Barcelona, Spain-Adding immunotherapy in the form of atezolizumab (Tecentriq) to platinum-based chemotherapy extends progression-free survival (PFS) compared with chemotherapy alone in patients with previously untreated metastatic urothelial carcinoma, according to results from a phase III study.
In the IMvigor130 study, after a median follow-up of 11.8 months, median PFS was 8.2 months in patients randomized to atezolizumab plus platinum-based chemotherapy versus 6.3 months in those randomized to placebo plus platinum-based chemotherapy, corresponding to a statistically significant hazard ratio (HR) of 0.82 (p=.007).
The data were announced by Enrique Grande, MD, at the European Society of Medical Oncology annual congress in Barcelona, Spain.
“IMvigor130 is the first immune checkpoint inhibitor study to demonstrate an improvement in PFS over standard of care in first-line metastatic urothelial carcinoma,” he said. “The results… support the use of atezolizumab in combination with chemotherapy as an important new treatment option for patients with untreated metastatic urothelial carcinoma.”
Cisplatin-based chemotherapy had been the standard first-line treatment in metastatic urothelial cancer for more than 30 years. About 50% of patients with metastatic urothelial cancer, however, are ineligible for cisplatin, and they generally receive inferior carboplatin-based regimens, said Dr. Grande, head of medical oncology at MD Anderson Cancer Center, Madrid, Spain.
PD-1 and PD-L1 inhibitors are the first new systemic therapies for metastatic urothelial cancer, both indicated for first-line treatment of cisplatin-ineligible patients and for patients who experience disease progression despite platinum-based chemotherapy. IMvigor130 is the first clinical trial examining the efficacy of combining immunotherapy and chemotherapy in this field.
IMvigor130 randomized 1,213 patients with either cisplatin-eligible or cisplatin-ineligible metastatic urothelial cancer from 35 countries in a 1:1:1 ratio to atezolizumab plus platinum-based chemotherapy (arm A), atezolizumab alone (arm B), or placebo plus platinum-based chemotherapy (arm C). The co-primary efficacy endpoints were investigator-assessed PFS and overall survival (OS) in arm A versus arm C, and OS in arm B versus arm C.
As part of the chemotherapy regimen, gemcitabine was administered at 1,000 mg/m2 IV on days 1 and 8, together with physician’s choice of either carboplatin, AUC 4.5 IV, or cisplatin, 70 mg/m2 IV on day 1. Atezolizumab was dosed at 1,200 mg IV on day 1 of each 3-week treatment cycle. Tumors were assessed at baseline and every 9 weeks until disease progression or other events.
About two-thirds of patients in all three arms had PD-L1 expression on immune cells, and about one-fourth in each arm had high PD-L1 immune cell expression (IC2/3). Cisplatin ineligibility was 45% in arm A, 30% in arm B, and 35% in arm C. Carboplatin was the investigator choice of chemotherapy in 70%, 63%, and 66%, respectively.