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Expert Review of Precision Medicine and Drug Development
Personalized medicine in drug development and clinical practice
Volume 4, 2019 - Issue 2
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Review

Precision therapy in advanced urothelial cancer

, , & ORCID Icon
Pages 81-93 | Received 25 Dec 2018, Accepted 11 Feb 2019, Published online: 05 Mar 2019

References

  • American Cancer Society. (2018, September 25). Cancer facts and figures 2018 [cited 2018 Dec 12]. Available from: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf
  • Sanli O, Dobruch J, Knowles MA, et al. Bladder cancer. Nat Rev Dis Primers. 2017;3:17022.
  • Hedegaard J, Lamy P, Nordentoft I, et al. Comprehensive transcriptional analysis of early-stage urothelial carcinoma. Cancer Cell. 2016;30(1):27–42.
  • Damrauer JS, Hoadley KA, Chism DD, et al. Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc Natl Acad Sci U S A. 2014;111(8):3110–3115.
  • Choi W, Ochoa A, McConkey DJ, et al. Genetic alterations in the molecular subtypes of bladder cancer: illustration in the cancer genome atlas dataset. Eur Urol. 2017;72(3):354–365.
  • Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014; 507(7492): 315–322.
  • Sjodahl G, Lauss M, Lovgren K, et al. A molecular taxonomy for urothelial carcinoma. Clin Cancer Res. 2012;18(12):3377–3386.
  • Warrick JI, Walter V, Yamashita H, et al. FOXA1, GATA3 and PPAR cooperate to drive luminal subtype in bladder cancer: a molecular analysis of established human cell lines. Sci Rep. 2016;6:38531.
  • Robertson AG, Kim J, Al-Ahmadie H, et al. Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell. 2017;171(3):540–556.e25.
  • Ross JS, Wang K, Khaira D, et al. Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder reveals a high frequency of clinically relevant genomic alterations. Cancer. 2016;122(5):702–711.
  • Sfakianos JP, Cha EK, Iyer G, et al. Genomic characterization of upper tract urothelial carcinoma. Eur Urol. 2015;68(6):970–977.
  • Carlo MI, Vijai J, Mandelker D, et al. DNA damage repair (DDR) germline mutations in patients (Pts) with urothelial carcinoma (UC). J Clin Oncol. 2018;36(suppl_15):1516.
  • Klek S, Heald B, Milinovich A, et al. Genetic counseling (GC) and germline (GL) testing rates after adoption of an integrated clinical cancer genetics (CCG) approach to genomics tumor board (GTB). J Clin Oncol. 2018;36(suppl_15):1511.
  • Sadaps M, Funchain P, Mahdi H, et al. Precision oncology in solid tumors: a longitudinal tertiary care center experience. J Clin Oncol. 2018;2:1–11.
  • Agarwal N, Pal SK, Hahn AW, et al. Characterization of metastatic urothelial carcinoma via comprehensive genomic profiling of circulating tumor DNA. Cancer. 2018;124(10):2115–2124.
  • Merker JD, Oxnard GR, Compton C, et al. Circulating tumor DNA analysis in patients with cancer: american society of clinical oncology and college of american pathologists joint review. J Clin Oncol. 2018;36(16):1631–1641.
  • Grivas P, Nagy RJ, Pond GR, et al. Circulating tumor (ct)-DNA alterations in advanced urothelial carcinoma: association with outcomes and evolution with therapy. J Clin Oncol. 2017;25(suppl_6):334.
  • Borah S, Xi L, Zaug AJ, et al. Cancer. TERT promoter mutations and telomerase reactivation in urothelial cancer. Science. 2015;347(6225):1006–1010.
  • Lamarca A, Barriuso J. Urine telomerase for diagnosis and surveillance of bladder cancer. Adv Urol. 2012;2012:693631.
  • Barata PC, Koshkin VS, Funchain P, et al. Next-generation sequencing (NGS) of cell-free circulating tumor DNA and tumor tissue in patients with advanced urothelial cancer: a pilot assessment of concordance. Ann Oncol. 2017;28(10):2458–2463.
