- Email: [email protected]
Analysis of response to prior therapies and therapies after treatment with erdafitinib in fibroblast growth factor receptor (FGFR)-positive patients (pts) with metastatic urothelial carcinoma (mUC)
abstracts
924P
Pathologic outcomes after neoadjuvant chemotherapy for high-risk muscle invasive bladder cancer
J.T. Matulay1, M.T. Campbell2, V.M. Narayan1, M.A. Seif1, A.H. Lim1, A.Y. Shah2, P. Msaouel2, J. Gao2, A.O. Siefker-Radtke2, C.P.N. Dinney1, A.M. Kamat1, N. Navai1 1 Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 2Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Background: Neoadjuvant chemotherapy (NAC) with cisplatin-based chemotherapy for muscle invasive bladder cancer (MIBC) has improves overall survival as compared to radical cystectomy (RC) alone. Our group has previously reported high risk features of MIBC that increase benefit of NAC. We report our institutional experience with NAC for patients with high-risk MIBC. Methods: The records of consecutive high-risk, clinically node negative MIBC patients who underwent RC at our institution between 2005 and 2017 were reviewed. Pre-operative high-risk criteria included one or more of lymphovascular invasion, hydronephrosis, extravesical disease, and/or variant histology. Clinicopathologic and demographic information was collected, including eGFR and a previously validated frailty index. The primary outcomes were pathologic complete response (pCR¼pT0N0M0) and downstaging to
v370 | Genitourinary Tumours, Non-Prostate
survival were: 90% and 63% (MVAC); 85% and 47% (GC); 86% and 54% (OCBR); 81% and 50% (NCBR); 81% and 47% (none). Conclusions: The benefits of NAC for MIBC have been repeatedly demonstrated, however, the rate of pathologic CR in high-risk muscle invasive disease has not been reported in a large series. In our high risk MIBC group, NAC led to significant higher pCR rate as compared to upfront surgery. These findings will serve as a benchmark for future neoadjuvant studies for evaluation of novel regimens. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: M.T. Campbell: Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): EMD Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Apricity health; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Janssen; Non-remunerated activity/ies: BMS; Non-remunerated activity/ies: Roche; Non-remunerated activity/ies: Merck. A.Y. Shah: Honoraria (self), Research grant / Funding (institution): Eisai; Honoraria (self): Oncology Information Group; Honoraria (self): Roche Pharmaceuticals; Research grant / Funding (institution): BMS; Research grant / Funding (institution): EMD Serono. J. Gao: Travel / Accommodation / Expenses: AstraZeneca. A.O. Siefker-Radtke: Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Sharp & Dohme; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Travel / Accommodation / Expenses: Nektar Therapeutics; Advisory / Consultancy, Travel / Accommodation / Expenses: Seattle Genetics; Advisory / Consultancy: Bavarian Nordic. C.P.N. Dinney: Advisory / Consultancy: FKD Therapies Oy; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (self): NCI; Research grant / Funding (self): The University of Eastern Finland, Faculty of Health Sciences (UEFHS). A.M. Kamat: Advisory / Consultancy: Photocure; Advisory / Consultancy: FKD; Advisory / Consultancy: Abbott Molecular; Advisory / Consultancy: Theralase; Advisory / Consultancy: Merck; Advisory / Consultancy: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: BioClin Therapeutics; Advisory / Consultancy: Cold Genesys; Advisory / Consultancy: Roviant; Advisory / Consultancy: Sessen Bio; Advisory / Consultancy: Asieris; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: US Biotest; Advisory / Consultancy: Ferring; Advisory / Consultancy: MDxHealth; Leadership role: IBCG; Advisory / Consultancy: TMC Innovation. N. Navai: Shareholder / Stockholder / Stock options: Allogene; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Pacira. All other authors have declared no conflicts of interest.
