Up-and-Coming Experimental Drug Options for Metastatic Colorectal Cancer

References

• National Cancer Institute. Cancer stat facts: colorectal cancer SEER data. Available from: https://seer.cancer.gov/statfacts/html/colorect.html. Accessed September 29, 2020.
   Google Scholar
• Riihimaki M, Hemminki A, Sundquist J, Hemminki K. Patterns of metastasis in colon and rectal cancer. Sci Rep. 2016;6:29765. doi:10.1038/srep29765
   PubMed Web of Science ®Google Scholar
• Li J, Zhao X, Chen L, et al. Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies. BMC Cancer. 2010;10:529. doi:10.1186/1471-2407-10-529
   PubMed Web of Science ®Google Scholar
• Tian S, Quan H, Xie C, et al. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci. 2011;102(7):1374–1380. doi:10.1111/j.1349-7006.2011.01939.x
   PubMed Web of Science ®Google Scholar
• Bogenrieder T, Herlyn M. Axis of evil: molecular mechanisms of cancer metastasis. Oncogene. 2003;22:6524–6536. doi:10.1038/sj.onc.1206757
   PubMed Web of Science ®Google Scholar
• Bendardaf R, Buhmeida A, Hilska M, et al. VEGF-1 expression in colorectal cancer is associated with disease localization, stage, and long-term disease-specific survival. Anticancer Res. 2008;28:3865–3870.
   PubMed Web of Science ®Google Scholar
• Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335–2342. doi:10.1056/NEJMoa032691
   PubMed Web of Science ®Google Scholar
• Tabernero J, Yoshino T, Cohn AL, et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomized, double-blind, multicenter, Phase 3 study. Lancet Oncol. 2015;16:499–508.
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Tabernero J, Lakomy R, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol. 2012;30(28):2499–2506.
   Web of Science ®Google Scholar
• Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicenter, randomized, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303–312.
   PubMed Web of Science ®Google Scholar
• Cidon EU, Alonso P, Masters B. Markers of response to antiangiogenic therapies in colorectal cancer: where are we now and what should be next? Clin Med Insights Oncol. 2016;10(S1):41–55.
   Google Scholar
• Rossini D, Moretto CC, Cremolini C, et al. Treatments (tx) after progression to first-line FOLFOXIRI plus bevacizumab (bev) in metastatic colorectal cancer (mCRC) patients (pts): A pooled analysis of TRIBE and MOMA studies by GONO group. J Clin Oncology. 2017;35(15):Abstract 3542. doi:10.1200/JCO.2017.35.15_suppl.3542
   Web of Science ®Google Scholar
• Wang F, Yuan X, Jia J, et al. Apatinib monotherapy for chemotherapy-refractory metastatic colorectal cancer: a multi-centre, single-arm, prospective study. Sci Rep. 2020;10:6058. doi:10.1038/s41598-020-62961-5
   Web of Science ®Google Scholar
• Liang L, Wang L, Zhu P, et al. A pilot study of apatinib as third-line treatment in patients with heavily treated metastatic colorectal cancer. Clinical Colorectal Cancer Gastrointestinal Malignancies. 2018;17(3):E443E449. doi:10.1016/j.clcc.2018.02.011
   Web of Science ®Google Scholar
• Gou M, Haiyan S, Zhang Y, et al. Efficacy and safety of apatinib in patients with previously treated metastatic colorectal cancer: a real-world retrospective study. Sci Rep. 2018;8:4602. doi:10.1038/s41598-018-22302-z
   Web of Science ®Google Scholar
• Li A, Wang K, Xu A, et al. Apatinib as an optional treatment in metastatic colorectal cancer. Medicine. 2019;98(35):e16919. doi:10.1097/MD.0000000000016919
   Web of Science ®Google Scholar
• Cao J, Zhang J, Peng W, et al. A phase I study of safety and pharmacokinetics of fruquintinib, a novel selective inhibitor of vascular endothelial growth factor receptor-1, −2, and −3 tyrosine kinases in Chinese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016;78:259–269. doi:10.1007/s00280-016-3069-8
   PubMed Web of Science ®Google Scholar
• Li J, Qin S, Xu R, et al. Effect of fruquintinib vs placebo on overall survival in patients with previously treated metastatic colorectal cancer the FRESCO randomized clinical trial. JAMA. 2018;319(24):2486–2496.
