Institut Paoli-Calmettes, Marseille, France
Emilien Billon , Cécile Dalban , Stephane Oudard , Christine Chevreau , Brigitte Laguerre , Philippe Barthélémy , Delphine Borchiellini , Lionnel Geoffrois , Sylvie Negrier , Florence Joly , Antoine Thiery-Vuillemin , Marine Gross-Goupil , Frederic Rolland , Frank Priou , Hakim Mahammedi , Florence Tantot , Bernard Escudier , Sylvie Chabaud , Laurence Albiges , Gwenaelle Gravis
Background: Glandular metastases (GMs) (adrenal, pancreas, thyroid, ovary, breast, or prostate) are rare in mccRCC. Several studies have observed significantly longer overall survival (OS) for GM patients treated with anti-angiogenic therapy. This study assesses outcomes from mccRCC treated with nivolumab with or without GMs. Methods: The GETUG-AFU 26 NIVOREN, phase II trial assessed the activity and safety of nivolumab in pts with mccRCC who failed antiangiogenic therapies (NCT03013335). Pts were stratified in two subgroups according to the presence of at least one GM. Specific analyzes were performed for pancreatic and adrenal metastases. Primary endpoint was OS, secondary endpoint were progression free survival (PFS) and overall response rate (ORR). Results: Between February 2016 and July 2017, among 720 patients treated by nivolumab 217 patients had GM (151: adrenal and 86: pancreatic metastases). Clinical characteristics were comparable between the two subgroups except for IMDC poor subgroup (19% vs 28%) and for Furhman grade IV (13.5% vs 23.4%) for GM and non GM respectively. Median time between metastatic disease and nivolumab was 3.2 years (y) vs 2 y for GM and non GM respectively and 2.8 vs 2.1 y with or without adrenal metastasis. There was no statistical difference in outcomes between pts with or without GMs. However, pts with adrenal metastases had worse OS (12-months survival: 64% vs 71.1%; HR 1.51 (1.19-1.92)); shorter PFS (6-months survival: 27.2% vs 36.6%; HR 1.29 (1.07-1.57)) and lower ORR (12.5% [7.6%; 19.0%] vs 23.2% [19.8%; 27.0%]; p = 0.005) than non-adrenal metastases. Conversely, patients with pancreatic metastases had significantly longer overall survival (12-months survival: 82.3% vs 67.9%; HR 0.59 (0.40-0.85)) in univariate analysis compared to non-pancreatic metastases. In multivariate analysis, only adrenal metastasis remained associated with dismal prognosis (Table). Conclusions: Adrenal metastasis is an independent poor prognostic factor for response and survival in the GETUG-AFU 26 NIVOREN phase II trial. Limited activity with nivolumab is observed for patients with adrenal metastases from mccRCC without difference with previous anti angiogenic therapy. Molecular characterization could help to identify the angiogenic profile of adrenal metastases. Clinical trial information: NCT03013335.
Factor Label | Events/N (Multivariate) | Hazard Ratio (95% CI) (Multivariate) | P-value |
---|---|---|---|
Adrenal metastasis | <.0001 | ||
Yes (vs no) | 91/150 | 1.65 (1.29-2.10) | |
Sex | 0.6757 | ||
Female (vs male) | 75/159 | 0.95 (0.73-1.23) | |
Age | 0.0011 | ||
≥ 70 y/o (vs < 70y/o) | 112/202 | 1.46 (1.16-1.84) | |
IMDC prognostic | <.0001 | ||
Intermediate (vs Favorable) | 186/399 | 2.07 (1.45-2.97) | |
Poor (vs Favorable) | 121/179 | 4.54 (3.11-6.61) |
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