925P
Analysis of response to prior therapies and therapies after treatment with erdafitinib in fibroblast growth factor receptor (FGFR)-positive patients (pts) with metastatic urothelial carcinoma (mUC)
A. Siefker-Radtke1, B. Zhong2, K. Qi3, W. Shalaby4, P. De Porre5, A. O’Hagan6, P. Mahadevia7, Y. Loriot8 1 Genitourinary Medical Oncology, The M. D. Anderson Cancer Center, Houston, TX, USA, 2Clinical Biostatistics, Janssen Research & Development, LLC, Spring House, PA, USA, 3Statistics and Data Science, Janssen Research & Development, LLC, Titusville, NJ, USA, 4Medical Oncology, Janssen Research & Development, LLC, Horsham, PA, USA, 5 Clinical Oncology, Janssen EMEA Belgium, Beerse, Belgium, 6Clinical Oncology, Janssen Research & Development, Spring House, PA, USA, 7Global Medical Affairs, Janssen Pharmaceuticals, Raritan, NJ, USA, 8Department of Cancer Medicine, Gustave Roussy, Villejuif, France Background: Recently, erdafitinib (erda), a novel FGFR-targeted therapy received accelerated US FDA approval for locally-advanced or mUC in adult pts with FGFR2/3 alterations who progressed on prior 1st-line platinum-containing chemotherapy. The current analysis was performed to understand treatment response to prior and subsequent therapies in FGFRþ mUC pts treated with erda. Methods: Pts with surgically unresectable mUC who had failed 1 prior chemotherapy and received 8 mg once-daily erda in a phase 2 study (NCT02365597) were retrospectively assessed. Pts were grouped as cisplatin (C)-eligible (received 1st-line gemcitabine [G]-C or MVAC [methotrexate/vinblastine/doxorubicin/C]) or C-ineligible (received 1st-line G-carboplatin or checkpoint inhibitors). Treatment duration, time to progression (TTP) and response to prior chemotherapy (objective response rate [ORR] and disease control rate [DCR]), progression-free survival (PFS), overall survival (OS), and subsequent response after erda therapy were assessed using investigator reported outcomes. Results: In this analysis, the median duration of treatment (time from 1st dose of 1st line to 1st dose of 2nd line) with 1st-line chemotherapy was 10.07 months for C-eligible (n ¼ 52) and 8.02 months for C-ineligible (n ¼ 34) pts; 31 pts received prior 2nd-line chemotherapy (median treatment duration: 9.23 months) and 10 received 3rd-line chemotherapy (median treatment duration: 6.26 months). The median TPP for prior 1stline therapy was longer than on 2nd or 3rd-line therapy (Table). In total, 34 patients received treatment (chemotherapy, n ¼ 19; immunotherapy, n ¼ 15) after erda and had median PFS of 2.27 months (95% CI: 0.79; 2.86) and median OS of 3.52 months (95% CI: 2.04; 8.90).
