4157 - A phase II study investigating the safety and efficacy of neoadjuvent atezolizumab in muscle invasive bladder cancer (ABACUS)

Background

Atezolizumab is a PD-L1 inhibitor, which is licenced in metastatic urothelial cancer. This study investigates the efficacy and safety of neoadjuvant atezolizumab given prior to cystectomy in operable muscle invasive transitional cell carcinoma of the bladder.

Methods

This single arm phase 2 study investigated 2 cycles of atezolizumab (1200mg Q3) prior to cystectomy in muscle invasive transitional cell cancer (T2-4N0M0). Pathological complete response (pCR) occurring in ≥ 20% of patients was the primary endpoint. Biomarker analysis on sequential tissue was a co-primary endpoint. Cross sectional imaging was performed at baseline and prior to cystectomy which occurred 4 - 8 weeks after starting atezolizumab. Radiological response was assessed. Adverse events (AEs) and surgical complications were assessed using CTCAE v4.03 and the Clavien-Dindo classification. Updated analysis with 75 patients will be presented. IMCORE provided biomarker analysis.

Results

At baseline pT2, T3, T4 disease occurred in 73%, 20% and 7% of patients respectively. 16 (21%) patients had only 1 cycle (9 due to AEs). 7 patients did not have cystectomy (1 disease progression, 2 treatment related AE). There was 1 potential treatment related death during treatment/perioperative period (cardiovascular disease). Treatment related grade 3/4 toxicity occurred in 12% of patients. Grade 3 or 4 surgical complications occurred in 31% of pt. The pCR rate was 20/68 (29%) [95%CI: 19% to 42%] (pT0 24%, Tis 6%, T1 9% T2 24% T3 22% T4 15% stage at surgery). 39% of patients were down staged to non-muscle invasive disease. 3/20 (15%) of the pCR patients had pT3/4 disease at baseline. 47% patients were positive for PD-L1 (≥5% IC SP142); pCR rates were 38% and 27% in PD-L1 positive and negative tumours respectively (n = 62). 47 patients had sequential imaging and radiologically measurable disease at baseline. 28% [95%CI, 16% to 43%] and 17% [95%CI, 8% to 31%] of these patients radiologically responded and progressed respectively.

Conclusions

Neoadjuvant atezolizumab is safe and associated with a meaningful pathological CR rate at this interim stage. Further exploration is justified.

Clinical trial identification

NCT02662309.

Legal entity responsible for the study

Queen Mary University of London.

Funding

F. Hoffmann - La Roche Ltd.

Editorial Acknowledgement

Disclosure

I. Duran: Consulting or advisory role: roche/Genentech, MSD Oncology, Bayer, Bristol-Myers Squibb; Travel, accommodation, expenses: Roche/Genentech; Honoraria: Bristol-Myers Squibb, Ipsen, Roche/Genentech; Research funding: Roche/Genentech (institution). S.J. Crabb: Consulting or Advisory role: Roche, Clovis Oncology, Bayer, Janssen-Cilag; Travel, accommodation, expenses: Bayer, Merck, Ipsen, Bristol-Myers Squibb, Roche, Janssen-Cilag; Honoraria: Novartis, Roche, Janssen-Cilag; Research funding: AstraZeneca, Astex Pharmaceuticals, Plexxikon, Clovis Oncology. M.S. van der Heijden: Consulting or advisory role (institution): Roche/Genentech, Astellas Pharma, AstraZeneca/MedImmune, Bristol-Myers Squibb; Travel, accommodation, expenses: Novartis, Astellas Pharma, MSD Oncology; Research funding: Astellas Pharma (institution). G. Gravis: Travel, accommodation, expenses: Novartis, Sanofi, Janssen Oncology, Bristol-Myers Squibb, Astellas Pharma, Takeda. U. Anido Herranz: Consulting or advisory role: Bayer; Travel, accommodation, expenses: Astellas Pharma; Honoraria: Pfizer, Novartis, Bayer. A. Ravaud: Consulting or advisory role: Pfizer, Novartis, Bristol-Myers Squibb, Ipsen, Roche; Travel, accommodation, expenses: Pfizer, Novartis, Bristol-Myers Squibb; Honoraria: Pfizer, Bristol-Myers Squibb, Novartis; Research funding (institution): Pfizer, Novartis. C. Suarez: Consulting or advisory role: Bristol-Myers Squibb, Ipsen, Sanofi, Pfizer; Travel, accommodation, expenses: Bristol-Myers Squibb; Honoraria: Roche. A. Lorch: Consulting or advisory role: Bristol-Myers Squibb, Novartis, AstraZeneca, Roche; Travel, accommodation, expenses: Novartis, Ipsen; Honoraria: Astellas Scientific and Medical Affairs Inc, Ipsen. C.N. Sternberg: Consulting or advisory role: Bristol-Myers Squibb, Novartis, Janssen, Bayer, Eisai, MSD, Lilly, Clovis Oncology, Ferring; Honoraria: Pfizer, Astellas Pharma, Sanofi, Ipsen, AstraZeneca. T.B. Powles: Consulting or advisory role: Roche/Genentech, Bristol-Myers Squibb, Merck, Novartis, AstraZeneca; Honoraria: Roche/Genentech, Bristol-Myers Squibb, Merck; Research funding: AstraZeneca/MedImmune, Roche/Genentech; Other relationship: Ipsen, Bristol-Myers Squibb. All other authors have declared no conflicts of interest.