Abstract 687P
Background
The NIVOREN GETUG-AFU 26 study reported safety and efficacy of nivolumab in patients (pts) with RCC in a “real-world setting”. A translational research program was launched to quantify baseline cytokine levels and correlate them with outcomes to nivolumab.
Methods
Patients treated with nivolumab at a single institution (Institute Gustave Roussy) as part of the phase II NIVOREN GETUG-AFU 26 were included in this discovery cohort. A panel of 14 different plasma cytokines and proteins (VEGF, VCAM-1, IL-6, IL-7, IL-8, IL-10, APRIL, BAFF, 4-1BB, BCA, SDF-1, MDC, IFNy and TNF-alpha) were quantified for each baseline plasma sample using the Elisa-based Meso Scale Discovery electrochemiluminescence assay. The association between cytokine levels and objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) was evaluated.
Results
Overall, 40 pts were included for cytokine analysis in this discovery cohort. Baseline characteristics were similar to the overall trial population, except that they had a greater number of good-prognostic pts. The IMDC risk score breakdown was 40% good, 42.5% intermediate and 17.5% poor. With a median follow-up of 20.4 months, mOS data was immature at data cut-off. Overall survival was 82.4% at 12 months. Increased levels of IL-6, BCA and BAFF were significantly negatively associated with survival (IL-6: HR=4.41, 95%CI: 1.26-15.43, p=0.0112; BCA: HR=4.74, 95%CI: 1.35-16.64, p=0.0076, and BAFF: HR=4.39, 95%CI:1.26-15.32, p=0.0114). Increased levels of VCAM and IL-10 seemed associated with worse survival outcomes, however without reaching statistical significancy. No associations with PFS or ORR were seen. Table: 687P
| Cut-off | HR (95%CI) | P-value | |
| IL-6 | Percentile 75 | 4.41 (1.26-15.43) | 0.0112 |
| BCA | Percentile 75 | 4.74 (1.35-16.64) | 0.0076 |
| BAFF | Percentile 75 | 4.39 (1.26-15.32) | 0.0114 |
| VCAM | Percentile 75 | 3.16 (0.84-11.84) | 0.0714 |
| IL-10 | Percentile 50 | 3.24 (0.83-12.61) | 0.0723 |
Conclusions
Higher baseline plasma levels of IL-6, BCA and BAFF were significantly associated with worse survival outcomes in mRCC pts treated with nivolumab within an exploratory cohort of NIVOREN trial. Validation studies are ongoing.
Clinical trial identification
NCT03013335.
Editorial acknowledgement
Legal entity responsible for the study
Unicancer.
Funding
Institut National du Cancer and Bristol-Myers Squibb.
Disclosure
N. Rioux-Leclercq: Financial Interests, Personal and Institutional, Other, Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: BMS; Financial Interests, Personal and Institutional, Other, Honoraria (self), Advisory / Consultancy: Janssen-Cilag; Honoraria (self), Advisory / Consultancy: Ipsen. Y. Vano: Financial Interests, Personal, Other, Honoraria (self), Advisory / Consultancy, Travel / Accommodation: Ipsen; Financial Interests, Personal, Other, Honoraria (self), Advisory / Consultancy: Pfizer; Travel / Accommodation / Expenses: MSD; Financial Interests, Personal, Other, Honoraria (self), Travel/Accommodation/Expenses: BMS; Financial Interests, Personal, Other, Honoraria: Astellas; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Other, Honoraria (self), Advisory / Consultancy: Janssen-Cilag; Honoraria (self), Advisory / Consultancy: SANOFI; Financial Interests, Personal, Other, Honoraria (self), Travel/Accommodation/Expenses: Roche. B. Beuselinck: Financial Interests, Personal and Institutional, Other, Advisory / Consultancy, Research grant / Funding: BMS. B. Escudier: Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal and Institutional, Research Grant: AVEO; Financial Interests, Personal, Other, personal fees: BMS; Financial Interests, Personal, Other, personal fees: AVEO; Financial Interests, Personal, Other, personal fees: Ipsen; Financial Interests, Personal, Other, personal fees: Pfizer; Financial Interests, Personal, Other, personal fees: Oncorena; Financial Interests, Personal, Other, personal fees: Immunicum; Financial Interests, Personal, Other, personal fees: Novartis; Financial Interests, Personal, Other, personal fees: Roche. L. Albiges: Financial Interests, Personal and Institutional, Other, grants/Honoraria: Pfizer; Financial Interests, Personal and Institutional, Other, grants/honoraria: NOVARTIS; Financial Interests, Personal and Institutional, Other, grants/honoraria: BMS; Financial Interests, Personal and Institutional, Other, grants/honoraria: Ipsen; Financial Interests, Personal and Institutional, Other, grants/honoraria: Roche; Financial Interests, Personal and Institutional, Other, grants/honoraria: AstraZeneca; Financial Interests, Personal and Institutional, Other, grants/honoraria: Amgen; Financial Interests, Personal and Institutional, Other, grants/honoraria: Astellas; Financial Interests, Personal and Institutional, Other, grants/honoraria: Exelixis; Financial Interests, Personal and Institutional, Other, grants/honoraria: Corvus Pharmaceuticals; Financial Interests, Personal and Institutional, Other, grants/honoraria: Peloton Therapeutics; Financial Interests, Personal and Institutional, Other, grants/honoraria: MSD; Financial Interests, Personal and Institutional, Other, grants/honoraria: Merck. N. Chaput: Financial Interests, Personal and Institutional, Sponsor/Funding. AstraZeneca; Financial Interests, Personal and Institutional, Sponsor/Funding. BMS; Financial Interests, Personal and Institutional, Sponsor/Funding. GSK; Financial Interests, Personal and Institutional, Sponsor/Funding. Roche; Financial Interests, Personal and Institutional, Sponsor/Funding. Sanofi; Financial Interests, Personal and Institutional, Sponsor/Funding. Cytune Pharma. All other authors have declared no conflicts of interest.