The current state of molecular testing in the treatment of patients with solid tumors, 2019

Wafik S El-Deiry, Richard M Goldberg, Heinz-Josef Lenz, Anthony F Shields, Geoffrey T Gibney, Antoinette R Tan, Jubilee Brown, Burton Eisenberg, Elisabeth I Heath, Surasak Phuphanich, Edward Kim, Andrew J Brenner, John L Marshall, Wafik S El-Deiry, Richard M Goldberg, Heinz-Josef Lenz, Anthony F Shields, Geoffrey T Gibney, Antoinette R Tan, Jubilee Brown, Burton Eisenberg, Elisabeth I Heath, Surasak Phuphanich, Edward Kim, Andrew J Brenner, John L Marshall

Abstract

The world of molecular profiling has undergone revolutionary changes over the last few years as knowledge, technology, and even standard clinical practice have evolved. Broad molecular profiling is now nearly essential for all patients with metastatic solid tumors. New agents have been approved based on molecular testing instead of tumor site of origin. Molecular profiling methodologies have likewise changed such that tests that were performed on patients a few years ago are no longer complete and possibly inaccurate today. As with all rapid change, medical providers can quickly fall behind or struggle to find up-to-date sources to ensure he or she provides optimum care. In this review, the authors provide the current state of the art for molecular profiling/precision medicine, practice standards, and a view into the future ahead.

Keywords: biomarkers; cancer; drug target; gene expression profiling; molecular profiling; molecular-targeted therapy; mutation; precision medicine; sequence analysis.

© 2019 The Authors. CA A Cancer Journal for Clinicians published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Figures

Figure 1
Figure 1
Venn Diagram of the Relationships Between High Tumor Mutational Burden (TMB), High Microsatellite Instability (MSI‐H), and High Programmed Death–Ligand 1 (PD‐L1) for All Cancer Types.10

References

    1. Centers for Medicare & Medicaid Services . CMS finalizes coverage of next generation sequencing tests, ensuring enhanced access for cancer patients [press release]. Baltimore, MD: Centers for Medicare & Medicaid Services; 2018. . Accessed February 6, 2019.
    1. US Food and Drug Administration . FoundationOne CDx‐P170019. Silver Spring, MD: US Food and Drug Administration; 2017. . Accessed February 6, 2019.
    1. Bhuvaneshwar K, Belouali A, Singh V, et al. G‐DOC Plus—an integrative bioinformatics platform for precision medicine. BMC Bioinformatics. 2016;17:193.
    1. Ciardiello F, Adams R, Tabernero J, et al. Awareness, understanding, and adoption of precision medicine to deliver personalized treatment for patients with cancer: a multinational survey comparison of physicians and patients. Oncologist. 2016;21:292‐300.
    1. Verma M. Personalized medicine and cancer. J Pers Med. 2012;2:1‐14.
    1. Juhl H. Preanalytical aspects: a neglected issue. Scand J Clin Lab Invest Suppl. 2010;242:63‐65.
    1. Lange N, Unger F, Schoppler M, Pursche K, Juhl H, David KA. Identification and validation of a potential marker of tissue quality using gene expression analysis of human colorectal tissue. PLoS One. 2015;10:e0133987. doi:10.1371/journal.pone.0133987
    1. Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology. 2010;138:2073‐2087.e3.
    1. Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003;348:919‐932.
    1. Vanderwalde A, Spetzler D, Xiao N, Gatalica Z, Marshall J. Microsatellite instability status determined by next‐generation sequencing and compared with PD‐L1 and tumor mutational burden in 11,348 patients. Cancer Med. 2018;7:746‐756.
    1. Bonneville R, Krook MA, Kautto EA, et al. Landscape of microsatellite instability across 39 cancer types. JCO Precis Oncol. 2017;1:1‐15. doi:10.1200/PO.17.00073
    1. Chang L, Chang M, Kautto HM, et al. Microsatellite instability: a predictive biomarker for cancer immunotherapy. Appl Immunohistochem Mol Morphol. 2018;26:e15‐e21. doi:10.1097/PAI.0000000000000575.
    1. Ott PA, Bang YJ, Berton‐Rigaud D, et al. Safety and antitumor activity of pembrolizumab in advanced programmed death ligand 1-positive endometrial cancer: results from the KEYNOTE-028 Study. J Clin Oncol. 2017;35:2535‐2541.
