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.
Resources from the same session
2053 - Pre-operative ipilimumab and nivolumab in locoregionally advanced, stage III, urothelial cancer (NABUCCO)
Presenter: Michiel Van der Heijden
Session: Poster Discussion – Genitourinary tumours, non-prostate
Resources:
Abstract
905PD - Multiple-cohort analysis investigating FGFR3 alteration as a predictor of non-response to neoadjuvant pembrolizumab (pembro) in muscle-invasive bladder cancer (MIBC)
Presenter: Andrea Necchi
Session: Poster Discussion – Genitourinary tumours, non-prostate
Resources:
Abstract
Slides
4138 - ADAPTeR: A phase II study of anti-PD1 (nivolumab) therapy as pre- and post-operative therapy in metastatic renal cell carcinoma.
Presenter: Lewis Au
Session: Poster Discussion – Genitourinary tumours, non-prostate
Resources:
Abstract
4174 - Primary renal tumour shrinkage in patients (pts) who did not undergo upfront cytoreductive nephrectomy (uCN): subgroup analysis from the phase 3 JAVELIN Renal 101 trial of first-line avelumab + axitinib (A + Ax) vs sunitinib (S) for advanced renal cell carcinoma (aRCC)
Presenter: Laurence Albiges
Session: Poster Discussion – Genitourinary tumours, non-prostate
Resources:
Abstract
4707 - NIVOREN GETUG-AFU 26 translational study:CD8 infiltration and PD-L1 expression are associated with outcome in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC) treated with nivolumab (N).
Presenter: Yann Vano
Session: Poster Discussion – Genitourinary tumours, non-prostate
Resources:
Abstract
4823 - Efficacy and biomarker analysis of patients (pts) with advanced renal cell carcinoma (aRCC) with sarcomatoid histology (sRCC): subgroup analysis from the phase 3 JAVELIN Renal 101 trial of first-line avelumab plus axitinib (A + Ax) vs sunitinib (S)
Presenter: Toni Choueiri
Session: Poster Discussion – Genitourinary tumours, non-prostate
Resources:
Abstract
3170 - A First-in-Human Phase 1/2 Trial of the Oral HIF-2a Inhibitor PT2977 in Patients with Advanced RCC
Presenter: Eric Jonasch
Session: Poster Discussion – Genitourinary tumours, non-prostate
Resources:
Abstract
3527 - Results of the Phase 2 TRAXAR Study: A Randomized Phase 2 Trial of Axitinib and TRC105 (TRAX) versus AXitinib (AX) Alone in Patients with Advanced or Metastatic Renal Cell Carcinoma (mRCC)
Presenter: Toni Choueiri
Session: Poster Discussion – Genitourinary tumours, non-prostate
Resources:
Abstract
3113 - APACHE: an open label, randomized, phase 2 study of Durvalumab (Durva), alone or in combination with Tremelimumab (Treme), in patients (pts) with refractory germ cell tumors (GCT): results from the expanded combination therapy cohort
Presenter: Elena Farè
Session: Poster Discussion – Genitourinary tumours, non-prostate
Resources:
Abstract
4447 - Prognostic factors in metastatic seminomatous germ cell tumors and elevated human chorionic gonadotrophin (HCG) – a study of the G3
Presenter: Christoph Seidel
Session: Poster Discussion – Genitourinary tumours, non-prostate
Resources:
Abstract