Abstract 711P
Background
Metastatic urothelial carcinoma (mUC) is an aggressive disease with few available therapeutics until recent approval of immune checkpoint inhibitors (ICI), fibroblast growth factor inhibitor receptor inhibitors and antibody-drug conjugate. Nevertheless, some patients do not respond to these treatments and predictive biomarkers are needed, especially for ICI.
Methods
We retrospectively assessed data from mUC patients with a solid biopsy included in three genomic profiling clinical trials in two cancer centers: MOSCATO (NCT01566019) and MATCH-R (NCT02517892) at Gustave Roussy Institute, and BIP (NCT02534649) at Bergonié Institute.
Results
Among 240 patients, next generation sequencing was successful in 77.1% of them (n=185). The median number of prior systemic therapies was 2.0 (range: 0-8). A total of 676 genomic alterations (GA) were identified in 150 genes (501 mutations, 115 gene amplifications or gain, 46 gene deletions or loss and 14 gene rearrangements) with a median of 3 (range: 1-17) per cases. The 9 genes most often altered were: TP53 (n=94, 50.8%), FGFR3 (n=38, 20.5%), TERT (n=33, 17.8%), PIK3CA (n=27, 14.6%), CDKN2A (n=21, 11.4%), CCND1 (n=16, 8.6%), ARID1A (n=14, 7.6%), ERBB2 (n=14, 7.6%), and TSC1 (n=14, 7.6%). An actionable alteration according to molecular tumor board was found for 59.9% of patients. After applying clinical and molecular exclusion criteria, 20% were assigned to receive a targeted therapy. Among the 37 patients treated according to their GA, we observed 11 partial responses (34.4%), 12 stable diseases (37.5%) and 9 progressions (28.1%). Median progression-free survival (PFS) and overall survival (OS) were 3.2 and 6.7 months, respectively. On the 112 patients treated with ICI, median PFS was 2.4 months and median OS 9.6 months. TP53 aberrations were significantly associated with worse objective response (15.1 vs 35.6%, p=0.03), median PFS (1.7 vs 4.1 months, p<0.01) and median OS (6.5 vs 16.1 months, p<0.01) for ICI.
Conclusions
Up to 60.0% of mUC harbored at least one clinically relevant GA with potential to influence and personalize therapy.
Clinical trial identification
MOSCATO (NCT01566019), MATCH-R (NCT02517892), BIP (NCT02534649).
Editorial acknowledgement
Legal entity responsible for the study
Institut Gustave Roussy.
Funding
Has not received any funding.
Disclosure
C.J. Pobel: Financial Interests, Personal, Other, Travel accommodations: Sandoz; Financial Interests, Personal, Other, Travel accommodations: Amgen, Sandoz: Amgen. L. Verlingue: Financial Interests, Personal, Other, Personal fees: Adaptherapy; Financial Interests, Other, non-personal fees: Pierre-Fabre; Financial Interests, Other, non-personal fees: Servier; Financial Interests, Personal, Other, Grants: Bristol-Myers Squibb. G. Roubaud: Financial Interests, Other, Honoraria: Astellas pharma; Financial Interests, Other, Honoraria: Janssen-cilag; Financial Interests, Other, Honoraria: Sanofi; Financial Interests, Other, Honoraria: AstraZeneca; Financial Interests, Other, Honoraria: Ipsen; Financial Interests, Other, Honoraria: Pfizer; Financial Interests, Research Grant: Bayer. L. Friboulet: Financial Interests, Institutional, Research Grant: Debiopharm; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Relay Therapeutics. J-C. Soria: Non-Financial Interests, Personal, Advisory Board: Hookipa Pharmaceutical; Financial Interests, Personal, Stocks/Shares: AstraZeneca; Financial Interests, Personal, Stocks/Shares: relay therapeutics; Financial Interests, Personal, Stocks/Shares: Gritstone Oncology; Financial Interests, Personal, Full or part-time Employment: AstraZeneca. All other authors have declared no conflicts of interest.