    1. US Food and Drug Administration . FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication.. Silver Spring, MD: US Food and Drug Administration; 2017. . Accessed February 6, 2019
    1. Pai‐Scherf L, Blumenthal GM, Li H, et al. FDA approval summary: pembrolizumab for treatment of metastatic non-small cell lung cancer: firstline therapy and beyond. Oncologist. 2017;22:1392‐1399.
    1. Broderick JM. FDA Approves Nivolumab/Ipilimumab for MSI‐H/dMMR Colorectal Cancer Wednesday, Jul 11, 2018. .
    1. Overman MJ, Lonardi S, Wong KYM, et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair‐deficient/microsatellite instability‐high metastatic colorectal cancer. J Clin Oncol. 2018;36:773‐779. doi:10.1200/JCO.2017.76.9901
    1. Gatalica Z, Xiu J, Swensen J, Vranic S Molecular characterization of cancers with NTRK gene fusions. Mod Pathol. 2019;32:147‐153.
    1. Planchard D, Smit EF, Groen HJM, et al. Dabrafenib plus trametinib in patients with previously treated BRAF (V600E)‐mutant metastatic non‐small cell lung cancer: an open‐label, multicentre phase 2 trial. Lancet Oncol. 2017;18:1307‐1316.
    1. Li BT, Shen R, Buonocore D, et al. Ado‐trastuzumab emtansine in patients with HER2‐mutant lung cancers: results from a phase II basket trial. J Clin Oncol. 2018;36:2532‐2537.
    1. Paik PK, Drilon A, Fan PD, et al. Response to MET inhibitors in patients with stage IV lung adenocarcinomas harboring MET mutations causing exon 14 skipping. Cancer Discov. 2015;5:842‐849. doi:10.1158/-14-1467
    1. Lee SH, Lee JK, Ahn MJ, et al. Vandetanib in pretreated patients with advanced non‐small cell lung cancer‐harboring RET rearrangement: a phase II clinical trial. Ann Oncol. 2017;28:292‐297.
    1. Drilon A, Rekhtman N, Arcila M, et al. Cabozantinib in patients with advanced RET‐rearranged non‐small‐cell lung cancer: an open‐label, single‐centre, phase 2, single‐arm trial. Lancet Oncol. 2016;17:1653‐1660.
    1. Lindeman NI, Cagle PT, Aisner DL, et al. Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. J Mol Diagn. 2018;20:129‐159.
    1. Fuse MJ, Okada K, Oh‐Hara T, Ogura H, Fujita N, Katayama R. Mechanisms of resistance to NTRK inhibitors and therapeutic strategies in NTRK1‐rearranged cancers. Mol Cancer Ther. 2017;16:2130‐2143.
    1. US Food and Drug Administration . FDA approves larotrectinib for solid tumors with NTRK gene fusions. Silver Spring, MD: US Food and Drug Administration; 2018. . Accessed February 6, 2019.
    1. Drilon A, De Braud FG, Siena S, et al. Entrectinib, an oral pan‐Trk, ROS1, and ALK inhibitor in TKI‐naïve patients with advanced solid tumors harboring gene rearrangements. Presented at: The 2016 AACR Annual Meeting; April 16‐20, 2016; New Orleans, LA. Abstract CT007.
    1. FDA Grants Entrectinib Breakthrough Designation for NTRK+ Solid Tumors. Published: Tuesday, Accessed May 16, 2017
    1. Hechtman JF, Benayed R, Hyman DM, et al. Pan‐Trk immunohistochemistry is an efficient and reliable screen for the detection of NTRK fusions. Am J Surg Pathol. 2017;41:1547‐1551.
    1. Hung YP, Fletcher CDM, Hornick JL. Evaluation of pan‐TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis‐like neural tumour and histological mimics. Histopathology. 2018;73:634‐644.
    1. Murphy DA, Ely HA, Shoemaker R, et al. Detecting gene rearrangements in patient populations through a 2‐step diagnostic test comprised of rapid IHC enrichment followed by sensitive next‐generation sequencing. Appl Immunohistochem Mol Morphol. 2017;25:513‐523.
    1. Lartigue J. Blurring the lines between germline and somatic mutations in cancer. Oncol Live. 2017;18 . Accessed February 6, 2019.
