112
Views
0
CrossRef citations to date
0
Altmetric
Review

Progress in the treatment of anal cancer: an overview of the latest investigational drugs

&
Pages 145-157 | Received 14 Nov 2023, Accepted 24 Jan 2024, Published online: 30 Jan 2024

References

  • Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. doi: 10.3322/caac.21492
  • Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48. doi: 10.3322/caac.21763
  • Cancer of the anus, anal canal, and anorectum – cancer stat facts. SEER. [cited Oct 4, 2023]. Available from: https://seer.cancer.gov/statfacts/html/anus.html
  • Benson AB, Venook AP, Al-Hawary MM, et al. Anal Carcinoma, Version 2.2023, NCCN clinical practice guidelines in oncology. J National Compr Cancer Network. 2023;21(6):653–677.
  • Anal cancer statistics. Cancer Research UK. [cited Oct 4, 2023]. Available from :https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/anal-cancer
  • Nelson VM, Benson AB. Epidemiology of anal canal cancer. Surg Oncol Clin N Am. 2017;26(1):9–15. doi: 10.1016/j.soc.2016.07.001
  • Ortiz-Ortiz KJ, Ramos-Cartagena JM, Deshmukh AA, et al. Squamous cell carcinoma of the anus incidence, mortality, and survival among the general population and persons living with HIV in Puerto rico, 2000–2016. JCO Glob Oncol. 2021;7(7):133–143.
  • Stewart DB, Gaertner WB, Glasgow SC, et al. The American society of colon and rectal surgeons clinical practice guidelines for anal squamous cell cancers (revised 2018). Dis Colon Rectum. 2018;61(7):755–774. doi: 10.1097/DCR.0000000000001114
  • Rao S, Guren MG, Khan K, et al. Anal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up☆. Ann Oncol. 2021;32(9):1087–1100. doi: 10.1016/j.annonc.2021.06.015
  • Cummings BJ. Metastatic anal cancer: the search for cure. Onkologie. 2006;29(1–2):5–6. doi: 10.1159/000090747
  • Nigro ND, Vaitkevicius VK, Considine B. Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum. 1974;17(3):354–356. doi: 10.1007/BF02586980
  • UKCCCR Anal Cancer Trial Working Party. Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. Lancet. 1996;348(9034):1049–1054. doi: 10.1016/S0140-6736(96)03409-5
  • Bartelink H, Roelofsen F, Eschwege F, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European organization for Research and treatment of cancer radiotherapy and gastrointestinal cooperative groups. J Clin Oncol. 1997;15(5):2040–2049.
  • Northover J, Glynne-Jones R, Sebag-Montefiore D, et al. Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR anal cancer trial (ACT I). Br J Cancer. 2010;102(7):1123–1128. doi: 10.1038/sj.bjc.6605605
  • Flam M, John M, Pajak TF, et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol. 1996;14(9):2527–2539. doi: 10.1200/JCO.1996.14.9.2527
  • Ajani JA, Winter KA, Gunderson LL, et al. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA. 2008;299(16):1914–1921.
  • Gunderson LL, Winter KA, Ajani JA, et al. Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin. J Clin Oncol. 2012;30(35):4344–4351. doi: 10.1200/JCO.2012.43.8085
  • Peiffert D, Tournier-Rangeard L, Gérard JP, et al. Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized UNICANCER ACCORD 03 trial. J Clin Oncol. 2012;30(16):1941–1948. doi: 10.1200/JCO.2011.35.4837
  • James RD, Glynne-Jones R, Meadows HM, et al. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial. Lancet Oncol. 2013;14(6):516–524. doi: 10.1016/S1470-2045(13)70086-X
  • Glynne-Jones R, Meadows H, Wan S, et al. EXTRA—A multicenter phase II study of chemoradiation using a 5 day per week oral regimen of capecitabine and intravenous mitomycin C in anal cancer. Int J Radiat Oncol Biol Phys. 2008;72(1):119–126. doi: 10.1016/j.ijrobp.2007.12.012
  • Oliveira SCR, Moniz CMV, Riechelmann R, et al. Phase II study of capecitabine in substitution of 5-FU in the chemoradiotherapy regimen for patients with localized squamous cell carcinoma of the anal canal. J Gastrointest Cancer. 2016;47(1):75–81. doi: 10.1007/s12029-015-9790-4