   PubMed Web of Science ®Google Scholar
• Li X, Giu M, Wang S, et al. A Phase I dose‑escalation, pharmacokinetics and food‑effect study of oral donafenib in patients with advanced solid tumours. Cancer Chemother Pharmacol. 2020;85:593–604. doi:10.1007/s00280-020-04031-1
   PubMed Web of Science ®Google Scholar
• Seshacharyulu P, Ponnusamy MP, Haridas D, et al. Targeting the EGFR signaling pathway in cancer. Expert Opin Ther Targets. 2012;16(1):15–31. doi:10.1517/14728222.2011.648617
   PubMed Web of Science ®Google Scholar
• Xie Y, Chen Y, Fang J. Comprehensive review of targeted therapy for colorectal cancer. Signal Transduction Targeted Therapy. 2020;5:22.
   PubMed Web of Science ®Google Scholar
• Bylsma LC, Gillezeau C, Garawin TA, et al. Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: A systematic review and meta‐analysis. Cancer Med. 2020;9(3):1044–1057. doi:10.1002/cam4.2747
   Web of Science ®Google Scholar
• Van Cutsem E, Köhne C, Láng 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(15):2011–2019. doi:10.1200/JCO.2010.33.5091
   PubMed Web of Science ®Google Scholar
• Vectibix^® (Panitumumab) Injection for Intravenous Use [Package Insert]. Amgen Inc; 2017.
   Google Scholar
• Erbitux^® (Cetuximab) Injection, for Intravenous Use [Package Insert]. Eli Lilly and Company; 2019.
   Google Scholar
• Zhao B, Wang L, Qiu H, et al. Mechanisms of resistance to anti-EGFR therapy in colorectal cancer. Oncotarget. 2017;8(3):3980–4000. doi:10.18632/oncotarget.14012
   PubMedGoogle Scholar
• Li Q, Wang Y, Tu J, et al. Anti-EGFR therapy in metastatic colorectal cancer: mechanisms and potential regimens of drug resistance. Gastroenterology Report. 2020;8(3):179–191. doi:10.1093/gastro/goaa026
   PubMed Web of Science ®Google Scholar
• Bendell JC, Javie M, Bekaii-Saab TS, et al. A Phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. Br J Cancer. 2017;116(5):575–583.
   PubMed Web of Science ®Google Scholar
• Cox AD, Fesik SW, Kimmelman AC, et al. Drugging the undruggable Ras: mission possible? Nat Rev Drug Discov. 2014;13(11):828–851.
   PubMed Web of Science ®Google Scholar
• Schirripa M, Nappo F, Cremolini C, et al. KRAS G12C metastatic colorectal cancer: specific features of a new emerging target population. Clin Colorectal Cancer. 2020;19(3):219–225. doi:10.1016/j.clcc.2020.04.009
   Web of Science ®Google Scholar
• Hong DS, Fakih MG, Strickler JH, et al. KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med. 2020;383:1207–1217. doi:10.1056/NEJMoa1917239
   PubMed Web of Science ®Google Scholar
• Fakih M, Desai J, Kuboki Y, et al. CodeBreak 100: activity of AMG 510, a novel small molecule inhibitor of KRASG12C, in patients with advanced colorectal cancer. J Clinical Oncology. 2020;38(15):4018. doi:10.1200/JCO.2020.38.15_suppl.4018
   Web of Science ®Google Scholar
• Amodio V, Yaeger R, Archella P, et al. EGFR blockade reverts resistance to KRAS G12C inhibition in colorectal cancer. Cancer Discov. 2020;10:1129–1139. doi:10.1158/2159-8290.CD-20-0187
   PubMed Web of Science ®Google Scholar
• Corcoran RB, Atreya CE, Falchook GS, et al. Combined BRAF and MEK inhibition with dabrafenib and trametinib in BRAF V600–mutant colorectal cancer. J Clinical Oncology. 2015;33(34):4023–4031. doi:10.1200/JCO.2015.63.2471
   PubMed Web of Science ®Google Scholar
• Kopetz S, Grothey A, Yaeger R, et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E–mutated colorectal cancer. N Engl J Med. 2019;381:1632–1643. doi:10.1056/NEJMoa1908075
   PubMed Web of Science ®Google Scholar
• Braftovi® (encorafenib) capsules for oral use [Package Insert]. Pfizer Oncology. 2020.
