Cabozantinib ( Cabometyx ) may enhance response to immune checkpoint inhibitors ( ICIs ) by promoting an immune-permissive microenvironment and has shown encouraging activity in combination with ICIs in tumor types including renal cell carcinoma ( RCC ) and hepatocellular carcinoma ( HCC ).
Cabozantinib and Atezolizumab ( Tecentriq ) have shown low objective response rates as monotherapy in metastatic castration-resistant prostate cancer ( mCRPC ) ( Smith JCO 2012; Kim JCO 2018 ).
COSMIC-021, a multinational phase 1b study, is evaluating the combination of Cabozantinib + Atezolizumab in various solid tumors.
Researchers have reported results for Cohort 6 in mCRPC.
Eligible patients were required to have radiographic progression in soft tissue after Enzalutamide and/or Abiraterone, measurable disease, and an ECOG PS of 0 or 1.
Prior chemotherapy for metastatic castration-sensitive prostate cancer ( mCSPC ) was permitted.
Patients received Cabozantinib 40 mg PO QD ( per os one a day ) and Atezolizumab 1200 mg IV Q3W ( every 3 weeks ).
CT/MRI scans were performed Q6W ( every 6 weeks ) for the first year and Q12W ( every 12 weeks ) thereafter.
The primary endpoint was overall response rate ( ORR ) per RECIST 1.1. Other endpoints included safety, ORR per immune-related RECIST ( irRECIST ), duration of response ( DOR ), progression free-survival ( PFS ), and overall survival ( OS ).
Results are presented for the first 44 patients enrolled.
Median follow-up as of Dec 20, 2019 was 12.6 months ( range 5, 20 ) for the 44 mCRPC patients.
Median age was 70 years ( range 49, 90 ), 50% had ECOG PS 1, 34% had visceral metastases, and 61% had extrapelvic lymph node metastases.
27% had prior Docetaxel and 52% had 2 prior novel hormonal therapies.
The most common any grade treatment-related adverse events ( TRAEs ) were fatigue ( 50% ), nausea ( 43% ), decreased appetite ( 39% ), diarrhea ( 39% ), dysgeusia ( 34% ), and palmar-plantar erythrodysesthesia ( 32% ).
One grade 5 TRAE of dehydration was reported in a 90-year-old.
Median duration of treatment was 6.3 months.
ORR per RECIST 1.1 among all 44 patients was 32% ( 2 complete responses [ CR: 4.5% ] and 12 partial responses [ PR: 27% ] ); 21 ( 48% ) patients had stable disease ( SD ) resulting in a disease control rate ( DCR ) of 80% in all patients.
One patient with partial disease ( PD ) per RECIST 1.1 had an immune-relate partial response ( irPR ) per irRECIST.
ORR per RECIST 1.1 was 33% in 36 patients with high-risk disease ( visceral and/or extrapelvic lymph node metastases ).
Median DOR for all patients with response per RECIST 1.1 was 8.3 months ( range 2.8, 9.8+ ).
17 ( 50% ) of 34 patients with post-baseline prostate-specific antigen ( PSA ) evaluation had a decrease in PSA.
In 12 responders with post-baseline PSA evaluation, 8 ( 67% ) had a PSA decrease greater than or equal to 50%.
In conclusion, the combination of Cabozantinib + Atezolizumab had a tolerable safety profile and demonstrated clinically meaningful activity with durable responses in men with mCRPC. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020