  • Hovelson DH, Udager AM, McDaniel AS, et al. Targeted DNA and RNA sequencing of paired urothelial and squamous bladder cancers reveals discordant genomic and transcriptomic events and unique therapeutic implications. Eur Urol. 2018;74(6):741–753.
  • Yi X, Ma J, Guan Y, et al. The feasibility of using mutation detection in ctDNA to assess tumor dynamics. Int J Cancer. 2017;140(12):2642–2647.
  • Ilie M, Hofman V, Long E, et al. Current challenges for detection of circulating tumor cells and cell-free circulating nucleic acids, and their characterization in non-small cell lung carcinoma patients. What is the best blood substrate for personalized medicine? Ann Transl Med. 2014;2(11):107.
  • Molparia B, Nichani E, Torkamani A. Assessment of circulating copy number variant detection for cancer screening. PLoS One. 2017;12(7):e0180647.
  • Jung Y, Lippard SJ. Direct cellular responses to platinum-induced DNA damage. Chem Rev. 2007;107(5):1387–1407.
  • Van Allen EM, Mouw KW, Kim P, et al. Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma. Cancer Discov. 2014;4(10):1140–1153.
  • Li Q, Damish A, Frazier ZJ, et al. ERCC2 helicase domain mutations confer nucleotide excision repair deficiency and drive cisplatin sensitivity in muscle-invasive bladder cancer. Clin Cancer Res. 2018. DOI:10.1158/1078-0432.CCR-18-1001.
  • Grivas P. DNA damage response gene alterations in urothelial cancer: ready for practice? Clin Cancer Res. 2018. DOI:10.1158/1078-0432.CCR-18-2512
  • Plimack ER, Dunbrack RL, Brennan TA, et al. Defects in DNA repair genes predict response to neoadjuvant cisplatin-based chemotherapy in muscle-invasive bladder dancer. Eur Urol. 2015;68(6):959–967.
  • Liu D, Plimack ER, Hoffman-Censits J, et al. Clinical validation of chemotherapy response biomarker ERCC2 in muscle-invasive urothelial bladder carcinoma. JAMA Oncol. 2016;2(8):1094–1096.
  • Seiler R, Ashab HAD, Erho N, et al. Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival after neoadjuvant chemotherapy. Eur Urol. 2017;72(4):544–554.
  • Hernandez S, Lopez-Knowles E, Lloreta J, et al. Prospective study of FGFR3 mutations as a prognostic factor in nonmuscle invasive urothelial bladder carcinomas. J Clin Oncol. 2006;24(22):3664–3671.
  • Tabernero J, Bahleda R, Dienstmann R, et al. Phase I dose-escalation study of JNJ-42756493, an oral pan-fibroblast growth factor receptor inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2015;33(30):3401–3408.
  • Siefker-Radtke AO, Necchi A, Park SH, et al. First results from the primary analysis population of the phase 2 study of erdafitinib (ERDA; JNJ-42756493) in patients (pts) with metastatic or unresectable urothelial carcinoma (mUC) and FGFR alterations (FGFRalt). J Clin Oncol. 2018;36(suppl_15):4503.
  • Joerger M, Cassier P, Penel N, et al. Rogaratinib treatment of patients with advanced urothelial carcinomas prescreened for tumor FGFR mRNA expression. J Clin Oncol. 2018;36(suppl_6):494.
  • Sequist LV, Cassier P, Varga A, et al. Abstract CT326: phase I study of BGJ398, a selective pan-FGFR inhibitor in genetically preselected advanced solid tumors. Cancer Res. 2014;suppl_19:CT326.
  • Necchi A, Pouessel D, Leibowitz-Amit R, et al. Interim results of fight-201, a phase II, open-label, multicenter study of INCB054828 in patients (pts) with metastatic or surgically unresectable urothelial carcinoma (UC) harboring fibroblast growth factor (FGF)/FGF receptor (FGFR) genetic alterations (GA). Ann Oncol. 2018;29(suppl_18):viii319-viii:320.