   Google Scholar
• Bennouna J, Lang I, Valladares-Ayerbes M, et al. A Phase II, open-label, randomised study to assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) versus capecitabine monotherapy in patients with colorectal cancer who have failed one or two prior chemotherapeutic regimens. Invest New Drugs. 2011;29:1021–1028. doi:10.1007/s10637-010-9392-8
   PubMed Web of Science ®Google Scholar
• Infante JR, Fecher LA, Falchook GS, et al. Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial. Lancet Oncol. 2012;13(8):773–781. doi:10.1016/S1470-2045(12)70270-X
   PubMed Web of Science ®Google Scholar
• Sullivan RJ, Infante JR, Janku F, et al. First-in-class ERK1/2 inhibitor ulixertinib (BVD-523) in patients with MAPK mutant advanced solid tumors: results of a phase I dose-escalation and expansion study. Cancer Discov. 2018;8(2):184–195. doi:10.1158/2159-8290.CD-17-1119
   PubMed Web of Science ®Google Scholar
• Nowak JA. HER2 in colorectal carcinoma. Surg Pathol Clin. 2020;13(3):485–502. doi:10.1016/j.path.2020.05.007
   PubMedGoogle Scholar
• Strickler JH, Niedzwiecki D, Zemla T, et al. A Phase II, open label study of tucatinib (ONT-380) combined with trastuzumab in patients with HER2+ metastatic colorectal cancer (mCRC)(MOUNTAINEER). J Clin Oncol. 2016;Abstract TPS3624.
   Google Scholar
• Sartore-Bianchi A, Trusolino L, Martino C, et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, Phase 2 trial. Lancet Oncol. 2016;17(6):738–746. doi:10.1016/S1470-2045(16)00150-9
   PubMed Web of Science ®Google Scholar
• Meric-Bernstam F, Hurwitz H, Raghav KPS, et al. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2019;20(4):518–530. doi:10.1016/S1470-2045(18)30904-5
   PubMed Web of Science ®Google Scholar
• Sartore-Bianchi A, Martino C, Lonardi S, et al. Phase II study of pertuzumab and trastuzumab-emtansine (T-DM1) in patients with HER2-positive metastatic colorectal cancer: the HERACLES-B (HER2 amplification for colo-rectal cancer enhanced stratification, cohort B) trial. Annals Oncology. 2019;30(5):V869870. doi:10.1093/annonc/mdz394.024
   Google Scholar
• Tukysa^TM (Tucatinib) Tablets for Oral Use [Package Insert]. Seattle Genetics, Inc; 2020.
   Google Scholar
• Tykerb (Lapatinib) Tablets [Package Insert]. Novartis; 2018.