    1. Ding L, Getz G, Wheeler DA, et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature. 2008;455:1069‐1075.
    1. Yurgelun MB, Kulke MH, Fuchs CS, et al. Cancer susceptibility gene mutations in individuals with colorectal cancer. J Clin Oncol. 2017;35:1086‐1095.
    1. Waddell N, Pajic M, Patch AM, et al. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature. 2015;518:495‐501.
    1. Schrader KA, Cheng DT, Joseph V, et al. Germline variants in targeted tumor sequencing using matched normal DNA. JAMA Oncol. 2016;2:104‐111.
    1. Sinicrope FA, Sargent DJ. Clinical implications of microsatellite instability in sporadic colon cancers. Curr Opin Oncol. 2009;21:369‐373.
    1. Ribic CM, Sargent DJ, Moore MJ, et al. Tumor microsatellite‐instability status as a predictor of benefit from fluorouracil‐based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003;349:247‐257.
    1. Sargent DJ, Marsoni S, Monges G, et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil‐based adjuvant therapy in colon cancer. J Clin Oncol. 2010;28:3219‐3226.
    1. Sinicrope FA, Foster NR, Thibodeau SN, et al. DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5‐fluorouracil‐based adjuvant therapy. J Natl Cancer Inst. 2011;103:863‐875.
    1. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group . Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Genet Med. 2009;11:35‐41.
    1. Fuchs CS, Doi T, Jang RWJ, et al. KEYNOTE‐059 cohort 1: efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer [abstract]. J Clin Oncol. 2017;35(15 suppl):4003.
    1. Burn J, Gerdes AM, Macrae F, et al. Long‐term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet. 2009;378:2081‐2087.
    1. Liao X, Lochhead P, Nishihara R, et al. Aspirin use, tumor PIK3CA mutation, and colorectal‐cancer survival. N Engl J Med. 2012;367:1596‐1606.
    1. Karnoub AE, Weinberg RA. Ras oncogenes: split personalities. Nat Rev Mol Cell Biol. 2008;9:517‐531.
    1. Di Nicolantonio F, Martini M, Molinari F, et al. Wild‐type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008;26:5705‐5712.
    1. Passiglia F, Bronte G, Bazan V, Galvano A, Vincenzi B, Russo A. Can KRAS and BRAF mutations limit the benefit of liver resection in metastatic colorectal cancer patients? A systematic review and meta‐analysis. Crit Rev Oncol Hematol. 2018;99:150‐157.
    1. Richman SD, Seymour MT, Chambers P, et al. KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial. J Clin Oncol. 2009;27:5931‐5937.
    1. Roth AD, Tejpar S, Delorenzi M, et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC‐3, EORTC 40993, SAKK 60‐00 trial. J Clin Oncol. 2010;28:466‐474.
    1. Schirripa M, Bergamo F, Cremolini C, et al. BRAF and RAS mutations as prognostic factors in metastatic colorectal cancer patients undergoing liver resection. Br J Cancer. 2015;112:1921‐1928.
    1. Sinicrope FA, Shi Q, Smyrk TC, et al. Molecular markers identify subtypes of stage III colon cancer associated with patient outcomes. Gastroenterology. 2015;148:88‐99.
    1. Van Cutsem E, Kohne CH, Lang I, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first‐line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011;29:2011‐2019.
    1. Carter J, Tseng LH, Zheng G, et al. Non‐p.V600E BRAF mutations are common using a more sensitive and broad detection tool. Am J Clin Pathol. 2015;144:620‐628.
    1. Tran B, Kopetz S, Tie J, et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer. 2011;117:4623‐4632.
    1. Robertson AG, Kim J, Al‐Ahmadie H, et al. Comprehensive molecular characterization of muscle‐invasive bladder cancer. Cell. 2017;171:540‐556, e525.
    1. 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. 2019;25:977‐988. doi:10.1158/1078-0432.CCR-18-1001
    1. Van Allen EM, Mouw KW, Kim P, et al. Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle‐invasive urothelial carcinoma. Cancer Discov. 2014;4:1140‐1153.
    1. Antonarakis ES, Lu C, Luber B, et al. Germline DNA‐repair gene mutations and outcomes in men with metastatic castration‐resistant prostate cancer receiving first‐line abiraterone and enzalutamide. Eur Urol. 2018;74:218‐225.
    1. Lu E, Thomas GV, Chen Y, et al. DNA repair gene alterations and PARP inhibitor response in patients with metastatic castration‐resistant prostate cancer. J Natl Compr Canc Netw. 2018;16:933‐937.
