Neoadjuvant atezolizumab plus chemo effective in MIBC

Adding the PD-L1 inhibitor atezolizumab (Tecentriq) to standard neoadjuvant therapy with gemcitabine and cisplatin (GC) showed promising efficacy in patients with muscle-invasive bladder cancer (MIBC), according to data from a phase 2 trial presented at the 2021 ASCO Annual Meeting.1

The triplet regimen met the primary end point of the study by inducing a pathologic response in 69% of patients. Nearly half (44%) of patients had a pathologic complete response.

Explaining the background of the study, lead study author Samuel A. Funt, MD, a medical oncology at Memorial Sloan Kettering Cancer Center, said, “Neoadjuvant cisplatin-based chemotherapy prior to radical cystectomy (RC) improves survival for patients with MIBC. Patients who receive this therapy and are downstaged to having no residual muscle-invasive disease and negative lymph nodes at the time of surgery experience improved survival.”

Funt noted, however, that only about one-third to half of patients will achieve this result, and thus options are needed to improve upon the standard neoadjuvant chemotherapy regimen.

The study enrolled patients with cT2 to T4aN0M0 node-negative MIBC who were eligible for RC. Overall, there were 39 evaluable patients enrolled across 5 institutions.

The median patient age was 65 years (range, 58-69), 85% were male, and 64% were current or former smokers. Only 2 patients had prior BCG. The ECOG performance status was 0 for 59% of patients and 1 for 41% of patients. The PD-L1 immune cells score was IC2/3 (≥5%) for 10% (n = 4) of patients and IC0/1 (<5%) for 90% of patients.

Regarding histology, 77% of patients had pure urothelial carcinoma, not otherwise specified; 20% had urothelial carcinoma with squamous differentiation; and 3% had urothelial carcinoma with micropapillary features. The clinical T stage at presentation was T2N0 for 79% of patients, T3N0 for 18% of patients, and T4aN0 for 3% of patients.

Patients were treated with a single lead-in dose of atezolizumab and 2 weeks later started concurrent GC and atezolizumab over four 21-days cycles followed by RC. Patients could also be treated with 1 final dose of atezolizumab 3 weeks after receiving their last dose of atezolizumab while awaiting RC.

Twenty-seven (69%) patients achieved a pathologic response, defined as pathologic downstaging to non-MIBC (<pT2N0) at RC. Fourteen of the 27 patients reached <pT2N0 in first stage and 13 reached pT2N0in second stage. Seventeen (44%) of the patients were complete responders, defined as downstaging to pT0N0.

“Of the 36 patients that underwent RC-PLND, no patient with <pT2N0 has relapsed at a median follow-up of 12 months (range, 9.5-18),” said Funt.

PD-L1 was not predictive of achieving a pathologic response. All 4 PD-L1–positive patients achieved pathologic downstaging to pT2N0. Among the PD-L1–negative subgroup, 68% reached <pT2N0.

The median time from the final dose of chemotherapy to RC was 7.8 weeks (range, 5.1-17). Thirty-six (92%) of the 39 evaluable patients received all 4 planned cycles of GC.

Regarding safety, Funt said, “Treatment was associated with manageable adverse events (AEs), which did not compromise surgical resection.”

The most frequently occurring grade 3/4 AEs were neutropenia (36%), lymphopenia (16%), and anemia (11%). All were related to GC chemotherapy. There were no new safety signals regarding grade 3/4 immune-related AEs as compared with those reported in prior studies of atezolizumab. Two patients were treated with high-dose steroids for immune-related AEs.

Regarding next steps with this research, Funt said, “Additional interrogation of the genomic and host immune factors mediating response and resistance to GC plus atezolizumab is ongoing.”

Reference

1. Funt SA, Lattanzi M, Whiting K, et al. Neoadjuvant atezolizumab (A) with gemcitabine and cisplatin (GC) in patients (pts) with muscle-invasive bladder cancer (MIBC): A multicenter, single-arm, phase 2 trial. J Clin Oncol 39, 2021 (suppl 15; abstr 4517). doi: 10.1200/JCO.2021.39.15_suppl.4517