   Google Scholar
• Moulder SL, Borges VF, Baetz T, et al. Phase I study of ONT-380, a HER2 inhibitor, in patients with HER2+-advanced solid tumors, with an expansion cohort in HER2+ metastatic breast cancer (MBC). Clinical Cancer Research. 2017;23(14):3529–3536. doi:10.1158/1078-0432.CCR-16-1496
   PubMed Web of Science ®Google Scholar
• Kulukian A, Lee P, Taylor J, et al. Preclinical activity of HER2-selective tyrosine kinase inhibitor tucatinib as a single agent or in combination with trastuzumab or docetaxel in solid tumor models. Mol Cancer Ther. 2020;19(4):976–987. doi:10.1158/1535-7163.MCT-19-0873
   PubMed Web of Science ®Google Scholar
• Strickler JH, Zemla T, Ou F-S, et al. Trastuzumab and tucatinib for the treatment of HER2 amplified metastatic colorectal cancer (mCRC): initial results from the MOUNTAINEER trial. Annals Oncology. 2019;30(5):V200. doi:10.1093/annonc/mdz246.005
   Google Scholar
• Siena S, Di Bartolomeo M, Raghav KPS, et al. A phase II, multicenter, open-label study of trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): DESTINY-CRC01. J Clin Oncol. 2020;38(15):Abstract 4000. doi:10.1200/JCO.2020.38.15_suppl.4000
   Web of Science ®Google Scholar
• Mitani S, Kawakami H. Emerging targeted therapies for HER2 positive gastric cancer that can overcome trastuzumab resistance. Cancers. 2020;12(2):400. doi:10.3390/cancers12020400
   PubMed Web of Science ®Google Scholar
• Yap T, O’Carrigan B, Penney MS, et al. Phase I trial of first-in-class ATR inhibitor M6620 (VX-970) as monotherapy or in combination with carboplatin in patients with advanced solid tumors. J Clin Oncol. 2020;38(27):3195–3204. doi:10.1200/JCO.19.02404
   PubMed Web of Science ®Google Scholar
• Reaper PM, Griffiths MR, Long JM, et al. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat Chem Biol. 2011;7:428–430. doi:10.1038/nchembio.573
   PubMed Web of Science ®Google Scholar
• The Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(330337). doi:10.1038/nature11252
   Web of Science ®Google Scholar
• Valsasina B, Beria I, Alli C, et al. NMS-P937, an orally available, specific small-molecule polo-like kinase 1 inhibitor with antitumor activity in solid and hematologic malignancies. Mol Cancer Ther. 2012;11(4):1006–1016. doi:10.1158/1535-7163.MCT-11-0765
   PubMed Web of Science ®Google Scholar
• Weiss GJ, Jameson G, Von Hoff DD, et al. Phase I dose escalation study of NMS-1286937, an orally available polo-like kinase 1 inhibitor, in patients with advanced or metastatic solid tumors. Invest New Drugs. 2018;36:85–95. doi:10.1007/s10637-017-0491-7
   Web of Science ®Google Scholar
• Kumar S, Kim J. PLK-1 targeted inhibitors and their potential against tumorigenesis. Phytochemicals Cancer Prevention Therapy. 2015;2015:705745.
   Google Scholar
• Soria JC, Massard C, Magné N, et al. Phase 1 dose-escalation study of oral tyrosine kinase inhibitor masitinib in advanced and/or metastatic solid cancers. Eur J Cancer. 2009;45(12):2333–2341.
   Web of Science ®Google Scholar
• Dubreuil P, Letard S, Ciufolini M, et al. Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS One. 2009;4(9):e7258.
