n an interim analysis of expansion cohort 6 of the COSMIC-021 phase Ib
study, which included subjects with CRPC and radiological progression in
the soft tissue following enzalutamide (Xtandi) and abiraterone
(Zytiga), the objective response rate (ORR) in 44 patients who received
the combination was 32% (80% CI, 23%-42%), which included 2 (4.5%) with
complete responses and 12 (27%) with partial responses,1 said
Neeraj Agarwal, MD, who presented the data at the 2020 Genitourinary
Cancers Symposium. In addition to the 14 responses, 21 patients (48%)
had stable disease, for a disease control rate of 80%.
No new safety signals were uncovered with the combination. Only 1
patient had a grade 5 treatment-related adverse event (TRAE), which was
dehydration in a 90-year-old patient with a 6-month history of heart
failure. The overall rate of grade 3/4 TRAEs was 59%.
As single agents, cabozantinib and atezolizumab demonstrated ORRs of 5% and 0%,2,3
respectively, in metastatic CRPC. According to Agrawal, professor of
Medicine at Huntsman Cancer Center of the University of Utah in Salt
Lake City, “cabozantinib promotes an immune-permissive environment that
may enhance response to immune checkpoint inhibitors.”
The clinical activity with the combination as opposed to monotherapy “is
clearly indicative of synergy between these 2 drugs rather than merely
additive actions,” he said
The only viable option known to improve overall survival (OS) and
progression-free survival in patients with measurable disease or
soft-tissue metastases after novel hormonal therapy is taxane
chemotherapy, said Agarwal. “This combination has the potential to allow
a nonchemotherapy option for those patients who are progressing on
these earlier therapies and have limited options to date,” he said.
He continued, “When patients progress to the metastatic CRPC state after
abiraterone, enzalutamide, or even apalutamide [Erleada], the median OS
is 15 months. I think this is the most challenging patient population.”