Volume 30 | Supplement 5 | October 2019
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Amgen; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Servier; Research grant / Funding (self): Merck. C. Serrano: Advisory / Consultancy, Research grant / Funding (institution): Deciphera; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Blueprint; Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Lilly. E. Garralda: Advisory / Consultancy, Research grant / Funding (institution): Roche/ Genentech; Advisory / Consultancy: Ellipses Pharma; Advisory / Consultancy: Neomed Therapeutics; Advisory / Consultancy: Boeringer Ingelheim; Advisory / Consultancy: Janssen Global Services; Speaker Bureau / Expert testimony: BMS; Travel / Accommodation / Expenses: Merck; Research grant / Funding (institution), Travel / Accommodation / Expenses: Glycotope; Research grant / Funding (institution), Travel / Accommodation / Expenses: Menarini; Research grant / Funding (self), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Principia Biopharma; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Loxo Oncology; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): Merck; Honoraria (institution): Incyte; Research grant / Funding (institution): Pharma Mar; Research grant / Funding (institution): Kura Oncology; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Pierre Fabre; Research grant / Funding (institution): Cellestia; Research grant / Funding (institution): Blueprint; Research grant / Funding (institution): Beigene; Research grant / Funding (institution): Sierra; Research grant / Funding (institution): Genmab. J. Carles: Research grant / Funding (institution): AB Science; Research grant / Funding (institution): Aragon Pharmaceuticals; Research grant / Funding (institution): Arog Pharmaceuticals; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas Pharma; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca AB; Research grant / Funding (institution): Aveo Pharmaceuticals INC; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer AG; Research grant / Funding (institution): Blueprint Medicines Corporation; Research grant / Funding (institution): BN Immunotherapeutics INC; Research grant / Funding (institution): Boehringer Ingelheim Espa~ na; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb International Corporation (BMS),; Research grant / Funding (institution): Clovis Oncology, INC; Research grant / Funding (institution): Cougar Biotechnology INC; Research grant / Funding (institution): Deciphera Pharmaceuticals LLC; Research grant / Funding (institution): Exelixis INC; Research grant / Funding (institution): F. Hoffmann-La Roche LTD, Genentech INC,; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Janssen-Cilag International NV; Research grant / Funding (institution): Karyopharm Therapeutics; Research grant / Funding (institution): Laboratoires Leurquin Mediolanum SAS; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Medimmune; Research grant / Funding (institution): Millennium Pharmaceuticals; Research grant / Funding (institution): Nanobiotix SA; Research grant / Funding (institution): Novartis Farmace´utica; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): SFJ Pharma LTD. II; Research grant / Funding (institution): Teva Pharma S.L.U.; Advisory / Consultancy, Speaker Bureau / Expert testimony: Johnson & Johnson; Advisory / Consultancy, Research grant / Funding (institution): SanofiAventis; Advisory / Consultancy, Research grant / Funding (institution): MSD Oncology; Advisory / Consultancy, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony: Asofarma. All other authors have declared no conflicts of interest.
Annals of Oncology
abstracts
Annals of Oncology
Table: 925P Efficacy results on prior and subsequent treatments Median TTP (95% CI), months
ORR (CRþPR) (%)
DCR (CRþPRþ SD) (%)
1st-line chemotherapy (n ¼ 84) C-eligible C-ineligible 2nd-line chemotherapy (n ¼ 31) 2nd-line D/V/P 3rd-line chemotherapy (n ¼ 10) 3rd-line D/V/P Therapy after erda (n ¼ 34) 1st-line after erda 1st-line chemotherapy 1st-line immunotherapy 2nd-line after erda 2nd-line chemotherapy 2nd-line immunotherapy
7.34 (5.91; 8.80) 8.84 (6.37; 10.38) 6.59 (3.06; 7.49) 7.13 (3.78; 9.36) 7.13 (3.06; 10.48) 5.70 (2.33; 8.64) 5.55 (2.99; 9.46) ORR (%) 1/34 (2.9) 0/16 1/15 (6.7) 1/9 (11.1) 0/7 1/2 (50.0)
28/84 (33.3) 18/52 (34.6) 9/34 (26.5) 11/31 (35.5) 6/16 (37.5) 2/10 (20.0) 1/7 (14.3)
49/84 (58.3) 31/52 (59.6) 18/34 (52.9) 21/31 (67.7) 10/16 (62.5) 5/10 (50.0) 3/7 (42.9) DCR (%) 3/34 (8.8) 0/16 3/15 (20.0) 1/9 (11.1) 0/7 1/2 (50.0)
CR, complete response; D/V/P, docetaxel/vinflunine/paclitaxel; PR, partial response; SD, stable disease.
