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Poster Discussion – Genitourinary tumours, non-prostate

4374 - Phase 3 trial of adjuvant sunitinib in patients with high-risk renal cell carcinoma: comprehensive tumor genomic and transcriptomic analyses

Date

29 Sep 2019

Session

Poster Discussion – Genitourinary tumours, non-prostate

Presenters

Alain Ravaud

Citation

Annals of Oncology (2019) 30 (suppl_5): v356-v402. 10.1093/annonc/mdz249

Authors

A. Ravaud1, J. Martini2, K. Ching3, M. Staehler4, A. Magheli5, B. Escudier6, X.J. Mu3, O. Valota7, X. Lin2, R.J. Motzer8

Author affiliations

  • 1 Oncology, CHU Bordeaux Hopital St. André, 33000 - Bordeaux/FR
  • 2 Global Product Development-oncology, Pfizer, 92121 - La Jolla/US
  • 3 Oncology Research Unit, Pfizer, 92121 - La Jolla/US
  • 4 Oncology, University of Munich, Munich/DE
  • 5 Oncology, Charité Universitaetsmedizin Berlin, Berlin/DE
  • 6 Oncology, Gustave Roussy - Cancer Campus, 94805 - Villejuif/FR
  • 7 Oncology, Pfizer S.r.L, Milan/IT
  • 8 Medicine, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US

Resources

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Abstract 4374

Background

In the S-TRAC trial, adjuvant sunitinib (SU) prolonged disease-free survival (DFS) versus placebo (PBO) in patients (pts) with loco-regional renal cell carcinoma (RCC) at high risk of recurrence after nephrectomy. We previously applied the 16-gene Recurrence Score and confirmed its prognostic value (Clin Cancer Res 2018;15:4407). Here, we report the results of retrospective exploratory genomic and transcriptomic analyses using nephrectomy biospecimens from the S-TRAC trial.

Methods

Formalin-fixed paraffin-embedded tumor tissue blocks from patients who provided informed consent were used for whole exome (WES) and whole transcriptome (RNAseq) sequencing (Personalis, Menlo Park, CA; Genome Med. 2015;7:71) to examine somatic mutations and analyze relevant gene expression signatures (GES) in relation to clinical outcome. GES analyses included published signatures [effector T-cell (Teff), angiogenesis (Angio), myeloid inflammation (Minf)] among others. Cox proportional analyses of DFS were performed for each genotype or signature in SU versus PBO groups and between genotypes or signatures within each treatment group. Estimates of related parameters were reported.

Results

In all, 171 pts (SU, n = 91; PBO, n = 80) were genotyped and 133 (SU, n = 72; PBO, n = 61) were included in the GES analyses. Differences in DFS were observed relative to wildtype when mutations in genes such as ARID1A, MTOR, or ROBO3 were present; presence or absence of mutation in BAP1, SETD2 or PBRM1, however, did not distinguish pts with respect to DFS. Low tumor mutational burden (TMB) was associated with longer DFS in PBO as compared to high TMB (hazard ratio (HR) 0.253; 95% CI: 0.119, 0.541), but not in SU. Low-Angio GES showed a modest association with shorter DFS vs high-Angio GES in PBO (HR 1.912; 95% CI: 0.829, 4.409) but did not differentiate DFS in SU. Pts with low-Minf GES in SU had longer DFS vs those with high-Minf GES (HR 0.304; 95% CI: 0.132, 0.702).

Conclusions

These findings define molecular features that differentiate SU-specific outcomes in adjuvant RCC and may inform personalized therapy strategies for pts at high risk of recurrence. Independent validation studies are needed to confirm these findings.

Clinical trial identification

NCT00375674.

Editorial acknowledgement

Vardit Dror and David Cope Engage Scientific Solutions, funded by Pfizer.

Legal entity responsible for the study

Pfizer.

Funding

Pfizer.

Disclosure

A. Ravaud: Advisory / Consultancy, Travel / Accommodation / Expenses, lecture fees: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses, lecture fees: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses, lecture fees: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses, lecture fees: Ipsen; Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Merck Sharp & Dohme. J. Martini: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. K. Ching: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. M. Staehler: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: GlaxoSmithKline; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Exelixis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche. A. Magheli: Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Astellas; Speaker Bureau / Expert testimony: Janssen. B. Escudier: Advisory / Consultancy, lecture fees: Pfizer; Advisory / Consultancy, lecture fees: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Roche. X.J. Mu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. O. Valota: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. X. Lin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. R.J. Motzer: Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Merck; Advisory / Consultancy: Incyte; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): GlaxoSmithKline.

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