Patients with locally advanced or metastatic urothelial carcinoma demonstrated prolonged progression-free survival with the addition of atezolizumab to first-line platinum-based chemotherapy vs treatment with chemotherapy alone, according to phase III data from the IMvigor130 study presented by Grande et al at the European Society for Medical Oncology (ESMO) Congress 2019 (Abstract LBA14).
In patients with metastatic urothelial carcinoma, first-line treatment may be platinum-based chemotherapy or checkpoint inhibition, depending on patient eligibility and programmed cell death ligand 1 (PD-L1) status. Enrique Grande, MD, PhD, of MD Anderson Cancer Center in Madrid, and colleagues investigated the efficacy of atezolizumab plus platinum-based chemotherapy vs atezolizumab monotherapy or platinum-based chemotherapy alone in the phase III, global, multicenter, randomized, partially blinded IMvigor130 study.
Methods
IMvigor130 enrolled 1,213 patients who had not received prior systemic therapy for metastatic urothelial carcinoma and were eligible for platinum-based chemotherapy. The patients were randomly assigned to receive either:
- Atezolizumab plus platinum-based chemotherapy composed of gemcitabine plus either cisplatin or carboplatin (arm A; n = 447)
- Atezolizumab monotherapy (arm B; n = 369)
- Platinum-based chemotherapy plus placebo (arm C; n = 397).
Gemcitabine at 1,000 mg/m2 was administered intravenously on days 1 and 8; carboplatin at AUC 4.5 or cisplatin at 70 mg/m2 were administered intravenously on day 1; and atezolizumab at 1,200 mg was administered intravenously on day 1 of each 3-week cycle, either as monotherapy or with placebo. Tumor assessment was done at baseline and every 9 weeks until investigator-assessed disease progression by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or other events occurred.
The co-primary efficacy endpoints were investigator-assessed progression-free survival per RECIST v1.1. and overall survival in arm A (atezolizumab plus chemotherapy) vs arm C (platinum-based chemotherapy) and overall survival in arm B (atezolizumab monotherapy) vs arm C.
Results
At the interim analysis, the study met the co-primary endpoint of investigator-assessed progression-free survival; after a median follow-up of 11.8 months, in arm A, the combination of atezolizumab plus platinum-based chemotherapy prolonged median progression-free survival to 8.2 months (95% confidence interval [CI] = 6.5–8.3) vs 6.3 months (95% CI = 6.2–7.0) with placebo plus platinum-based chemotherapy in arm C (hazard ratio [HR] = 0.82, 95% CI = 0.70–0.96; P = .007).
The objective response rates were 47% in arm A, 23% in arm B, and 44% in arm C. The rates of complete response were 13%, 6%, and 7%, respectively.
The overall survival results observed at the interim analysis were encouraging but not statistically significant; the overall survival comparison did not cross the prespecified interim efficacy boundary, and median overall survival was 16.0 months in arm A vs 13.4 months in arm C (HR = 0.83, 95% CI = 0.69–1.00; P = .027), favoring the combination arm.
KEY POINTS
- The combination of atezolizumab plus platinum-based chemotherapy prolonged median PFS to 8.2 months vs 6.3 months with placebo plus platinum-based chemotherapy.
- Safety in the atezolizumab plus chemotherapy arm appeared to be consistent with the known safety profiles of the individual agents, and no new safety signals were identified with the combination.
When comparing atezolizumab monotherapy with control chemotherapy in the intent-to-treat population, the median overall survival in arm B was 15.7 months vs 13.1 months in arm C (HR = 1.02, 95% CI = 0.83–1.24).
When atezolizumab monotherapy (arm B) was compared to chemotherapy (arm C) in patients with immune cell PD-L1 expression, median overall survival was not estimable vs 17.8 months, respectively (HR = 0.68, 95% CI = 0.43–1.08).
Safety in the atezolizumab-plus-chemotherapy arm appeared to be consistent with the known safety profiles of the individual agents, and no new safety signals were identified with the combination. Adverse events leading to treatment withdrawal occurred in 34%, 6% and 34% of patients in arms A, B and C, respectively.
The authors concluded that the addition of atezolizumab to platinum-based chemotherapy in the first-line treatment of patients with metastatic urothelial carcinoma improved progression-free survival over platinum-based chemotherapy alone. The combination safety profile was consistent with that observed for the individual agents.
Disclosure: IMvigor130 was funded by F. Hoffmann-La Roche, Ltd. For full disclosures of the study authors, visit esmo.org.