Conclusions: These results provide insights into treatment responses in a unique population of FGFRþ mUC pts. Clinical trial identification: NCT02365597. Editorial acknowledgement: Priya Ganpathy, MPharm, ISMPP CMPPTM (SIRO Clinpharm Pvt. Ltd., India) provided writing assistance and Harry Ma, PhD (Janssen Global Services, LLC) provided additional editorial support. Legal entity responsible for the study: Janssen Research & Development, LLC. Funding: Janssen Research & Development, LLC. Disclosure: A.O. Siefker-Radtke: Advisory / Consultancy: Janssen, Threshold Pharmaceuticals, Merck, National Comprehensive Cancer Network, Eisai, Genentech, Vertex, AstraZeneca, EMD Serono, Bristol-Myers Squibb; Research grant / Funding (self): National Institutes of Health, Genentech, Janssen Pharmaceuticals, Millennium, Michael and Sherry Sutton Fund for Urothelial Cancer; Speaker Bureau / Expert testimony: Genentech. B. Zhong: Shareholder / Stockholder / Stock
Table: 926P MAIC results for base case scenario: Erda (in FGFR
Volume 30 | Supplement 5 | October 2019
926P
Erdafitinib (erda) versus available therapies in advanced urothelial cancer: A matching adjusted indirect comparison
Y. Loriot1, S. Van Sanden2, J. Diels2, N. Rahhali3, D. Seshagiri4, B. Kowalski5, S. Fleming6, P. De Porre7, A.O. Siefker-Radtke8 1 Cancer Medicine Department, Institut Gustave Roussy, Villejuif, France, 2HEMAR EMEA Department, Janssen Pharmaceutica NV - Belgium, Beerse, Belgium, 3HEMAR EMEA Department, Janssen Cilag France, Issy Les Moulineaux, France, 4HEMAR EMEA Department, Janssen-Cilag Germany, North Rhine-Westphalia, Germany, 5Health Economy, Janssen Cilag France, Issy Les Moulineaux, France, 6Oncology, Janssen R&D US, Titusville, NJ, USA, 7Clinical Oncology, Janssen R&D, Belgium, Beerse, Belgium, 8Ongology, MD Anderson Cancer Center, Houston, TX, USA Background: Erda, a pan-fibroblast growth factor receptor (FGFR) inhibitor recently received accelerated US FDA approval for locally advanced or metastatic urothelial cancer (mUC) in adult patients (pts) with FGFR2/3 alterations who progressed on 1 prior platinum-containing chemotherapy, based on a single-arm phase 2 study. In the absence of head-to-head studies, a matching-adjusted indirect comparison (MAIC) was used to compare the efficacy of erda relative to available therapies in mUC pts. Methods: Systematic literature review was performed to identify published randomized controlled trials (RCTs) of 2nd-line treatments (from 1990-on) in mUC pts with unknown FGFR status. Individual patient-level data (IPD) were used from the phase 2 study (NCT02365597) in mUC pts treated with erda (8 mg/day). ORR (primary endpoint), overall survival (OS) and progression-free survival (PFS) were compared using an unanchored MAIC. The IPD were weighted to match the aggregated data from comparator studies. Results: Nine relevant RCTs of 6 comparators (docetaxel [D], vinflunine [V], pembrolizumab [Pb], atezolizumab [A], paclitaxel [P], and mixed-chemotherapy [D, V or P]) that were identified could be matched with. The matching-adjusted odds ratios (OR) for ORR were consistently >1 vs all comparators, suggesting higher ORR with erda treatment over all comparator 2nd-line therapies. The matching-adjusted hazard ratios (HRs) for OS and PFS vs all comparators were <1, suggesting better outcomes (PFS/ OS) with erda. Results from the sensitivity analyses showed varied statistical significance, however, the overall trends were relatively similar. Study limitations: availability of comparable endpoints and baseline characteristics; small sample size of the erda study.
pts) vs available 2nd-line therapies in pts with unknown FGFR status
doi:10.1093/annonc/mdz249 | v371
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Prior therapy
options, Employee and stockholder: Janssen Research & Development. K. Qi: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. W.S. Shalaby: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. P. De Porre: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. A. O’Hagan: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development, LLC. P. Mahadevia: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. Y. Loriot: Advisory / Consultancy: Astellas Oncology; AstraZeneca; Ipsen; Janssen; MSD; Roche; Sanofi; Research grant / Funding (self): Sanofi (Inst); Travel / Accommodation / Expenses: AstraZeneca; MSD; Roche.