  • Yap TA, Omlin A, de Bono JS. Development of therapeutic combinations targeting major cancer signaling pathways. J Clin Oncol. 2013;31(12):1592–1605.
  • Eriksson P, Sjodahl G, Chebil G, et al. HER2 and EGFR amplification and expression in urothelial carcinoma occurs in distinct biological and molecular contexts. Oncotarget. 2017;8(30):48905–48914.
  • Mooso BA, Vinall RL, Mudryj M, et al. The role of EGFR family inhibitors in muscle invasive bladder cancer: a review of clinical data and molecular evidence. J Urol. 2015;193(1):19–29.
  • Grivas PD, Day M, Hussain M. Urothelial carcinomas: a focus on human epidermal receptors signaling. Am J Transl Res. 2011;3(4):362–373.
  • Wong YN, Litwin S, Vaughn D, et al. Phase II trial of cetuximab with or without paclitaxel in patients with advanced urothelial tract carcinoma. J Clin Oncol. 2012;30(28):3545–3551.
  • Hussain M, Daignault S, Agarwal N, et al. A randomized phase 2 trial of gemcitabine/cisplatin with or without cetuximab in patients with advanced urothelial carcinoma. Cancer. 2014;120(17):2684–2693.
  • Powles T, Huddart RA, Elliott T, et al. Phase III, double-blind, randomized trial that compared maintenance lapatinib versus placebo after first-line chemotherapy in patients with human epidermal growth factor receptor 1/2–positive metastatic bladder cancer. J Clin Oncol. 2017;35(1):48–55.
  • Choudhury NJ, Campanile A, Antic T, et al. Afatinib activity in platinum-refractory metastatic urothelial carcinoma in patients with ERBB alterations. J Clin Oncol. 2016;34(18):2165–2171.
  • Bellmunt J, Werner L, Bamias A, et al. HER2 as a target in invasive urothelial carcinoma. Cancer Med. 2015;4(6):844–852.
  • Ross JS, Wang K, Gay LM, et al. A high frequency of activating extracellular domain ERBB2 (HER2) mutation in micropapillary urothelial carcinoma. Clin Cancer Res. 2014;20(1):68–75.
  • Mejri N, Sellami R, Lamia C, et al. Status of HER2 over expression in muscle invasive urothelial bladder carcinoma: report of 21 cases. Urol Ann. 2014;6(1):63–67.
  • Kiss B, Wyatt AW, Douglas J, et al. HER2 alterations in muscle-invasive bladder cancer: patient selection beyond protein expression for targeted therapy. Sci Rep. 2017;7:42713.
  • Pal SK, Agarwal N, Choueiri TK, et al. Comparison of tumor mutational burden (TMB) in relevant molecular subsets of metastatic urothelial cancer (MUC). Ann Oncol. 2017;28(suppl_5):v295–v329.
  • Koshkin VS, O’Donnell P, Yu EY, et al. Systematic review: targeting HER2 in bladder cancer. Bladder Cancer. 2018;5(1):1–12.
  • Hussain MH, MacVicar GR, Petrylak DP, et al. Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II national cancer institute trial. J Clin Oncol. 2007;25(16):2218–2224.
  • Felsenstein KM, Theodorescu D. Precision medicine for urothelial bladder cancer: update on tumour genomics and immunotherapy. Nat Rev Urol. 2018;15(2):92–111.
  • Kim J, Fox C, Peng S, et al. Preexisting oncogenic events impact trastuzumab sensitivity in ERBB2-amplified gastroesophageal adenocarcinoma. J Clin Invest. 2014;124(12):5145–5158.
  • Bryce AH, Kurzrock R, Meric-Bernstam F, et al. Pertuzumab plus trastuzumab for HER2-positive metastatic urothelial cancer (mUC): preliminary data from mypathway. J Clin Oncol. 2017;35(suppl_6):348.
  • Ross RL, McPherson HR, Kettlewell L, et al. PIK3CA dependence and sensitivity to therapeutic targeting in urothelial carcinoma. BMC Cancer. 2016;16(1):553.