    1. De Bono JS, Goh JCH, Ojamaa K, et al. KEYNOTE‐199: pembrolizumab (pembro) for docetaxel‐refractory metastatic castration‐resistant prostate cancer (mCRPC) [abstract]. J Clin Oncol. 2018;36(15 suppl):5007.
    1. Carroll PR, Parsons JK, Andriole G, et al. NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016. J Natl Compr Canc Netw. 2016;14:509‐519.
    1. Society of Gynecologic Oncology (SGO) . SOG Clinical Practice Statement: Screening for Lynch Syndrome in Endometrial Cancer. Chicago, IL: Society of Gynecologic Oncology; 2014. . Accessed February 6, 2019.
    1. Na R, Zheng SL, Han M, et al. Germline mutations in ATM and BRCA1/2 distinguish risk for lethal and indolent prostate cancer and are associated with early age at death. Eur Urol. 2017;71:740‐747.
    1. Slomovitz BM, Jiang Y, Yates MS, et al. Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma. J Clin Oncol. 2015;33:930‐936.
    1. Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinum‐sensitive, recurrent ovarian cancer. N Engl J Med. 2016;375:2154‐2164.
    1. Coleman RL, Oza AM, Lorusso D, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double‐blind, placebo‐controlled, phase 3 trial. Lancet. 2017;390:1949‐1961.
    1. Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in platinum‐sensitive relapsed ovarian cancer. N Engl J Med. 2012;366:1382‐1392.
    1. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;27:2495‐2505. doi:10.1056/NEJMoa1810858
    1. Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473‐2483.
    1. Oza AM, Cook AD, Pfisterer J, et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015;16:928‐936.
    1. Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in patients with platinum‐sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014;15:852‐861.
    1. Niemeier LA, Dabbs DJ, Beriwal S, Striebel JM, Bhargava R. Androgen receptor in breast cancer: expression in estrogen receptor‐positive tumors and in estrogen receptor‐negative tumors with apocrine differentiation. Mod Pathol. 2010;23:205‐212.
    1. Gucalp A, Tolaney S, Isakoff SJ, et al. Phase II trial of bicalutamide in patients with androgen receptor‐positive, estrogen receptor‐negative metastatic breast cancer. Clin Cancer Res. 2013;19:5505‐5512.
    1. Schiavon G, Hrebien S, Garcia‐Murillas I, et al. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci Transl Med. 2015;7:313ra182.
    1. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131:803‐820.
    1. Stupp R, Brada M, van den Bent MJ, Tonn JC, Pentheroudakis G; ESMO Guidelines Working Group . High‐grade glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow‐up. Ann Oncol. 2014;25(suppl_3):iii93‐iii101.
    1. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO Classification of Tumours of the Central Nervous System. Acta Neuropathol. 2007;114:97‐109.
    1. Donahue B, Scott CB, Nelson JS, et al. Influence of an oligodendroglial component on the survival of patients with anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83‐02. Int J Radiat Oncol Biol Phys. 1997;38:911‐914.
    1. van den Bent MJ. Interobserver variation of the histopathological diagnosis in clinical trials on glioma: a clinician's perspective. Acta Neuropathol. 2010;120:297‐304.
    1. Ramkissoon SH, Bi WL, Schumacher SE, et al. Clinical implementation of integrated whole‐genome copy number and mutation profiling for glioblastoma. Neuro Oncol. 2015;17:1344‐1355.
    1. Tabone T, Abuhusain HJ, Nowak AK, Erber WN, McDonald KL. Multigene profiling to identify alternative treatment options for glioblastoma: a pilot study. J Clin Pathol. 2014;67:550‐555.
    1. Blumenthal DT, Dvir A, Lossos A, et al. Clinical utility and treatment outcome of comprehensive genomic profiling in high grade glioma patients. J Neurooncol. 2016;130:211‐219.
    1. Cook PJ, Thomas R, Kannan R, et al. Somatic chromosomal engineering identifies BCAN‐NTRK1 as a potent glioma driver and therapeutic target. Nat Commun. 2017;8:15987.
    1. Alvarez‐Breckenridge C, Miller JJ, Nayyar N, et al. Clinical and radiographic response following targeting of BCAN‐NTRK1 fusion in glioneuronal tumor. NPJ Precis Oncol. 2017;1:5.