924P
Pathologic outcomes after neoadjuvant chemotherapy for high-risk muscle invasive bladder cancer
J.T. Matulay1, M.T. Campbell2, V.M. Narayan1, M.A. Seif1, A.H. Lim1, A.Y. Shah2, P. Msaouel2, J. Gao2, A.O. Siefker-Radtke2, C.P.N. Dinney1, A.M. Kamat1, N. Navai1 1 Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 2Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Background: Neoadjuvant chemotherapy (NAC) with cisplatin-based chemotherapy for muscle invasive bladder cancer (MIBC) has improves overall survival as compared to radical cystectomy (RC) alone. Our group has previously reported high risk features of MIBC that increase benefit of NAC. We report our institutional experience with NAC for patients with high-risk MIBC. Methods: The records of consecutive high-risk, clinically node negative MIBC patients who underwent RC at our institution between 2005 and 2017 were reviewed. Pre-operative high-risk criteria included one or more of lymphovascular invasion, hydronephrosis, extravesical disease, and/or variant histology. Clinicopathologic and demographic information was collected, including eGFR and a previously validated frailty index. The primary outcomes were pathologic complete response (pCR¼pT0N0M0) and downstaging to
v370 | Genitourinary Tumours, Non-Prostate
survival were: 90% and 63% (MVAC); 85% and 47% (GC); 86% and 54% (OCBR); 81% and 50% (NCBR); 81% and 47% (none). Conclusions: The benefits of NAC for MIBC have been repeatedly demonstrated, however, the rate of pathologic CR in high-risk muscle invasive disease has not been reported in a large series. In our high risk MIBC group, NAC led to significant higher pCR rate as compared to upfront surgery. These findings will serve as a benchmark for future neoadjuvant studies for evaluation of novel regimens. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: M.T. Campbell: Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): EMD Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Apricity health; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Janssen; Non-remunerated activity/ies: BMS; Non-remunerated activity/ies: Roche; Non-remunerated activity/ies: Merck. A.Y. Shah: Honoraria (self), Research grant / Funding (institution): Eisai; Honoraria (self): Oncology Information Group; Honoraria (self): Roche Pharmaceuticals; Research grant / Funding (institution): BMS; Research grant / Funding (institution): EMD Serono. J. Gao: Travel / Accommodation / Expenses: AstraZeneca. A.O. Siefker-Radtke: Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Sharp & Dohme; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Travel / Accommodation / Expenses: Nektar Therapeutics; Advisory / Consultancy, Travel / Accommodation / Expenses: Seattle Genetics; Advisory / Consultancy: Bavarian Nordic. C.P.N. Dinney: Advisory / Consultancy: FKD Therapies Oy; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (self): NCI; Research grant / Funding (self): The University of Eastern Finland, Faculty of Health Sciences (UEFHS). A.M. Kamat: Advisory / Consultancy: Photocure; Advisory / Consultancy: FKD; Advisory / Consultancy: Abbott Molecular; Advisory / Consultancy: Theralase; Advisory / Consultancy: Merck; Advisory / Consultancy: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: BioClin Therapeutics; Advisory / Consultancy: Cold Genesys; Advisory / Consultancy: Roviant; Advisory / Consultancy: Sessen Bio; Advisory / Consultancy: Asieris; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: US Biotest; Advisory / Consultancy: Ferring; Advisory / Consultancy: MDxHealth; Leadership role: IBCG; Advisory / Consultancy: TMC Innovation. N. Navai: Shareholder / Stockholder / Stock options: Allogene; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Pacira. All other authors have declared no conflicts of interest.
