Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Lunch & Poster Display session

31P - Development of a biomarker-based calculator to predict the probability to achieve a pathologic complete response after neoadjuvant pembrolizumab in muscle-invasive bladder cancer

Date

12 Dec 2019

Session

Lunch & Poster Display session

Presenters

Laura Marandino

Citation

Annals of Oncology (2019) 30 (suppl_11): xi1-xi11. 10.1093/annonc/mdz447

Authors

L. Marandino1, M. Bandini2, R. Madison3, D. Raggi4, A. Gallina2, M. Colecchia5, R. Lucianò6, P. Giannatempo4, E. Farè4, F. Pederzoli7, M. Bianchi8, R. Colombo7, U. Capitanio7, S.M. Ali3, J.H. Chung3, J. Ross3, A. Salonia7, A. Briganti7, F. Montorsi2, A. Necchi4

Author affiliations

  • 1 Medical Oncology Dept., Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 2 Division Of Oncology/unit Of Urology, Vita Salute San Raffaele University and Urological Research Institute, 20132 - Milan/IT
  • 3 Clinical Bioinformatics Operations, Foundation Medicine, Inc, 02141 - Cambridge/US
  • 4 Medical Oncology, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, 20133 - Milan/IT
  • 5 Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 6 Pathology, Vita Salute San Raffaele University and Urological Research Institute, 20132 - Milan/IT
  • 7 Unit Of Urology, Vita Salute San Raffaele University and Urological Research Institute, 20132 - Milan/IT
  • 8 Genetics And Cell Biology, Vita Salute San Raffaele University and Urological Research Institute, 20132 - Milan/IT
More

Resources

Abstract 31P

Background

The PURE01 study (NCT02736266) evaluates preoperative pembrolizumab before radical cystectomy (RC). Here, the possibility to predict the pathologic complete response (pT0) after neoadjuvant immunotherapy could have paradigm-shifting implications for the management of patients with MIBC.

Methods

The reported analyses include comprehensive genomic profiling with FoundationONE CDx assay and programmed cell-death-ligand-1 (PD-L1) combined positive score (CPS, Dako 22C3 antibody) on baseline TURB samples. Multivariable logistic regression analyses (MVA) evaluated clinical T-stage and biomarkers (tumor mutational burden [TMB], and CPS) in association with pT0 response. Multivariable-derived coefficients were used to develop a novel risk calculator. Decision-curve analysis was used to evaluate the net benefit of the predictive model.

Results

From 02/2017 to 06/2019, 112 patients with full biomarker data were enrolled. At MVA, only CPS showed a significant association with pT0 (p = 0.005). Increasing TMB and CPS values featured a linear association with logistic pT0 probabilities (p = 0.02 and p = 0.004). Very high TMB values, associated with a predicted probability of pT0 > = 55%, were independent from CPS contribution. The coefficients of the predictive model were used to develop a risk calculator. The c-index of the model was 0.77. At decision-curve analysis, the net-benefit of the model was higher than the “treat-all” option from more than 10% threshold probabilities.

Conclusion

We presented the first biomarker-based risk stratification tool that can be used to recommend use of neoadjuvant pembrolizumab in those patients who have equal or greater chances to achieve a pT0 status compared to the literature on neoadjuvant chemotherapy or to RC alone, depending on cisplatin eligibility.

Clinical trial identification

PURE01 study (NCT02736266).

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Merck & Co., Inc., Kenilworth, NJ, USA; Associazione Italiana per la Ricerca sul Cancro (AIRC).

Disclosure

R. Madison: Shareholder / Stockholder / Stock options, Full / Part-time employment, employee and stock owner of Foundation Medicine Inc: Foundation Medicine Inc. M. Colecchia: Speaker Bureau / Expert testimony: Roche Diagnostics. S.M. Ali: Full / Part-time employment: Foundation Medicine. J.H. Chung: Full / Part-time employment: Foundation Medicine. J. Ross: Leadership role, Research grant / Funding (institution), Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. A. Salonia: Speaker Bureau / Expert testimony: Astellas Pharma; Travel / Accommodation / Expenses: Konpharma. A. Briganti: Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy: Hanssen-Cilag; Advisory / Consultancy: OPKO Health; Advisory / Consultancy: MDxHealth; Advisory / Consultancy: Ferring; Research grant / Funding (institution): Novartis. A. Necchi: Advisory / Consultancy: Merck, Incyte, AstraZeneca, Roche, Rainier Therapeutics, Clovis Oncology, Bristol-Myers Squibb, Bayer, Basilea Pharmaceutica; Research grant / Funding (institution): AstraZeneca, Ipsen, Merck and Incyte; Spouse / Financial dependant: Bayer. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings