Current Treatment Landscape for Third- or Later-Line Therapy in Metastatic Colorectal Cancer

1.

Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145–64.

PubMed  Google Scholar 

2.

Field K, Lipton L. Metastatic colorectal cancer-past, progress and future. World J Gastroenterol. 2007;13(28):3806–15.

CAS  PubMed  PubMed Central  Google Scholar 

3.

Jonker DJ, O’Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007;357(20):2040–8.

CAS  PubMed  Google Scholar 

4.

NCC N. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Colon Cancer Version 2.2021. 2021.

5.

Xie YH, Chen YX, Fang JY. Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther. 2020;5(1):22.

CAS  PubMed  PubMed Central  Google Scholar 

6.

Kish T, Uppal P. Trifluridine/tipiracil (lonsurf) for the treatment of metastatic colorectal cancer. P T. 2016;41(5):314–25.

PubMed  PubMed Central  Google Scholar 

7.

Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia-Carbonero R, Mizunuma N, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015;372(20):1909–19.

PubMed  Google Scholar 

8.

Yoshino T, Mizunuma N, Yamazaki K, Nishina T, Komatsu Y, Baba H, et al. TAS-102 monotherapy for pretreated metastatic colorectal cancer: a double-blind, randomised, placebo-controlled phase 2 trial. Lancet Oncol. 2012;13(10):993–1001.

CAS  PubMed  Google Scholar 

9.

Xu J, Kim TW, Shen L, Sriuranpong V, Pan H, Xu R, et al. Results of a randomized, double-blind, placebo-controlled, phase iii trial of trifluridine/tipiracil (TAS-102) monotherapy in Asian patients with previously treated metastatic colorectal cancer: the TERRA study. J Clin Oncol. 2018;36(4):350–8.

CAS  PubMed  Google Scholar 

10.

Ettrich T.J. ST. Regorafenib. Small Molecules in Oncology Recent Results in Cancer Research. 211. August 2, 2018 ed: Springer, Cham; 2018.

11.

Grothey A, Prager G, Yoshino T. The mechanism of action of regorafenib in colorectal cancer: a guide for the community physician. Clin Adv Hematol Oncol. 2019;17(Suppl 12(8)):1–19.

PubMed  Google Scholar 

12.

Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303–12.

CAS  PubMed  Google Scholar 

13.

Li J, Qin S, Xu R, Yau TC, Ma B, Pan H, et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015;16(6):619–29.

CAS  PubMed  Google Scholar 

14.

Adenis A, de la Fouchardiere C, Paule B, Burtin P, Tougeron D, Wallet J, et al. Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program. BMC Cancer. 2016;16:412.

PubMed  PubMed Central  Google Scholar 

15.

Reiss KA, Yu S, Mamtani R, Mehta R, D’Addeo K, Wileyto EP, et al. Starting dose of sorafenib for the treatment of hepatocellular carcinoma: a retrospective, multi-institutional study. J Clin Oncol. 2017;35(31):3575–81.

CAS  PubMed  PubMed Central  Google Scholar 

16.•

Bekaii-Saab TS, Ou FS, Ahn DH, Boland PM, Ciombor KK, Heying EN, et al. 2018 Regorafenib dose-optimisation in patients with refractory metastatic colorectal cancer (ReDOS): a randomised, multicentre, open-label, phase 2 study. Lancet Oncol. 2019;20(8):1070–82. Novel study demonstrating effiacy of modified dosing schema with regorafenib.

17.

Moriwaki T, Fukuoka S, Taniguchi H, Takashima A, Kumekawa Y, Kajiwara T, et al. Propensity score analysis of regorafenib versus trifluridine/tipiracil in patients with metastatic colorectal cancer refractory to standard chemotherapy (REGOTAS): a Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study. Oncologist. 2018;23(1):7–15.

CAS  PubMed  Google Scholar 

18.

Masuishi T, Taniguchi H, Hamauchi S, Komori A, Kito Y, Narita Y, et al. Regorafenib versus trifluridine/tipiracil for refractory metastatic colorectal cancer: a retrospective comparison. Clin Colorectal Cancer. 2017;16(2):e15–22.

PubMed  Google Scholar 

19.

Van Cutsem E, Mayer RJ, Laurent S, Winkler R, Gravalos C, Benavides M, et al. The subgroups of the phase III RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo with best supportive care in patients with metastatic colorectal cancer. Eur J Cancer. 2018;90:63–72.