925P
Analysis of response to prior therapies and therapies after treatment with erdafitinib in fibroblast growth factor receptor (FGFR)-positive patients (pts) with metastatic urothelial carcinoma (mUC)
A. Siefker-Radtke1, B. Zhong2, K. Qi3, W. Shalaby4, P. De Porre5, A. O’Hagan6, P. Mahadevia7, Y. Loriot8 1 Genitourinary Medical Oncology, The M. D. Anderson Cancer Center, Houston, TX, USA, 2Clinical Biostatistics, Janssen Research & Development, LLC, Spring House, PA, USA, 3Statistics and Data Science, Janssen Research & Development, LLC, Titusville, NJ, USA, 4Medical Oncology, Janssen Research & Development, LLC, Horsham, PA, USA, 5 Clinical Oncology, Janssen EMEA Belgium, Beerse, Belgium, 6Clinical Oncology, Janssen Research & Development, Spring House, PA, USA, 7Global Medical Affairs, Janssen Pharmaceuticals, Raritan, NJ, USA, 8Department of Cancer Medicine, Gustave Roussy, Villejuif, France Background: Recently, erdafitinib (erda), a novel FGFR-targeted therapy received accelerated US FDA approval for locally-advanced or mUC in adult pts with FGFR2/3 alterations who progressed on prior 1st-line platinum-containing chemotherapy. The current analysis was performed to understand treatment response to prior and subsequent therapies in FGFRþ mUC pts treated with erda. Methods: Pts with surgically unresectable mUC who had failed 1 prior chemotherapy and received 8 mg once-daily erda in a phase 2 study (NCT02365597) were retrospectively assessed. Pts were grouped as cisplatin (C)-eligible (received 1st-line gemcitabine [G]-C or MVAC [methotrexate/vinblastine/doxorubicin/C]) or C-ineligible (received 1st-line G-carboplatin or checkpoint inhibitors). Treatment duration, time to progression (TTP) and response to prior chemotherapy (objective response rate [ORR] and disease control rate [DCR]), progression-free survival (PFS), overall survival (OS), and subsequent response after erda therapy were assessed using investigator reported outcomes. Results: In this analysis, the median duration of treatment (time from 1st dose of 1st line to 1st dose of 2nd line) with 1st-line chemotherapy was 10.07 months for C-eligible (n ¼ 52) and 8.02 months for C-ineligible (n ¼ 34) pts; 31 pts received prior 2nd-line chemotherapy (median treatment duration: 9.23 months) and 10 received 3rd-line chemotherapy (median treatment duration: 6.26 months). The median TPP for prior 1stline therapy was longer than on 2nd or 3rd-line therapy (Table). In total, 34 patients received treatment (chemotherapy, n ¼ 19; immunotherapy, n ¼ 15) after erda and had median PFS of 2.27 months (95% CI: 0.79; 2.86) and median OS of 3.52 months (95% CI: 2.04; 8.90).
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Amgen; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Servier; Research grant / Funding (self): Merck. C. Serrano: Advisory / Consultancy, Research grant / Funding (institution): Deciphera; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Blueprint; Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Lilly. E. Garralda: Advisory / Consultancy, Research grant / Funding (institution): Roche/ Genentech; Advisory / Consultancy: Ellipses Pharma; Advisory / Consultancy: Neomed Therapeutics; Advisory / Consultancy: Boeringer Ingelheim; Advisory / Consultancy: Janssen Global Services; Speaker Bureau / Expert testimony: BMS; Travel / Accommodation / Expenses: Merck; Research grant / Funding (institution), Travel / Accommodation / Expenses: Glycotope; Research grant / Funding (institution), Travel / Accommodation / Expenses: Menarini; Research grant / Funding (self), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Principia