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Adding immunotherapy in the form of atezolizumab (Tecentriq) to platinum-based chemotherapy extends progression-free survival compared with chemotherapy alone in patients with previously untreated metastatic urothelial carcinoma, according to results from a phase III study.
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.
Next: Atezolizumab plus chemo PFS benefit seen in all subgroupsAtezolizumab plus chemo PFS benefit seen in all subgroups
The PFS advantage to atezolizumab plus chemotherapy versus chemotherapy alone was evident in all subgroups analyzed.
“Those patients overexpressing PD-L1, and especially those patients receiving cisplatin as a platinum-based chemotherapy, seemed to do better [with the addition of atezolizumab], but this is an exploratory analysis and just hypothesis-generating,” said Dr. Grande.
In an interim analysis, median OS was 16.0 months in arm A versus 13.4 months in arm C (HR: 0.83, p=.027), a difference that “was remarkable in that there were 20% of patients in the chemotherapy arm that crossed over after progression to receive an immuno-oncology agent,” he said. As with PFS, the OS advantage with atezolizumab added to chemotherapy appeared to be greatest in patients with the highest expression of PD-L1 (IC2/3), especially when combined with cisplatin.
Median OS was 15.7 versus 13.1 months in arms B and C, respectively (HR: 1.02, 95% CI: 0.83–1.24). However, median OS in the patients with high expression of PD-L1 was 17.8 months in arm B and 13.1 months in arm C, for an HR of 0.68 (95% CI: 0.43-1.08) in favor of atezolizumab monotherapy versus placebo/chemotherapy.
Objective response rates were 47% with atezolizumab plus chemotherapy, 23% with atezolizumab monotherapy, and 44% with chemotherapy alone. Complete responses were about twice as likely with the combination compared with chemotherapy or immunotherapy alone-13%, 7%, and 6%, respectively. Median duration of response was 8.5 months in the combination arm, 7.6 months in the standard chemotherapy arm, and was not reached in the atezolizumab-only arm.
Adverse events leading to treatment withdrawal occurred in 34%, 6%, and 34% of patients in arms A, B, and C, respectively.
Roche provided funding for the study. Dr. Grande has served on the speakers’ bureau and provided expert testimony for and received a research grant/funding from Roche. For full disclosures, see bit.ly/LBA14PRdisclosures.