PubMed  Google Scholar 

20.

Vogel A, Hofheinz RD, Kubicka S, Arnold D. Treatment decisions in metastatic colorectal cancer - beyond first and second line combination therapies. Cancer Treat Rev. 2017;59:54–60.

CAS  PubMed  Google Scholar 

21.

Satake H, Kato T, Oba K, Kotaka M, Kagawa Y, Yasui H, et al. Phase Ib/II study of biweekly TAS-102 in combination with bevacizumab for patients with metastatic colorectal cancer refractory to standard therapies (BiTS study). Oncologist. 2020;25(12):e1855–63.

CAS  PubMed  Google Scholar 

22.

Cecchini M, Kortmansky JS, Cui C, Wei W, Thumar JR, Uboha NV, et al. A phase 1b expansion study of TAS-102 with oxaliplatin for refractory metastatic colorectal cancer. Cancer. 2020.

23.

Varghese AM, Cardin DB, Hersch J, Benson AB, Hochster HS, Makris L, et al. Phase I study of trifluridine/tipiracil plus irinotecan and bevacizumab in advanced gastrointestinal tumors. Clin Cancer Res. 2020;26(7):1555–62.

CAS  PubMed  Google Scholar 

24.

Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26(12):2013–9.

CAS  PubMed  Google Scholar 

25.

Matsuda C, Honda M, Tanaka C, Fukunaga M, Ishibashi K, Munemoto Y, et al. Multicenter randomized phase II clinical trial of oxaliplatin reintroduction as a third- or later-line therapy for metastatic colorectal cancer-biweekly versus standard triweekly XELOX (The ORION Study). Int J Clin Oncol. 2016;21(3):566–72.

CAS  PubMed  Google Scholar 

26.

Costa T, Nunez J, Felismino T, Boente L, Mello C. REOX: evaluation of the efficacy of retreatment with an oxaliplatin-containing regimen in metastatic colorectal cancer: a retrospective single-center study. Clin Colorectal Cancer. 2017;16(4):316–23.

PubMed  Google Scholar 

27.

Yin J, Cohen R, Jin Z, Liu H, Pederson L, Adams R, et al. Prognostic and predictive impact of primary tumor sidedness for previously untreated advanced colorectal cancer. J Natl Cancer Inst. 2021.

28.

Karani A, Felismino TC, Diniz L, Macedo MP, Silva VSE, Mello CA. Is there a role for rechallenge and reintroduction of anti-EGFR plus chemotherapy in later lines of therapy for metastatic colorectal carcinoma? A retrospective analysis Ecancermedicalscience. 2020;14:1069.

PubMed  Google Scholar 

29.

Wadlow RC, Hezel AF, Abrams TA, Blaszkowsky LS, Fuchs CS, Kulke MH, et al. Panitumumab in patients with KRAS wild-type colorectal cancer after progression on cetuximab. Oncologist. 2012;17(1):14.

PubMed  PubMed Central  Google Scholar 

30.

Siravegna G, Mussolin B, Buscarino M, Corti G, Cassingena A, Crisafulli G, et al. Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients. Nat Med. 2015;21(7):827.

CAS  PubMed  Google Scholar 

31.••

Parseghian CM, Loree JM, Morris VK, Liu X, Clifton KK, Napolitano S, et al. Anti-EGFR-resistant clones decay exponentially after progression: implications for anti-EGFR re-challenge. Ann Oncol. 2019;30(2):243–9. Important analysis providing insight on decay of resistant clones following EGFR targeted therapy.

32

Rossini D, Germani MM, Pagani F, Pellino A, Dell’Aquila E, Bensi M, et al. Retreatment with anti-EGFR antibodies in metastatic colorectal cancer patients: a multi-institutional analysis. Clin Colorectal Cancer. 2020;19(3):191-9 e6.

PubMed  Google Scholar 

33.••

Cremolini C, Rossini D, Dell’Aquila E, Lonardi S, Conca E, Del Re M, et al. Rechallenge for patients with RAS and BRAF wild-type metastatic colorectal cancer with acquired resistance to first-line cetuximab and irinotecan: a phase 2 single-arm clinical trial. JAMA Oncol. 2019;5(3):343–50. Key study demonstrating efficacy of re-challenge and potential value of ctDNA.