  • Millis SZ, Bryant D, Basu G, et al. Molecular profiling of infiltrating urothelial carcinoma of bladder and nonbladder origin. Clin Genitourin Cancer. 2015;13(1):e37–49.
  • Sathe A, Nawroth R. Targeting the PI3K/AKT/mTOR pathway in bladder cancer. Methods Mol Biol. 2018;1655:335–350.
  • Bellmunt J, Werner L, Riester M, et al. Somatic copy number abnormalities (SCNAs) and mutations in PI3K/AKT pathway and prognostic significance for overall survival (OS) in platinum-treated locally advanced or metastatic urothelial cancer (UC). J Clin Oncol. 2014;32(4_suppl):358.
  • Cho J, Lee J, Kim J, et al. Loss of tuberous sclerosis complex 2 (TSC2) as a predictive biomarker of response to mTOR inhibitor treatment in patients with hepatocellular carcinoma. Transl Oncol. 2016;9(5):466–471.
  • Kwiatkowski DJ, Choueiri TK, Fay AP, et al. Mutations in TSC1, TSC2, and MTOR are associated with response to rapalogs in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2016;22(10):2445–2452.
  • Milowsky MI, Iyer G, Regazzi AM, et al. Phase II study of everolimus in metastatic urothelial cancer. BJU Int. 2013;112(4):462–470.
  • Iyer G, Hanrahan AJ, Milowsky MI, et al. Genome sequencing identifies a basis for everolimus sensitivity. Science. 2012;338(6104):221.
  • Niegisch G, Retz M, Thalgott M, et al. Second-line treatment of advanced urothelial cancer with paclitaxel and everolimus in a german phase II trial (AUO Trial AB 35/09). Oncology. 2015;89(2):70–78.
  • Nassim R, Mansure JJ, Chevalier S, et al. Combining mTOR inhibition with radiation improves antitumor activity in bladder cancer cells in vitro and in vivo: a novel strategy for treatment. PLoS One. 2013;8(6):e65257.
  • Mazzola CR, Chin J. Targeting the VEGF pathway in metastatic bladder cancer. Expert Opin Investig Drugs. 2015;24(7):913–927.
  • Fus LP, Gornicka B. Role of angiogenesis in urothelial bladder carcinoma. Cent European J Urol. 2016;69(3):258–263.
  • Deniz H, Karakok M, Yagci F, et al. Evaluation of relationship between HIF-1alpha immunoreactivity and stage, grade, angiogenic profile and proliferative index in bladder urothelial carcinomas. Int Urol Nephrol. 2010;42(1):103–107.
  • Fauconnet S, Bernardini S, Lascombe I, et al. Expression analysis of VEGF-A and VEGF-B: relationship with clinicopathological parameters in bladder cancer. Oncol Rep. 2009;21(6):1495–1504.
  • Kopparapu PK, Boorjian SA, Robinson BD, et al. Expression of VEGF and its receptors VEGFR1/VEGFR2 is associated with invasiveness of bladder cancer. Anticancer Res. 2013;33(6):2381–2390.
  • Petrylak DP, de Wit R, Chi KN, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial. Lancet. 2017;390(10109):2266–2277.
  • Bellmunt J, Gonzalez-Larriba JL, Prior C, et al. Phase II study of sunitinib as first-line treatment of urothelial cancer patients ineligible to receive cisplatin-based chemotherapy: baseline interleukin-8 and tumor contrast enhancement as potential predictive factors of activity. Ann Oncol. 2011;22(12):2646–2653.
  • Dreicer R, Li H, Stein M, et al. Phase 2 trial of sorafenib in patients with advanced urothelial cancer: a trial of the eastern cooperative oncology group. Cancer. 2009;115(18):4090–4095.
  • Grivas PD, Daignault S, Tagawa ST, et al. Double-blind, randomized, phase 2 trial of maintenance sunitinib versus placebo after response to chemotherapy in patients with advanced urothelial carcinoma. Cancer. 2014;120(5):692–701.
  • Rini BI, Garrett M, Poland B, et al. Axitinib in metastatic renal cell carcinoma: results of a pharmacokinetic and pharmacodynamic analysis. J Clin Pharmacol. 2013;53(5):491–504.
