Eligible patients in the trial had measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) per investigator assessment, had progressed on prior NHT, and could have received prior docetaxel for metastatic hormone-sensitive disease. The analysis included 132 patients with metastatic CRPC, 101 of whom were high-risk, which was defined as having measurable visceral metastases and/or extrapelvic lymphadenopathy. The median follow-up for all patients was 15.2 months, and the primary endpoint was objective response rate (ORR) by investigator per RECIST 1.1.
As previously announced, in the high-risk patient population, investigator-assessed ORR was 27%, including 2% complete responses (CRs). The Blinded Independent Radiology Committee (BIRC)-assessed ORR was 18%, all partial responses (PRs). The disease control rate (CR + PR + stable disease) was 88% by investigator assessment and 84% by BIRC assessment.
New detailed results being presented at the 2021
'These detailed results confirm previous findings from cohort 6 of COSMIC-021, further suggesting the promise cabozantinib in combination with atezolizumab may hold for patients with high-risk metastatic castration-resistant prostate cancer whose disease progressed following treatment with novel hormone therapy,' said
The safety profile was consistent with that previously observed for each single agent. No new safety signals were observed. Discontinuation of both agents due to treatment-related adverse events (AEs) occurred in 10% of patients. Frequent treatment-related AEs were diarrhea (55%), fatigue (43%), nausea (42%) and decreased appetite (34%). Grade 3 or 4 treatment-related AEs occurred in 55% of patients (of which 3% experienced grade 4 AEs), and one grade 5 treatment-related AE was reported.
Following discussions with the
'We are pleased to provide a more detailed picture at ESMO of cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer who are in need of additional treatment options,' said
About COSMIC-021
COSMIC-021 is a multicenter, phase 1b, open-label study that is divided into two parts: a dose-escalation phase and an expansion cohort phase. The dose-escalation phase was designed to enroll patients either with advanced renal cell carcinoma (RCC) with or without prior systemic therapy or with inoperable, locally advanced, metastatic or recurrent urothelial carcinoma (UC), (including renal, pelvis, ureter, urinary bladder and urethra) after prior platinum-based therapy. Ultimately, all 12 patients who enrolled in this stage of the trial were patients with advanced RCC. The dose-escalation phase of the study determined the recommended dose of cabozantinib to be 40 mg daily when given in combination with atezolizumab (1200 mg infusion once every three weeks).
In the expansion phase, the trial is enrolling 24 cohorts in 12 tumor types: RCC, UC, non-small cell lung cancer (NSCLC), CRPC, hepatocellular carcinoma (HCC), triple-negative breast cancer, epithelial ovarian cancer, endometrial cancer, gastric or gastroesophageal junction adenocarcinoma, colorectal adenocarcinoma, head and neck cancer, and differentiated thyroid cancer.
Four of the cohorts are exploratory single agent cohorts: two enrolled approximately 30 patients each with advanced UC or NSCLC, and one is enrolling approximately 80 patients with advanced CRPC to be treated with cabozantinib as a single-agent, and one enrolled approximately 10 patients with advanced CRPC to be treated with single-agent atezolizumab. Exploratory single agent cohorts have the option to be expanded up to 80 patients (cabozantinib) and 30 patients (atezolizumab) total.
About CRPC
According to the
About CABOMETYX (cabozantinib)
In the
CABOMETYX is not indicated as a treatment for metastatic CRPC.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage and prior to surgery as recommended. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.
Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.
Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.
Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 37% (16% Grade 3 and 3 times ULN (Grade ?2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ?2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ?2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab. Withhold and resume at a reduced dose based on severity.
Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity.
Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC.
Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency.
Proteinuria: Proteinuria was observed in 8% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ? Grade 1 proteinuria, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome.
Osteonecrosis of the Jaw (ONJ): ONJ occurred in
(C) 2021 Electronic News Publishing, source