  • Meulendijks D, Dewit L, Tomasoa NB, et al. Chemoradiotherapy with capecitabine for locally advanced anal carcinoma: an alternative treatment option. Br J Cancer. 2014;111(9):1726–1733. doi: 10.1038/bjc.2014.467
  • Goodman KA, Rothenstein D, Lajhem C, et al. Capecitabine plus mitomycin in patients undergoing definitive chemoradiation for anal squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2014;90(1):S32–S33. doi: 10.1016/j.ijrobp.2014.05.141
  • Rao S, Sclafani F, Eng C, et al. International rare cancers initiative multicenter randomized phase II trial of cisplatin and fluorouracil versus carboplatin and paclitaxel in advanced anal cancer: interAAct. J Clin Oncol. 2020;38(22):2510–2518. doi: 10.1200/JCO.19.03266
  • Kim S, Jary M, Mansi L, et al. DCF (docetaxel, cisplatin and 5-fluorouracil) chemotherapy is a promising treatment for recurrent advanced squamous cell anal carcinoma. Ann Oncol. 2013;24(12):3045–3050. doi: 10.1093/annonc/mdt396
  • Kim S, François E, André T, et al. Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (epitopes-HPV02): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2018;19(8):1094–1106. doi: 10.1016/S1470-2045(18)30321-8
  • Kim S, Meurisse A, Spehner L, et al. Pooled analysis of 115 patients from updated data of epitopes-HPV01 and epitopes-HPV02 studies in first-line advanced anal squamous cell carcinoma. Ther Adv Med Oncol. 2020;12:1758835920975356. doi: 10.1177/1758835920975356
  • Kim S, Vendrely V, Saint A, et al. DCF versus doublet chemotherapy as first-line treatment of advanced squamous anal cell carcinoma: a multicenter propensity score-matching study. Exp Hematol Oncol. 2023;12(1):63. doi: 10.1186/s40164-023-00413-2
  • Mondaca S, Chatila WK, Bates D, et al. FOLFCIS treatment and genomic correlates of response in advanced anal squamous cell cancer. Clin Colorectal Cancer. 2019;18(1):e39–e52. doi: 10.1016/j.clcc.2018.09.005
  • Matsunaga M, Miwa K, Oka Y, et al. Successful Treatment of Metastatic Anal Canal Adenocarcinoma with mFOLFOX6 + bevacizumab. Case Rep Oncol. 2016;9(1):249–254. doi: 10.1159/000446107
  • Ott PA, Piha-Paul SA, Munster P, et al. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol. 2017;28(5):1036–1041. doi: 10.1093/annonc/mdx029
  • Marabelle A, Cassier PA, Fakih M, et al. Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study. Lancet Gastroenterol Hepatol. 2022;7(5):446–454. doi: 10.1016/S2468-1253(21)00382-4
  • Morris VK, Salem ME, Nimeiri H, et al. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017;18(4):446–453. doi: 10.1016/S1470-2045(17)30104-3
  • Rao S, Anandappa G, Capdevila J, et al. A phase II study of retifanlimab (INCMGA00012) in patients with squamous carcinoma of the anal canal who have progressed following platinum-based chemotherapy (POD1UM-202). ESMO Open. 2022;7(4):100529. doi: 10.1016/j.esmoop.2022.100529
  • Morris V, Ciombor K, Polite B, et al. O-12 NCI9673 (part B): a multi-institutional ETCTN randomized phase II study of nivolumab with or without ipilimumab in refractory, metastatic squamous cell carcinoma of the anal canal. Ann Oncol. 2023;34:S185–S186. doi: 10.1016/j.annonc.2023.04.027
  • Morris V, Liu S, Johnson B, et al. 403MO atezolizumab in combination with bevacizumab for patients with unresectable/metastatic anal cancer. Ann Oncol. 2020;31:S412. doi: 10.1016/j.annonc.2020.08.514
  • Lonardi S, Prete AA, Morano F, et al. Randomized phase II trial of avelumab alone or in combination with cetuximab for patients with previously treated, locally advanced, or metastatic squamous cell anal carcinoma: the CARACAS study. J Immunother Cancer. 2021;9(11):e002996. doi: 10.1136/jitc-2021-002996
  • Kim S, Ghiringhelli F, De La Fouchardiere C, et al. Atezolizumab plus modified DCF (docetaxel, cisplatin, and 5-fluorouracil) as first-line treatment for metastatic or locally advanced squamous cell anal carcinoma: a SCARCE-PRODIGE 60 randomized phase II study. JCO. 2022;40(16_suppl):3508–3508. doi: 10.1200/JCO.2022.40.16_suppl.3508