    1. Lassaletta A, Zapotocky M, Mistry M, et al. Therapeutic and prognostic implications of BRAF V600E in pediatric low‐grade gliomas. J Clin Oncol. 2017;35:2934‐2941.
    1. Dabrafenib effective in pediatric glioma. Cancer Discov. 2017;7:OF5.
    1. van den Bent M, Gan HK, Lassman AB, et al. Efficacy of depatuxizumab mafodotin (ABT‐414) monotherapy in patients with EGFR‐amplified, recurrent glioblastoma: results from a multi‐center, international study. Cancer Chemother Pharmacol. 2017;80:1209‐1217.
    1. Reardon DA, Lassman AB, van den Bent M, et al. Efficacy and safety results of ABT‐414 in combination with radiation and temozolomide in newly diagnosed glioblastoma. Neuro Oncol. 2017;19:965‐975.
    1. Lassman AB, van den Bent MJ, Gan HK, et al. Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with EGFR‐amplified, recurrent glioblastoma: results from an international phase I multicenter trial. Neuro Oncol. 2019;21:106‐114. doi:10.1093/neuonc/noy091
    1. Schindler G, Capper D, Meyer J, et al. Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra‐cerebellar pilocytic astrocytoma. Acta Neuropathol. 2011;121:397‐405.
    1. US Food and Drug Administration . Nivolumab for SCCHN. Silver Spring, MD: US Food and Drug Administration; 2016. . Accessed February 6, 2019.
    1. US Food and Drug Administration . Pembrolizumab (KEYTRUDA). Silver Spring, MD: US Food and Drug Administration; 2016. . Accessed February 6, 2019.
    1. Agarwal V, Subash A, Nayar R‐C, Rao V. Is EGFR really a therapeutic target in head and neck cancers?. J Surg Oncol. 2019;119:685‐686. doi:10.1002/jso.25386
    1. Wheeler DL, Dunn EF, Harari PM. Understanding resistance to EGFR inhibitors‐impact on future treatment strategies. Nat Rev Clin Oncol. 2010;7:493‐507.
    1. Blaszczak W, Barczak W, Wegner A, Golusinski W, Suchorska WM. Clinical value of monoclonal antibodies and tyrosine kinase inhibitors in the treatment of head and neck squamous cell carcinoma. Med Oncol. 2017;34:60.
    1. Jung K, Kang H, Mehra R. Targeting phosphoinositide 3‐kinase (PI3K) in head and neck squamous cell carcinoma (HNSCC). Cancers Head Neck. 2018;3:3.
    1. Kobayashi K, Hisamatsu K, Suzui N, Hara A, Tomita H, Miyazaki T. A review of HPV‐related head and neck cancer. J Clin Med. 2018;7:E241.
    1. Salama AK, Flaherty KT. BRAF in melanoma: current strategies and future directions. Clin Cancer Res. 2013;19:4326‐4334.
    1. Gibney GT, Messina JL, Fedorenko IV, Sondak VK, Smalley KS. Paradoxical oncogenesis—the long‐term effects of BRAF inhibition in melanoma. Nat Rev Clin Oncol. 2013;10:390‐399.
    1. Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF‐mutated melanoma. N Engl J Med. 2017;377:1813‐1823.
    1. Long GV, Flaherty KT, Stroyakovskiy D, et al. Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K‐mutant melanoma: long‐term survival and safety analysis of a phase 3 study. Ann Oncol. 2017;28:1631‐1639.
    1. Beadling C, Jacobson‐Dunlop E, Hodi FS, et al. KIT gene mutations and copy number in melanoma subtypes. Clin Cancer Res. 2008;14:6821‐6828.
    1. Bastian BC, Esteve‐Puig R. Targeting activated KIT signaling for melanoma therapy. J Clin Oncol. 2013;31:3288‐3290.
    1. Guo J, Si L, Kong Y, et al. Phase II, open‐label, single‐arm trial of imatinib mesylate in patients with metastatic melanoma harboring c‐Kit mutation or amplification. J Clin Oncol. 2011;29:2904‐2909.
    1. Carvajal RD, Antonescu CR, Wolchok JD, et al. KIT as a therapeutic target in metastatic melanoma. JAMA. 2011;305:2327‐2334.
    1. Hodi FS, Corless CL, Giobbie‐Hurder A, et al. Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun‐damaged skin. J Clin Oncol. 2013;31:3182‐3190.