  • Jain RK, Duda DG, Willett CG, et al. Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol. 2009;6(6):327–338.
  • Winer AG, Motzer RJ, Hakimi AA. Prognostic biomarkers for response to vascular endothelial growth factor-targeted therapy for renal cell carcinoma. Urol Clin North Am. 2016;43(1):95–104.
  • Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917–921.
  • Murai J, Huang SY, Das BB, et al. Trapping of PARP1 and PARP2 by clinical PARP inhibitors. Cancer Res. 2012;72(21):5588–5599.
  • Yu E. From the desk of evan yu: “antibody drug conjugates for urothelial carcinoma, a cool technology with promising results.” UroToday [Internet]. 2018 Apr 02 [cited 2018 Sept 26]. Available from: https://www.urotoday.com/clinical-trials/from-the-editor/103205-antibody-drug-conjugates-or-urothelial-carcinoma-a-cool-technology-with-promising-results.html
  • Rosenberg JE, Srikala S, Zhang J, et al. Updated results from the enfortumab vedotin phase 1 (EV-101) study in patients with metastatic urothelial cancer (mUC). J Clin Oncol. 2018;36(suppl_15):4504.
  • Tagawa ST, Faltas B, Lam E, et al. Sacituzumab govitecan (IMMU-132) for patients with pretreated metastatic urothelial uancer (UC): interim results. Ann Oncol. 2017;28(suppl_5):295–329.
  • Bellmunt J, Powles T, Vogelzang NJ. A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: the future is now. Cancer Treat Rev. 2017;54:58–67.
  • Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017;376(11):1015–1026.
  • National Cancer Institute Staff. FDA alters approved use of two checkpoint inhibitors for bladder cancer 2018. National Cancer Institute [Internet]. 2018 Jul 26. Bethesda (MD): National Institutes of Health; [cited 2018 Aug 18]. Available from: https://www.cancer.gov/news-events/cancer-currents-blog/2018/bladder-cancer-checkpoint-inhibitor-change
  • Powles T, Duran I, van der Heijden MS, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2018;391(10122):748–757.
  • Powles T, Rodriguez-Vida A, Duran I, et al. A phase II study investigating the safety and efficacy of neoadjuvant atezolizumab in muscle invasive bladder cancer (ABACUS). J Clin Oncol. 2018;36(suppl_15):4506.
  • Necchi A, Anichini A, Raggi D, et al. Pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive urothelial bladder carcinoma (PURE-01): an open-;abel, single-arm, phase II study. J Clin Oncol. 2018. DOI:10.1200/JCO.18.01148.
  • Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–128.
  • Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371(23):2189–2199.
  • Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. N Engl J Med. 2017;377(25):2500–2501.
  • Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016;387(10031):1909–1920.
  • Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389(10064):67–76.
  • Galsky MD, Saci A, Szabo PM, et al. Impact of zumor mutation burden on nivolumab efficacy in second-line urothelial carcinoma patients: exploratory analysis of the phase ii checkmate 275 study. Ann Oncol. 2017;28(suppl_5):295–329.
  • Daud AI, Loo K, Pauli ML, et al. Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma. J Clin Invest. 2016;126(9):3447–3452.
  • Sharma P, Shen Y, Wen S, et al. CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc Natl Acad Sci U S A. 2007;104(10):3967–3972.
  • Snyder A, Nathanson T, Funt SA, et al. Contribution of systemic and somatic factors to clinical response and resistance to PD-L1 blockade in urothelial cancer: an exploratory multi-omic analysis. PLoS Med. 2017 May;14(5):e1002309.
  • Plimack ER, Bellmunt J, Gupta S, et al. Pembrolizumab (MK-3475) for advanced urothelial cancer: updated results and biomarker analysis from keynote-012. J Clin Oncol. 2017;33(suppl_15):4502.
  • Funt S, Charen AS, Yusko E, et al. Correlation of peripheral and intratumoral T-cell receptor (TCR) clonality with clinical outcomes in patients with metastatic urothelial cancer (mUC) treated with atezolizumab. J Clin Oncol. 2016;34(suppl_15):3005.
