The FDA ( U.S. Food and Drug Administration ) has granted accelerated approval to Tecentriq ( Atezolizumab ) for the treatment of people with locally advanced or metastatic urothelial carcinoma ( mUC ) who have disease progression during or following Platinum-based chemotherapy, or whose disease has worsened within 12 months of receiving Platinum-based chemotherapy before surgery ( neoadjuvant ) or after surgery ( adjuvant ).
Urothelial carcinoma accounts for 90% of all bladder cancers and can also be found in the renal pelvis, ureter and urethra.
Roche is also evaluating Tecentriq in a confirmatory phase III study ( IMvigor 211 ), which compares Tecentriq to chemotherapy in people whose bladder cancer has progressed on at least one prior Platinum-containing regimen.
IMvigor 210 is an open-label, multicenter, two-cohort phase II study that evaluated the safety and efficacy of Atezolizumab in people with locally advanced or metastatic urothelial carcinoma, regardless of PD-L1 expression.
People in a cohort of the study whose disease had progressed during or following previous treatment with a Platinum-based chemotherapy regimen, or who had disease progression within 12 months of treatment with a Platinum-based neoadjuvant or adjuvant chemotherapy regimen ( n=310 ) received a 1200-mg intravenous dose of Atezolizumab on day one of 21-day cycles until unacceptable toxicity or either radiographic or clinical progression.
The primary endpoint of the study was objective response rate ( ORR ) as assessed by an independent review facility ( IRF ) using Response Evaluation Criteria in Solid Tumors ( RECIST ) v1.1.
Secondary endpoints included duration of response ( DOR ).
The median follow-up time for this cohort was 14.4 months
The ORR was 26% for the subgroup with the highest positivity for PD-L1, 18% for the subgroup with lower positivity, and 15% for all patients.
Complete responses were seen in up to 11% of patients in the highest-positivity subgroup and in 5% of all patients. The median duration of response ( range, 2.1, 13.8+ months ) was not reached in the cohort as a whole or in the high-positivity group ( 4.2, 13.8+ ). For those in the lower-positivity group, the median duration of response was of 12.7 months.
Median progression-free survival was 2.1 months for all patients. At 6 months, it was 30% in the highest-positivity subgroup, 17% in the lower-positivity subgroup, and 21% in the subgroup with no/minimal PD-L1 expression.
Median overall survival was 7.9 months for all patients, 11.4 months for the highest-positivity subgroup, and 6.7 months for the lowest-positivity subgroup. Twelve-month overall survival was 36% for all patients, 48% for the high group, and 30% for the low group.
In a subset of people in the IMvigor 210 study with disease progression following neoadjuvant or adjuvant Platinum-containing therapy ( n=59 ), Atezolizumab shrank tumors ( ORR ) in 22.0% ( 95% CI: 12.3, 34.7 ) of people.
The most common grade 3-4 adverse reactions ( greater than or equal to 2% ) were: urinary tract infection ( 9% ), anemia ( 8% ), fatigue ( 6% ), dehydration, intestinal obstruction ( partial or complete blockage of the bowel ), urinary obstruction, hematuria ( 3% ), dyspnea ( 4% ), acute kidney injury, abdominal pain ( 4% ), venous thromboembolism, sepsis and pneumonia.
Three people ( 0.9% ) experienced either sepsis, pneumonitis or intestinal obstruction, which led to death.
Atezolizumab was discontinued for adverse reactions in 3.2% ( n=10 ) of the 310 patients.
Metastatic urothelial cancer is associated with a poor prognosis and limited treatment options. It is a disease that has seen no major advances for more than 30 years.
Urothelial cancer is the ninth most common cancer worldwide, with 430,000 new cases diagnosed in 2012, and it results in approximately 145,000 deaths globally each year.
Men are three times more likely to suffer from urothelial cancer, compared with women, and the disease is three times more common in developed countries than in less developed countries.
Atezolizumab is a monoclonal antibody designed to bind with a protein called PD-L1. Atezolizumab is designed to directly bind to PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Atezolizumab may enable the activation of T cells. Atezolizumab may also affect normal cells. ( Xagena )
Source: Roche, 2016