    1. Fedorenko IV, Gibney GT, Smalley KSM. NRAS mutant melanoma: biological behavior and future strategies for therapeutic management. Oncogene. 2017;32:3009‐3018.
    1. Dummer R, Schadendorf D, Ascierto PA, et al. Binimetinib versus dacarbazine in patients with advanced NRAS‐mutant melanoma (NEMO): a multicentre, open‐label, randomised, phase 3 trial. Lancet Oncol. 2017;18:435‐445.
    1. Gibney GT, Weiner LM, Atkins MB. Predictive biomarkers for checkpoint inhibitor‐based immunotherapy. Lancet Oncol. 2016;17:e542‐e551.
    1. Johnson DB, Frampton GM, Rioth MJ, et al. Targeted next generation sequencing identifies markers of response to PD‐1 blockade. Cancer Immunol Res. 2016;4:959‐967.
    1. Hodi FS, Chiarion‐Sileni V, Gonzalez R, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4‐year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol. 2018;19:1480‐1492.
    1. Gianni L, Dafni U, Gelber RD, et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2‐positive early breast cancer: a 4‐year follow‐up of a randomised controlled trial. Lancet Oncol. 2011;12:236‐244.
    1. Baselga J, Bradbury I, Eidtmann H, et al. Lapatinib with trastuzumab for HER2‐positive early breast cancer (NeoALTTO): a randomised, open‐label, multicentre, phase 3 trial. Lancet. 2012;379:633‐640.
    1. McNeil C. NCI‐MATCH launch highlights new trial design in precision‐medicine era. J Natl Cancer Inst. 2015;107:djv193.
    1. Mangat PK, Halabi S, Bruinooge SS, et al. Rationale and design of the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. JCO Precis Oncol. 2018;2018. doi:10.1200/PO.18.00122
    1. Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20:1467‐1473.
    1. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non‐Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059‐3068.
    1. Lister TA, Crowther D, Sutcliffe SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol. 1989;7:1630‐1636.
    1. European Organization for Research and Treatment of Cancer (EORTC) . SPECTA (Screening Patients for Efficient Clinical Trial Access). Recent Developments of the EORTC Collaborative Program Towards Precision Medicine. . Accessed February 6, 2019.
    1. Lacombe D, Tejpar S, Salgado R, et al. European perspective for effective cancer drug development. Nat Rev Clin Oncol. 2014;11:492‐498.
    1. European Organization for Research and Treatment of Cancer . The European Organization for Research and Treatment of Cancer Screening Patients for Efficient Clinical Trial Access (EORTC‐SPECTA) program. . Accessed February 6, 2019.
    1. Yao S, Zhu Y, Chen L. Advances in targeting cell surface signalling molecules for immune modulation. Nat Rev Drug Discov. 2013;12:130‐146.
    1. Chen DS, Mellman I. Oncology meets immunology: the cancer‐immunity cycle. Immunity. 2013;39:1‐10.
    1. Patel SP, Kurzrock R. PD‐L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14:847‐856.
    1. Mahoney KM, Atkins MB. Prognostic and predictive markers for the new immunotherapies. Oncology (Williston Park). 2014;28(suppl 3):39‐48.
    1. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non‐small‐cell lung cancer. N Engl J Med. 2015;372:2018‐2028.
    1. Reck M, Rodriguez‐Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD‐L1‐positive non‐small‐cell lung cancer. N Engl J Med. 2016;375:1823‐1833.
    1. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD‐L1‐positive, advanced non‐small‐cell lung cancer (KEYNOTE‐010): a randomised controlled trial. Lancet. 2016;387:1540‐1550.
    1. Borghaei H, Paz‐Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non‐small‐cell lung cancer. N Engl J Med. 2015;373:1627‐1639.
    1. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous‐cell non‐small‐cell lung cancer. N Engl J Med. 2015;373:123‐135.
    1. Mansfield AS, Murphy SJ, Peikert T, et al. Heterogeneity of programmed cell death ligand 1 expression in multifocal lung cancer. Clin Cancer Res. 2016;22:2177‐2182.
    1. Chen J, Jiang CC, Jin L, Zhang XD. Regulation of PD‐L1: a novel role of pro‐survival signalling in cancer. Ann Oncol. 2016;27:409‐416.
    1. Hirsch FR, McElhinny A, Stanforth D, et al. PD‐L1 immunohistochemistry assays for lung cancer: results from phase 1 of the Blueprint PD‐L1 IHC Assay Comparison Project. J Thorac Oncol. 2017;12:208‐222.
