San Francisco, CA USA (UroToday.com) Much excitement has centered around immune checkpoint blockade over the past few years. In this session, Dr. Hoffman-Censits presented the results of a phase II trial of atezolizumab as second line therapy in platinum treated locally advanced or metastatic urothelial carcinoma (mUC).
Advanced UC is uniformly fatal after failure of platinum chemotherapy. Durable responses are not routinely observed in these patients. Grade 3-4 adverse events (AEs) are high with second line chemotherapeutic options making patients challenging to treat. The median survival in second line setting is only 9 months at best. Thus, there is a clear need for better agents after first line platinum-based therapies.
Signaling mediated by PD-L1 (expressed in mUC) can inhibit antitumor immune responses. Through inhibition of PD-L1, atezolizumab can enhance T-cell priming and reinvigorate suppressed immune cells.
The IMvigor 210 study includes patients with mUC whose tumors are PD-L1 positive and have progression during/following platinum-based first line chemotherapy. PD-L1 positivity is determined based on 3 scoring levels: IC2/3 (≥5%), IC1 (≥1 but <5), and IC0 <1%). They receive atezolizumab 1200mg IV every 3 weeks until loss of benefit. The co-primary endpoints are overall response rates (ORR) by RECIST v1.1 criteria and ORR per investigator-assessed modified RECIST criteria. Key secondary endpoint are duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
A total of 310 patients were evaluated. Median age was 66 years, 78% of patients were male, 74% had a bladder primary, and 37% had prior cystectomy. PD-L1 status was 32%, 35%, and 33% for IC2/3, IC1, and IC0, respectively. ORR for all comers was 15% (95%CI 11-19%). Though responses were seen in all PD-L1 subgroups, greater ORR was associated with higher PD-L1 IHC status. Complete responses (CR) were seen in 5% of all comers and up to 11% in patients with IC2/3. Responses were durable and the median DOR (range 2-13.7 months) was not reached in any PD-L1 subgroup at median follow-up of 11.7 months (range 0.2-15.2 months). Ongoing responses were seen in 38/45 (84%) responding patients. The disease control rate (defined as CR+partial response+stable disease) was 35%, 21%, and 19% for IC2/3, IC1, and IC0 IHC subgroups, respectively. Median PFS was 2.1 months for all patients and 6-month PFS occurred in 30%, 17%, and 21% of IC2/3, IC1, and IC0 IHC subgroups, respectively. The 12-month OS was 48%, 30%, and 36% for IC2/3, IC1, and IC0 IHC subgroups, respectively. This compares favorable with estimates of 20% 12-month OS for patients in a second line only setting (Agarwal N et al., Clin Genitourin Cancer 2014). The safety profile was acceptable with only 11% of patients reporting serious adverse events (AEs) and no deaths attributable to therapy. The AE profile was similar across IHC groups.
Dr. Hoffman-Censits concluded that the primary analysis of the IMvigor 210 phase 2 trial demonstrates that atezolizumab has the potential to change the standard of care in mUC. Ongoing trials of atezolizumab in mUC including NCT02302807 and NCT02589717 have the potential to add to our knowledge in this space.
Presented By:
Dr. Jean H. Hoffman-Censits, MD
Jefferson University
Reported By:
Benjamin T. Ristau, MD at the 2016 Genitourinary Cancers Symposium - January 7 - 9, 2016 – San Francisco, CA
Fox Chase Cancer Center, Philadelphia, PA