  • Mariathasan S, Turley SJ, Nickles D, et al. TGFbeta attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018;554(7693):544–548.
  • Wang L, Saci A, Szabo PM, et al. EMT- and stroma-related gene expression and resistance to PD-1 blockade in urothelial cancer. Nat Commun. 2018;9(1):3503.
  • Teo MY, Seier K, Ostrovnaya I, et al. Alterations in DNA damage response and repair genes as potential marker of clinical benefit From PD-1/PD-L1 blockade in advanced urothelial cancers. J Clin Oncol. 2018;36(17):1685–1694.
  • Galsky MD, Wang H, Hahn NM, et al. Phase 2 trial of gemcitabine, cisplatin, plus ipilimumab in patients with metastatic urothelial cancer and impact of DNA damage response gene mutations on outcomes. Eur Urol. 2018;73(5):751–759.
  • Iyer G, Audenet F, Middha S, et al. Mismatch repair (MMR) detection in urothelial carxcinoma (UC) and correlation with immune checkpoint blockade (ICB) response. J Clin Oncol. 2017;35(suppl_15):4511.
  • Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (checkmate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017;18(3):312–322.
  • Balar AV, Castellano D, O’Donnell PH, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017;18(11):1483–1492.
  • Parikh M, Chong-Xian P, Beckett L, et al. Combination checkpoint immunotherapy and cytotoxic chemotherapy: further results from a phase Ib/II trial of pembrolizumab and docetaxel or gemcitabine in patients with advanced or metastatic urothelial cancer. J Clin Oncol. 2018;36(suppl_6):525.
  • Castellano D, Duran Martinez I, Rodriguez-Vida A, et al. A phase II study investigating the safety and efficacy of neoadjuvant atezolizumab in muscle invasive bladder cancer (ABACUS). Ann Oncol. 2018;29(suppl_8):viii303–viii331.
  • Gopalakrishnan D, Koshkin VS, Ornstein MC, et al. Immune checkpoint inhibitors in urothelial cancer: recent updates and future outlook. Ther Clin Risk Manag. 2018;14:1019–1040.
  • U.S. Food and Drug Administration. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication. U.S. Food and Drug Administration [Internet]. 2018 May 30 [cited 2018 Dec 12]. Available from: https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm560040.htm
  • American Society of Clinical Oncology. FDA approves larotrectinib for solid tumors with NTRK gene fusions. American Society of Clinical Oncology [Internet]. 2018 Nov 26 [cited 2018 Dec 12]. Available from: https://www.asco.org/advocacy-policy/asco-in-action/fda-approves-larotrectinib-solid-tumors-ntrk-gene-fusions
  • Tsimberidou AM, Hong DS, Wheler JJ, et al. Precision medicine: clinical outcomes including long-term survival according to the pathway targeted and treatment period–the impact study. J Clin Oncol. 2018;36(suppl_18):LBA2553–LBA2553.
  • Massard C, Michiels S, Ferté C, et al. High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: results of the moscato 01 trial. Cancer Discov. 2017;7(6):586–595.
  • Le Tourneau C, Delord JP, Goncalves A, et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (shiva): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol. 2015;16(13):1324–1334.
  • American Society of Clinical Oncology. ASCO expands tapur study enrollment after promising initial treatment outcomes seen. American Society of Clinical Oncology [Internet]. 2017 Nov 16 [cited 2018 Dec 12]. Available from: https://www.asco.org/about-asco/press-center/news-releases/asco-expands-tapur-study-enrollment-after-promising-initial
  • Lee K-H, Song CG. Epigenetic regulation in bladder cancer: development of new prognostic targets and therapeutic implications. Trans Cancer Res. 2017;S677–S688.
  • Grivas P, Mortazavi A, Picus J, et al. Mocetinostat for patients with previously treated, locally advanced/metastatic urothelial carcinoma and inactivating alterations of acetyltransferase genes. Cancer. 2018. DOI:10.1002/cncr.31817.

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