    1. Rimm DL, Han G, Taube JM, et al. A prospective, multi‐institutional, pathologist‐based assessment of 4 immunohistochemistry assays for PD‐L1 expression in non‐small cell lung cancer. JAMA Oncol. 2017;3:1051‐1058.
    1. Alexandrov LB, Nik‐Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500:415‐421.
    1. Champiat S, Ferte C, Lebel‐Binay S, Eggermont A, Soria JC. Exomics and immunogenics: bridging mutational load and immune checkpoints efficacy. Oncoimmunology. 2014;3:e27817.
    1. Zibelman M, Ramamurthy C, Plimack ER. Emerging role of immunotherapy in urothelial carcinoma—advanced disease. Urol Oncol. 2016;34:538‐547.
    1. Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA‐4 blockade in melanoma. N Engl J Med. 2014;371:2189‐2199.
    1. Van Allen EM, Miao D, Schilling B, et al. Genomic correlates of response to CTLA‐4 blockade in metastatic melanoma. Science. 2015;350:207‐211.
    1. 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;348:124‐128.
    1. Le DT, Uram JN, Wang H, et al. PD‐1 blockade in tumors with mismatch‐repair deficiency. N Engl J Med. 2015;372:2509‐2520.
    1. Miao D, Margolis CA, Gao W, et al. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science. 2018;359:801‐806. doi:10.1126/science.aan5951
    1. Helleday T. Homologous recombination in cancer development, treatment and development of drug resistance. Carcinogenesis. 2010;31:955‐960.
    1. Li X, Heyer WD. Homologous recombination in DNA repair and DNA damage tolerance. Cell Res. 2008;18:99‐113.
    1. Lord CJ, Ashworth A. BRCAness revisited. Nat Rev Cancer. 2016;16:110‐120.
    1. Krejci L, Altmannova V, Spirek M, Zhao X. Homologous recombination and its regulation. Nucleic Acids Res. 2012;40:5795‐5818.
    1. Turner N, Tutt A, Ashworth A. Hallmarks of 'BRCAness' in sporadic cancers. Nat Rev Cancer. 2004;4:814‐819.
    1. Silver DP, Livingston DM. Mechanisms of BRCA1 tumor suppression. Cancer Discov. 2012;2:679‐684.
    1. Watkins JA, Irshad S, Grigoriadis A, Tutt AN. Genomic scars as biomarkers of homologous recombination deficiency and drug response in breast and ovarian cancers. Breast Cancer Res. 2014;16:211.
    1. Antoniou AC, Foulkes WD, Tischkowitz M. Breast‐cancer risk in families with mutations in PALB2. N Engl J Med. 2014;371:1651‐1652.
    1. Antoniou AC, Casadei S, Heikkinen T, et al. Breast‐cancer risk in families with mutations in PALB2. N Engl J Med. 2014;371:497‐506.
    1. Song H, Dicks E, Ramus SJ, et al. Contribution of germline mutations in the RAD51B, RAD51C, and RAD51D genes to ovarian cancer in the population. J Clin Oncol. 2015;33:2901‐2907.
    1. Ramus SJ, Song H, Dicks E, et al. Germline mutations in the BRIP1, BARD1, PALB2, and NBN genes in women with ovarian cancer. J Natl Cancer Inst. 2015;107:djv214.
    1. den Brok WD, Schrader KA, Sun S, et al. Homologous recombination deficiency in breast cancer: a clinical review. JCO Precis Oncol. 2016;2017. doi:10.1200/PO.16.00031
    1. Moschetta M, George A, Kaye SB, Banerjee S. BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer. Ann Oncol. 2016;27:1449‐1455.
    1. Hennessy BT, Timms KM, Carey MS, et al. Somatic mutations in BRCA1 and BRCA2 could expand the number of patients that benefit from poly (ADP ribose) polymerase inhibitors in ovarian cancer. J Clin Oncol. 2010;28:3570‐3576.
    1. McCabe N, Turner NC, Lord CJ, et al. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP‐ribose) polymerase inhibition. Cancer Res. 2006;66:8109‐8115.
    1. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917‐921.
    1. Gatalica Z, Xiu J, Swensen J, Vranic S. Molecular characterization of cancers with NTRK gene fusions. Mod Pathol. 2019;32:147‐153.
