FGFR-altered, advanced urothelial carcinoma (UC) and response to chemotherapy prior to receiving erdafitinib.

Andrea Necchi Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy info_outline Andrea Necchi, Arlene O. Siefker-Radtke, Bob Zhong, Parthiv Jasvant Mahadevia, Ademi E. Santiago-Walker, Peter De Porre, Yohann Loriot

Authors Andrea Necchi Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy info_outline Andrea Necchi, Arlene O. Siefker-Radtke, Bob Zhong, Parthiv Jasvant Mahadevia, Ademi E. Santiago-Walker, Peter De Porre, Yohann Loriot Organizations Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, The University of Texas MD Anderson Cancer Center, Houston, TX, Janssen Research & Development, Spring House, PA, Janssen Research & Development, Raritan, NJ, Janssen Research & Development, Beerse, Belgium, Institut de Cancérologie Gustave Roussy, Villejuif, France Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: FGFR-altered, advanced UC has predominantly a luminal 1 subtype, which is associated with lower response rates to immunotherapy and possibly also to chemotherapy. Objective response rates (ORR) for first-line cisplatin-based regimens, such as gemcitabine-cisplatin (gem/cis) and methotrexate-vinblastine-doxorubicin-cisplatin (MVAC), historically range between 45-60% and for gemcitabine-carboplatin (gem/carbo) 35-45%. However, the ORR on chemotherapy for the ~20% of patients with FGFR-altered tumors is unknown. Methods: BLC2001 (NCT02365597) is an ongoing global open-label phase 2 study of the pan-FGFR inhibitor erdafitinib in patients with locally advanced or metastatic UC with specific FGFR2/3 gene alterations. Patients who had received first-line (1L) or second-line (2L) chemotherapy for advanced UC were identified. Investigator-reported ORR (complete + partial responses) and median time to progression (TTP) on these pretreatments were analyzed. Results: Of 210 patients treated with erdafitinib in BLC2001, 191 had received prior systemic therapy including 184 and 83 patients who had received 1L and 2L chemotherapy, respectively. ORR were 29.3% (54/184; 95% CI 22.8%, 35.9%) to 1L chemotherapy and 24.1% (20/83; 95% CI 14.9%, 33.3%) to 2L chemotherapy. 1L therapy consisted of gem/cis in 94 patients, gem/carbo in 59 patients, and MVAC in 22 patients, with ORR (95% CI) of 35.1% (25.5%, 44.8%), 25.4% (14.3%, 36.5%), and 22.7% (5.2%, 40.2%), respectively. In the 2L setting, of 46 patients who had received a regimen containing a taxane (paclitaxel or docetaxel) or vinflunine, 8 patients (17.4%; 95% CI 6.4%, 28.3%) achieved an objective response. Median TTP was 7.16 mo (95% CI 6.18, 7.49) after 1L chemotherapy (7.6 mo for gem/cis, 6.3 mo for gem/carbo, and 5.3 mo for MVAC) and 4.35 mo (95% CI 3.3, 5.5) after 2L chemotherapy (3.6 mo for taxane or vinflunine). Conclusions: In this post-hoc analysis, the overall ORR to prior 1L chemotherapy was lower, but within the range expected based on historical data. Further investigation into the response to chemotherapy in FGFR alteration positive patients is warranted and may be useful for the development of 1L trials of combination therapy. Clinical trial information: NCT02365597