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Adding Atezolizumab to Front-Line Platinum-Based Chemotherapy Improves Progression-Free Survival in mUC

Atezolizumab administered with chemotherapy was well-tolerated in patients with metastatic urothelial cancer
30 Sep 2019
Genitourinary cancers;  Cancer Immunology and Immunotherapy;  Anticancer agents & Biologic therapy

Patients with locally advanced or metastatic urothelial carcinoma (mUC) demonstrated prolonged progression-free survival (PFS) with the addition of atezolizumab to first-line platinum-based chemotherapy, as compared with chemotherapy alone according to phase III data from the IMvigor130 study that were presented at the ESMO Congress 2019 in Barcelona, Spain.

In patients with mUC first-line treatment may be platinum-based chemotherapy or checkpoint inhibitors, depending on patient eligibility and PD-L1 status.

Therefore, Enrique Grande, Head of the Medical Oncology Department, MD Anderson Cancer Centre in Madrid, Spain and colleagues investigated the efficacy of atezolizumab plus platinum-based chemotherapy, compared to atezolizumab monotherapy or platinum-based chemotherapy alone in the phase III, global, multicentre, randomised, partially blinded IMvigor130 study (NCT02807636).

IMvigor130 enrolled 1213 patients who had not received prior systemic therapy for mUC and were elegible for platinum-based chemotherapy. The patients were randomised to receive: Atezolizumab plus platinum-based chemotherapy comprised of gemcitabine plus either cisplatin or carboplatin (arm A; n = 447), atezolizumab monotherapy (arm B; n = 369), or platinum-based chemotherapy plus placebo as the control (arm C; n=397). Gemcitabine at 1000 mg/m2 was administered on days 1 and 8 by i.v., carboplatin at AUC 4.5 or cisplatin at 70 mg/m2 were given by i.v. on day 1 and atezolizumab at 1200 mg was given by i.v. on day 1 of each 3-week cycle, either as monotherapy or with placebo.

Tumour assessment was done at baseline and every 9 weeks until investigator-assessed disease progression (PD) by RECIST v1.1 or other events occurred.

The co-primary efficacy endpoints were investigator-assessed PFS per RECIST v1.1. and overall survival (OS) in arm A (atezolizumab plus chemotherapy) versus arm C (platinum-based chemotherapy) and OS in arm B (atezolizumab monotherapy) versus arm C.

Progression-free survival was longer with the atezolizumab combination treatment

At the interim analysis the study met the co-primary endpoint of investigator-assessed PFS; after a median follow-up of 11.8 months, in arm A the combination of atezolizumab plus platinum-based chemotherapy prolonged median PFS to 8.2 months (95% confidence interval [CI], 6.5-8.3) compared to 6.3 months (95% CI, 6.2, 7.0) with placebo/platinum-based chemotherapy in arm C (hazard ratio  [HR] 0.82; 95% CI, 0.70, 0.96; p = 0.007).

Grande ESMO 2019 News

IMVIGOR130 met the primary endpoint of prolonging progression-free survival of the combination of atezolizumab plus chemotherapy versus chemotherapy alone in first-line treatment of metastatic urothelial carcinoma patients.

© Enrique Grande.

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 OS results observed at the interim analysis were encouraging but not statistically significant; the OS comparison did not cross the prespecified interim efficacy boundary and median OS was 16.0 months in arm A versus 13.4 months in arm C (HR 0.83; 95% CI, 0.69-1.00; p = 0.027) favouring the combination arm.

Regarding the comparison of atezolizumab monotherapy with control chemotherapy in the intent-to-treat (ITT) population, the median OS in arm B was 15.7 months versus and 13.1 months in arm C (HR 1.02; 95% CI, 0.83-1.24).

Patients with PD-L1 expression showed a promising trend to improved survival vs platinum-based chemotherapy

In the comparison of atezolizumab monotherapy (arm B) versus chemotherapy (arm C) in patients with immune cell PD-L1 expression (IC2/3), median OS was not estimable compared to 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 (AEs) leading to treatment withdrawal occurred in 34%, 6% and 34% of patients in arms A, B and C, respectively.

Discussant points

Thomas Powles of the Barts Cancer Centre, London, UK who discussed how do the results of Imvigor130 change things in bladder cancer questioned why has it take so long to have a positive front-line randomised trial in urothelial cancer. He said that it is probably needed to wait for overall survival data before changing the clinical practice.

Conclusions

The authors concluded that the addition of atezolizumab to platinum-based chemotherapy in the first-line treatment of patients with mUC improved PFS over platinum-based chemotherapy alone. The combination safety profile was consistent with that observed for the individual agents.

Disclosure

This study was funded by F. Hoffmann-La Roche, Ltd.

Reference

LBA14_PR –Grande E,Galsky M, Arranz Arija JA, et al. IMvigor130: efficacy and safety from a Phase 3 study of atezolizumab (atezo) as monotherapy or combined with platinum-based chemotherapy (PBC) vs placebo + PBC in previously untreated locally advanced or metastatic urothelial carcinoma (mUC).

Last update: 30 Sep 2019

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