Clinicaltrials.gov identifier:
Sponsor:
Hoffmann-La Roche
Enrollment:
1213
Study Design:
IMvigor130 is an international phase III trial for pts with locally advanced or mUC who had not received prior systemic therapy. Pts had an ECOG PS ≤2 and were eligible for platinum-based therapy in the 1st line setting. Pts were stratified by PD-L1 IC status (IC0 vs IC1 vs IC2/3), Bajorin risk factor score including KPS <80% versus ≥80%, the presence of visceral metastases and investigator’s choice of chemotherapy. Pts were randomized 1:1:1 to receive atezo and platinum-based therapy (cisplatin or carboplatin) plus gemcitabine (arm A; n = 451), atezo monotherapy (arm B; n = 362), or placebo plus platinum-based therapy and gemcitabine (arm C; n = 400).
Rationale:
Cisplatin-based chemotherapy has been standard first (1st) line treatment in mUC for > 30 years. Approximately 50% of patients (pts) with mUC are ineligible for cisplatin, and they generally receive inferior carboplatin-based regimens. PD-L1 and PD-1 inhibitors are the 1st new systemic therapies for mUC, both for 1st line treatment of cisplatin-ineligible pts and for pts experiencing disease progression despite platinum-based chemotherapy. The final PFS and interim OS results for IMvigor130, assessing atezolizumab (atezo) alone or in combination with gemcitabine and carboplatin or gemcitabine and cisplatin in 1st line mUC were presented.
Endpoints:
The co-primary endpoints were investigator-assessed PFS and OS in arm A vs. arm C, and OS in arm B vs. arm C using a hierarchical approach. Key secondary endpoints included investigator-assessed overall response rate (ORR), duration of response, PFS and OS in arm B vs. arm C in the PD-L1 IC2/3 subgroup, and safety.
Comments:
Whether the addition of immunotherapy to chemotherapy can improve outcomes in pts with mUC is an important question. IMvigor130 is the first trial to evaluate the combination of immunotherapy and chemotherapy in pts with mUC who are eligible and ineligible for chemotherapy. This trial represents the first positive signal in terms of PFS and a trend in OS. The results from IMvigor130 support atezo + platinum plus gemcitabine as an important new treatment option for patients with untreated mUC. Other similar trials are ongoing with other immunotherapeutic check point inhibitors.
Results:
In the intent-to-treat population, the median OS with atezo and platinum plus gemcitabine was 16 months versus and 13.4 months for chemotherapy and placebo (HR, 0.83 (95% CI, 0.69, 1.00). When stratified by PD-L1 expression, pts with PD-L1–positive tumors (IC2/3) had an improvement in OS when treated with single-agent atezo compared with chemotherapy and placebo (HR, 0.68; 95% CI, 0.43-1.08). Median OS with the PD-L1 inhibitor was not estimated and was 17.8 mos. with chemotherapy. Follow-up of OS will be continued.