Biopharma; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Loxo Oncology; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): Merck; Honoraria (institution): Incyte; Research grant / Funding (institution): Pharma Mar; Research grant / Funding (institution): Kura Oncology; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Pierre Fabre; Research grant / Funding (institution): Cellestia; Research grant / Funding (institution): Blueprint; Research grant / Funding (institution): Beigene; Research grant / Funding (institution): Sierra; Research grant / Funding (institution): Genmab. J. Carles: Research grant / Funding (institution): AB Science; Research grant / Funding (institution): Aragon Pharmaceuticals; Research grant / Funding (institution): Arog Pharmaceuticals; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas Pharma; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca AB; Research grant / Funding (institution): Aveo Pharmaceuticals INC; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer AG; Research grant / Funding (institution): Blueprint Medicines Corporation; Research grant / Funding (institution): BN Immunotherapeutics INC; Research grant / Funding (institution): Boehringer Ingelheim Espa~ na; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb International Corporation (BMS),; Research grant / Funding (institution): Clovis Oncology, INC; Research grant / Funding (institution): Cougar Biotechnology INC; Research grant / Funding (institution): Deciphera Pharmaceuticals LLC; Research grant / Funding (institution): Exelixis INC; Research grant / Funding (institution): F. Hoffmann-La Roche LTD, Genentech INC,; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Janssen-Cilag International NV; Research grant / Funding (institution): Karyopharm Therapeutics; Research grant / Funding (institution): Laboratoires Leurquin Mediolanum SAS; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Medimmune; Research grant / Funding (institution): Millennium Pharmaceuticals; Research grant / Funding (institution): Nanobiotix SA; Research grant / Funding (institution): Novartis Farmace´utica; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): SFJ Pharma LTD. II; Research grant / Funding (institution): Teva Pharma S.L.U.; Advisory / Consultancy, Speaker Bureau / Expert testimony: Johnson & Johnson; Advisory / Consultancy, Research grant / Funding (institution): SanofiAventis; Advisory / Consultancy, Research grant / Funding (institution): MSD Oncology; Advisory / Consultancy, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony: Asofarma. All other authors have declared no conflicts of interest.
Annals of Oncology
abstracts
Annals of Oncology
Table: 925P Efficacy results on prior and subsequent treatments Median TTP (95% CI), months
ORR (CRþPR) (%)
DCR (CRþPRþ SD) (%)
1st-line chemotherapy (n ¼ 84) C-eligible C-ineligible 2nd-line chemotherapy (n ¼ 31) 2nd-line D/V/P 3rd-line chemotherapy (n ¼ 10) 3rd-line D/V/P Therapy after erda (n ¼ 34) 1st-line after erda 1st-line chemotherapy 1st-line immunotherapy 2nd-line after erda 2nd-line chemotherapy 2nd-line immunotherapy
7.34 (5.91; 8.80) 8.84 (6.37; 10.38) 6.59 (3.06; 7.49) 7.13 (3.78; 9.36) 7.13 (3.06; 10.48) 5.70 (2.33; 8.64) 5.55 (2.99; 9.46) ORR (%) 1/34 (2.9) 0/16 1/15 (6.7) 1/9 (11.1) 0/7 1/2 (50.0)
28/84 (33.3) 18/52 (34.6) 9/34 (26.5) 11/31 (35.5) 6/16 (37.5) 2/10 (20.0) 1/7 (14.3)
49/84 (58.3) 31/52 (59.6) 18/34 (52.9) 21/31 (67.7) 10/16 (62.5) 5/10 (50.0) 3/7 (42.9) DCR (%) 3/34 (8.8) 0/16 3/15 (20.0) 1/9 (11.1) 0/7 1/2 (50.0)
CR, complete response; D/V/P, docetaxel/vinflunine/paclitaxel; PR, partial response; SD, stable disease.