34.••

Martinelli E, Martini G, Famiglietti V, Troiani T, Napolitano S, Pietrantonio F, et al. Cetuximab rechallenge plus avelumab in pretreated patients with RAS wild-type metastatic colorectal cancer: the phase 2 single-arm clinical CAVE trial. JAMA Oncol. 2021. Recent study reinforcing value of ctDNA in predicting efficacy of EGFR re-challenge.

35.

Sartore-Bianchi A PF, Lonardi S, Mussolin B, Rua F, Fenocchio E, et al. Phase II study of anti-EGFR rechallenge therapy with panitumumab driven by circulating tumor DNA molecular selection in metastatic colorectal cancer: the CHRONOS trial. Journal of Clinical Oncology. 2021;39, no. 15_suppl 3506.

36.

Hochster HS, Hart LL, Ramanathan RK, Childs BH, Hainsworth JD, Cohn AL, et al. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol. 2008;26(21):3523–9.

CAS  PubMed  Google Scholar 

37.

Bennouna J, Sastre J, Arnold D, Osterlund P, Greil R, Van Cutsem E, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013;14(1):29–37.

CAS  PubMed  Google Scholar 

38.

Bennouna J, Hiret S, Bertaut A, Bouche O, Deplanque G, Borel C, et al. Continuation of bevacizumab vs cetuximab plus chemotherapy after first progression in KRAS wild-type metastatic colorectal cancer: the UNICANCER PRODIGE18 randomized clinical trial. JAMA Oncol. 2019;5(1):83–90.

PubMed  Google Scholar 

39.

Masi G, Salvatore L, Boni L, Loupakis F, Cremolini C, Fornaro L, et al. Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: final results of the randomized BEBYP trial. Ann Oncol. 2015;26(4):724–30.

CAS  PubMed  Google Scholar 

40.

Sun Q, Zhou J, Zhang Z, Guo M, Liang J, Zhou F, et al. Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014;15(12):1635–45.

CAS  PubMed  PubMed Central  Google Scholar 

41.

Cao J, Zhang J, Peng W, Chen Z, Fan S, Su 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(2):259–69.

CAS  PubMed  Google Scholar 

42.••

Li J, Qin S, Xu RH, Shen L, Xu J, Bai Y, 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):2486–96. Pivotal phase III study demonstrating efficacy of fruquintinib in Asian population.

43.

Kuboki Y, Nishina T, Shinozaki E, Yamazaki K, Shitara K, Okamoto W, et al. TAS-102 plus bevacizumab for patients with metastatic colorectal cancer refractory to standard therapies (C-TASK FORCE): an investigator-initiated, open-label, single-arm, multicentre, phase 1/2 study. Lancet Oncol. 2017;18(9):1172–81.

CAS  PubMed  Google Scholar 

44.

Yamazaki K KY, Shinozaki E, Hara H, Komatsu Y, Nishina T, et al. A multicentre phase I/II study of TAS-102 with nintedanib in patients with metastatic colorectal cancer refractory to standard therapies (N-task force: EPOC1410). Ann Oncol. 2017;28, suppl_5.

45.

Boland PM FM, Lim D, Attwood K, Tan W, Mastri M, et al. A phase I/II study of nintedanib and capecitabine in refractory metastatic colorectal cancer. J Clin Oncol. 2018;36, no. 15_suppl.

46.••

Pfeiffer P, Yilmaz M, Moller S, Zitnjak D, Krogh M, Petersen LN, 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(3):412–20. Randomized study demonstrating efficacy of adding anti-angiogenic therapy to fluoropyrimidine in 3rd-line setting.

47.

Arteaga CL, Engelman JA. ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell. 2014;25(3):282–303.

CAS  PubMed  PubMed Central  Google Scholar 

48.

Ross JS, Fakih M, Ali SM, Elvin JA, Schrock AB, Suh J, et al. Targeting HER2 in colorectal cancer: the landscape of amplification and short variant mutations in ERBB2 and ERBB3. Cancer. 2018;124(7):1358–73.

CAS  PubMed  Google Scholar 

49.

Nowak JA. HER2 in colorectal carcinoma: are we there yet? Surg Pathol Clin. 2020;13(3):485–502.

PubMed  Google Scholar 

50.

Salem ME, Weinberg BA, Xiu J, El-Deiry WS, Hwang JJ, Gatalica Z, et al. Comparative molecular analyses of left-sided colon, right-sided colon, and rectal cancers. Oncotarget. 2017;8(49):86356–68.

PubMed  PubMed Central 

Comments (0)

No login
gif