   PubMed Web of Science ®Google Scholar
• Gavert N, Shvab A, Sheffer M, et al. c-Kit is suppressed in human colon cancer tissue and contributes to L1-mediated metastases. Cancer Res. 2013;73(18):5754–5763. doi:10.1158/0008-5472.CAN-13-0576
   PubMed Web of Science ®Google Scholar
• Taieb J, Borg C, Lecomte T, et al. Masitinib plus FOLFIRI for second line treatment of metastatic colorectal cancer: an open label phase Ib/II trial. J Clin Oncol. 2015;33(15):3526. doi:10.1200/jco.2015.33.15_suppl.3526
   Web of Science ®Google Scholar
• Do K, Wilsker D, Ji J, et al. Phase I study of single-agent AZD1775 (MK-1775), a Wee1 kinase inhibitor, in patients with refractory solid tumors. J Clin Oncol. 2015;33(30):3409–3415. doi:10.1200/JCO.2014.60.4009
   PubMed Web of Science ®Google Scholar
• Webster PJ, Littlejohns AT, Gaunt HJ, et al. AZD1775 induces toxicity through double-stranded DNA breaks independently of chemotherapeutic agents in p53-mutated colorectal cancer cells. Cell Cycle. 2017;16(22):2176–2182. doi:10.1080/15384101.2017.1301329
   PubMed Web of Science ®Google Scholar
• Mayer RJ, Van Cutsem E, Falcone A, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015;372:1909–1919. doi:10.1056/NEJMoa1414325
   PubMed Web of Science ®Google Scholar
• Pfeiffer P, Yilmaz M, Möller S, et al. TAS-102 with or without bevacizumab in patients with chemorefractory metastatic colorectal cancer: an investigator-initiated, open-label, randomised, phase 2 trial. Lancet Oncol. 2020;21:412–420. doi:10.1016/S1470-2045(19)30827-7
   Web of Science ®Google Scholar
• Andre T, Shiu K, Kim TW, et al. Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: the phase 3 KEYNOTE-177 study. J Clin Oncol. 2020;38(18):Abstract LBA4. doi:10.1200/JCO.2020.38.18_suppl.LBA4
   Web of Science ®Google Scholar
• Lenz H, Lonardi S, Zagonel V, et al. Nivolumab plus low-dose ipilimumab as first-line therapy in microsatellite instability-high/DNA mismatch repair deficient metastatic colorectal cancer: clinical update. J Clin Oncol. 2020;38(suppl4; abstr 11).
   Google Scholar
• Battaglin F, Naseem M, Lenz H, et al. Microsatellite instability in colorectal cancer: overview of its clinical significance and novel perspectives. Clinical Advances Hematol Oncol. 2018;16(11):735–747.
   PubMed Web of Science ®Google Scholar
• Antoniotti C, Borelli B, Rossini D, et al. AtezoTRIBE: a randomised phase II study of FOLFOXIRI plus bevacizumab alone or in combination with atezolizumab as initial therapy for patients with unresectable metastatic colorectal cancer. BMC Cancer. 2020;20(683):4. doi:10.1186/s12885-020-07169-6
   Web of Science ®Google Scholar
• Fukuoka S, Hara H, Takahashi N, et al. Regorafenib plus nivolumab in patients with advanced gastric or colorectal cancer: an open-label, dose-escalation, and dose-expansion phase Ib trial (REGONIVO, EPOC1603). J Clin Oncol. 2020;38(18):2053–2061. doi:10.1200/JCO.19.03296
   PubMed Web of Science ®Google Scholar
• Cousin S, Bellera CA, Guégan JP, et al. REGOMUNE: A phase II study of regorafenib plus avelumab in solid tumors—Results of the non-MSI-H metastatic colorectal cancer (mCRC) cohort. J Clin Oncol. 2020;38(15):Abstract 4019. doi:10.1200/JCO.2020.38.15_suppl.4019
   Google Scholar
• Gou M, Yan H, E L T, et al. Fruquintinib combination with sintilimab in refractory metastatic colorectal cancer patients in China. J Clin Oncol. 2020;38(15):Abstract 4028. doi:10.1200/JCO.2020.38.15_suppl.4028
   Web of Science ®Google Scholar
• Hughes PE, Caenepeel S, Wu LC. Targeted therapy and checkpoint immunotherapy combinations for the treatment of cancer. Trends Immunol. 2016;37(7):462–476. doi:10.1016/j.it.2016.04.010
   PubMed Web of Science ®Google Scholar
• Gu tzmer R, Stroyakovskiy D, Gogas H, et al. Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAF V600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020;395(10240):1835–1844. doi:10.1016/S0140-6736(20)30934-X
   Web of Science ®Google Scholar
• Stein A, Binder M, Goekkurt E, et al. Avelumab and cetuximab in combination with FOLFOX in patients with previously untreated metastatic colorectal cancer (MCRC): final results of the phase II AVETUX trial (AIO-KRK-0216). J Clin Oncol. 2020;38(suppl4; abstr 96):96. doi:10.1200/JCO.2020.38.4_suppl.96
   Google Scholar