Conclusions: These results provide insights into treatment responses in a unique population of FGFRþ mUC pts. Clinical trial identification: NCT02365597. Editorial acknowledgement: Priya Ganpathy, MPharm, ISMPP CMPPTM (SIRO Clinpharm Pvt. Ltd., India) provided writing assistance and Harry Ma, PhD (Janssen Global Services, LLC) provided additional editorial support. Legal entity responsible for the study: Janssen Research & Development, LLC. Funding: Janssen Research & Development, LLC. Disclosure: A.O. Siefker-Radtke: Advisory / Consultancy: Janssen, Threshold Pharmaceuticals, Merck, National Comprehensive Cancer Network, Eisai, Genentech, Vertex, AstraZeneca, EMD Serono, Bristol-Myers Squibb; Research grant / Funding (self): National Institutes of Health, Genentech, Janssen Pharmaceuticals, Millennium, Michael and Sherry Sutton Fund for Urothelial Cancer; Speaker Bureau / Expert testimony: Genentech. B. Zhong: Shareholder / Stockholder / Stock
Table: 926P MAIC results for base case scenario: Erda (in FGFR
Volume 30 | Supplement 5 | October 2019
926P
Erdafitinib (erda) versus available therapies in advanced urothelial cancer: A matching adjusted indirect comparison
Y. Loriot1, S. Van Sanden2, J. Diels2, N. Rahhali3, D. Seshagiri4, B. Kowalski5, S. Fleming6, P. De Porre7, A.O. Siefker-Radtke8 1 Cancer Medicine Department, Institut Gustave Roussy, Villejuif, France, 2HEMAR EMEA Department, Janssen Pharmaceutica NV - Belgium, Beerse, Belgium, 3HEMAR EMEA Department, Janssen Cilag France, Issy Les Moulineaux, France, 4HEMAR EMEA Department, Janssen-Cilag Germany, North Rhine-Westphalia, Germany, 5Health Economy, Janssen Cilag France, Issy Les Moulineaux, France, 6Oncology, Janssen R&D US, Titusville, NJ, USA, 7Clinical Oncology, Janssen R&D, Belgium, Beerse, Belgium, 8Ongology, MD Anderson Cancer Center, Houston, TX, USA Background: Erda, a pan-fibroblast growth factor receptor (FGFR) inhibitor recently received accelerated US FDA approval for locally advanced or metastatic urothelial cancer (mUC) in adult patients (pts) with FGFR2/3 alterations who progressed on 1 prior platinum-containing chemotherapy, based on a single-arm phase 2 study. In the absence of head-to-head studies, a matching-adjusted indirect comparison (MAIC) was used to compare the efficacy of erda relative to available therapies in mUC pts. Methods: Systematic literature review was performed to identify published randomized controlled trials (RCTs) of 2nd-line treatments (from 1990-on) in mUC pts with unknown FGFR status. Individual patient-level data (IPD) were used from the phase 2 study (NCT02365597) in mUC pts treated with erda (8 mg/day). ORR (primary endpoint), overall survival (OS) and progression-free survival (PFS) were compared using an unanchored MAIC. The IPD were weighted to match the aggregated data from comparator studies. Results: Nine relevant RCTs of 6 comparators (docetaxel [D], vinflunine [V], pembrolizumab [Pb], atezolizumab [A], paclitaxel [P], and mixed-chemotherapy [D, V or P]) that were identified could be matched with. The matching-adjusted odds ratios (OR) for ORR were consistently >1 vs all comparators, suggesting higher ORR with erda treatment over all comparator 2nd-line therapies. The matching-adjusted hazard ratios (HRs) for OS and PFS vs all comparators were <1, suggesting better outcomes (PFS/ OS) with erda. Results from the sensitivity analyses showed varied statistical significance, however, the overall trends were relatively similar. Study limitations: availability of comparable endpoints and baseline characteristics; small sample size of the erda study.
pts) vs available 2nd-line therapies in pts with unknown FGFR status
doi:10.1093/annonc/mdz249 | v371
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Prior therapy
options, Employee and stockholder: Janssen Research & Development. K. Qi: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. W.S. Shalaby: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. P. De Porre: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. A. O’Hagan: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development, LLC. P. Mahadevia: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. Y. Loriot: Advisory / Consultancy: Astellas Oncology; AstraZeneca; Ipsen; Janssen; MSD; Roche; Sanofi; Research grant / Funding (self): Sanofi (Inst); Travel / Accommodation / Expenses: AstraZeneca; MSD; Roche.