    1. Loriot Y, Necchi A, Park SE, et al. Erdafitinib (ERDA; JNJ‐42756493), a pan‐fibroblast growth factor receptor (FGFR) inhibitor, in patients with metastatic or unresectable urothelial carcinoma (mUC) and FGFR alterations: phase 2 continuous versus intermittent dosing [abstract]. J Clin Oncol. 2018;36(6 suppl):411.
    1. Chae YK, Vaklavas C, Cheng HH, et al. Molecular Analysis for Therapy Choice (MATCH) arm W: phase II study of AZD4547 in patients with tumors with aberrations in the FGFR pathway [abstract]. J Clin Oncol. 2018;36(15 suppl):2503.
    1. Kawakami H, Okamoto I, Okamoto W, Tanizaki J, Nakagawa K, Nishio K. Targeting MET amplification as a new oncogenic driver. Cancers (Basel). 2014;6:1540‐1552.
    1. Camidge DR, Otterson GA, Clark JW, et al. Crizotinib in patients (pts) with MET‐amplified non‐small cell lung cancer (NSCLC): updated safety and efficacy findings from a phase 1 trial [abstract]. J Clin Oncol. 2018;36(15 suppl):9062.
    1. Burris HA 3rd, Kurkjian CD, Hart L, et al. AK‐228 (formerly MLN0128), an investigational dual TORC1/2 inhibitor plus paclitaxel, with/without trastuzumab, in patients with advanced solid malignancies. Cancer Chemother Pharmacol. 2017;80:261‐273.
    1. Krop IE, Jegede O, Grilley‐Olson E, et al. Results from molecular analysis for therapy choice (MATCH) arm I: taselisib for PIK3CA‐mutated tumors [abstract]. J Clin Oncol. 2018;36(15 suppl):101.
    1. US Food and Drug Administration . Palbociclib (IBRANCE). Silver Spring, MD: US Food and Drug Administration; 2017. . Accessed February 6, 2019.
    1. Al Baghdadi T, Halabi S, Garrett‐Mayer E, et al. Palbociclib (P) in patients (Pts) with pancreatic cancer (PC) and gallbladder or bile duct cancer (GBC) with CDKN2A alterations: results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study [abstract]. J Clin Oncol. 2018;36(15 suppl):2532.
    1. Xu C, Buczkowski KA, Zhang Y, et al. NSCLC driven by DDR2 mutation is sensitive to dasatinib and JQ1 combination therapy. Mol Cancer Ther. 2015;14:2382‐2389.
    1. Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early‐ and late‐stage human malignancies. Sci Transl Med. 2014;6:224ra224.
    1. Diaz LA Jr, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol. 2014;32:579‐586.
    1. Domenyuk V, Zhong Z, Stark A, et al. Plasma exosome profiling of cancer patients by a next generation systems biology approach. Sci Rep. 2017;7:42717. doi:10.1038/srep42741
    1. Domenyuk V, Gatalica Z, Santhanam R, et al. Poly‐ligand profiling differentiates trastuzumab‐treated breast cancer patients according to their outcomes. Nat Commun. 2018;9:1219.
    1. Aziz N, Zhao Q, Bry L, et al. College of American Pathologists' laboratory standards for next‐generation sequencing clinical tests. Arch Pathol Lab Med. 2015;139:481‐493.
    1. Gargis AS, Kalman L, Berry MW, et al. Assuring the quality of next‐generation sequencing in clinical laboratory practice. Nat Biotechnol. 2012;30:1033‐1036.
    1. Jennings LJ, Arcila ME, Corless C, et al. Guidelines for validation of next‐generation‐sequencing‐based oncology panels. J Mol Diagn. 2017;19:341‐365.
    1. Schrijver I, Aziz N, Farkas DH, et al. Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology. J Mol Diagn. 2012;14:525‐540.
    1. Sims DJ, Harrington RD, Polley EC, et al. Plasmid‐based materials as multiplex quality controls and calibrators for clinical next‐generation sequencing assays. J Mol Diagn. 2016;18:336‐349.
    1. Gerlinger M, Rowan AJ, Horswell S, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366:883‐892.
    1. Thierry AR, Pastor B, Jiang ZQ, et al. Circulating DNA demonstrates convergent evolution and common resistance mechanisms during treatment of colorectal cancer. Clin Cancer Res. 2017;23:4578‐4591.

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