 of the COSMIC-021 study. Presented at: 2022 SITC Annual Meeting; November 8-12, 2022; Boston, MA. Abstract 570

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