  • De Vuyst H, Clifford GM, Nascimento MC, et al. Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer. 2009;124(7):1626–1636. doi: 10.1002/ijc.24116
  • Pal A, Kundu R. Human papillomavirus E6 and E7: the cervical cancer hallmarks and targets for therapy. Front Microbiol. 2020;10:3116. doi: 10.3389/fmicb.2019.03116
  • Allouch S, Malki A, Allouch A, et al. High-risk HPV oncoproteins and PD-1/PD-L1 interplay in human cervical cancer: recent evidence and future directions. Front Oncol. 2020;10:914. doi: 10.3389/fonc.2020.00914
  • Wang J, Sun H, Zeng Q, et al. HPV-positive status associated with inflamed immune microenvironment and improved response to anti-PD-1 therapy in head and neck squamous cell carcinoma. Sci Rep. 2019;9(1):13404. doi: 10.1038/s41598-019-49771-0
  • Guidelines Detail. NCCN. [cited Oct 10, 2023]. Available from: https://www.nccn.org/guidelines/guidelines-detail
  • Grignani G, Rutkowski P, Lebbe C, et al. 545 a phase 2 study of retifanlimab in patients with advanced or metastatic merkel cell carcinoma (MCC) (POD1UM-201). J Immunother Cancer. 2021;9(Suppl 2):A574–A575. doi: 10.1136/jitc-2021-SITC2021.545
  • Mencel J, Rao S. Retifanlimab and other immune checkpoint inhibitors for squamous cell anal carcinoma. TouchREVIEWS Oncol Haematol. 2023;19(1). https://touchoncology.com/immunotherapy/journal-articles/retifanlimab-and-other-immune-checkpoint-inhibitors-for-squamous-cell-anal-carcinoma/
  • Lê LH, Chetty R, Moore MJ. Epidermal growth factor receptor expression in anal canal carcinoma. Am J Clin Pathol. 2005;124(1):20–23. doi: 10.1309/X4UADHVN317V2XMW
  • Tsai TC, Chen SL. The biochemical and biological functions of human papillomavirus type 16 E5 protein. Arch Virol. 2003;148(8):1445–1453. doi: 10.1007/s00705-003-0111-z
  • Morris V, Rao X, Pickering C, et al. Comprehensive genomic profiling of metastatic squamous cell carcinoma of the anal canal. Mol Cancer Res. 2017;15(11):1542–1550. doi: 10.1158/1541-7786.MCR-17-0060
  • Bourhis J, Stein A, Paul de Boer J, et al. Avelumab and cetuximab as a therapeutic combination: an overview of scientific rationale and current clinical trials in cancer. Cancer Treat Rev. 2021;97:102172. doi: 10.1016/j.ctrv.2021.102172
  • Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894–1905. doi: 10.1056/NEJMoa1915745
  • Wallin JJ, Bendell JC, Funke R, et al. Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma. Nat Commun. 2016;7(1):12624. doi: 10.1038/ncomms12624
  • Hegde PS, Wallin JJ, Mancao C. Predictive markers of anti-VEGF and emerging role of angiogenesis inhibitors as immunotherapeutics. Semin Cancer Biol. 2018;52:117–124. doi: 10.1016/j.semcancer.2017.12.002
  • Sparano JA, Lee JY, Palefsky J, et al. Cetuximab plus chemoradiotherapy for HIV-Associated anal carcinoma: a phase II AIDS malignancy consortium trial. J Clin Oncol. 2017;35(7):727–733. doi: 10.1200/JCO.2016.69.1642
  • Garg MK, Zhao F, Sparano JA, et al. Cetuximab plus chemoradiotherapy in immunocompetent patients with anal carcinoma: a phase II Eastern cooperative oncology group–american college of radiology imaging network cancer research group trial (E3205). J Clin Oncol. 2017;35(7):718–726. doi: 10.1200/JCO.2016.69.1667
  • Feliu J, Garcia‐Carbonero R, Capdevila J, et al. VITAL phase 2 study: upfront 5‐fluorouracil, mitomycin‐C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09‐02). Cancer Med. 2019;9(3):1008–1016.
  • Rogers JE, Ohinata A, Silva NN, et al. Epidermal growth factor receptor inhibition in metastatic anal cancer. Anticancer Drugs. 2016;27(8):804–808. doi: 10.1097/CAD.0000000000000383
  • Kim DW, Byer J, Kothari N, et al. EGFR inhibitors in patients with advanced squamous cell anal carcinomas: a single-institution experience. Oncology. 2017;92(4):190–196. doi: 10.1159/000452766
  • Watanabe J, Muro K, Shitara K, et al. Panitumumab vs Bevacizumab added to standard first-line chemotherapy and overall survival among patients with RAS wild-type, left-sided metastatic colorectal cancer: a randomized clinical trial. JAMA. 2023;329(15):1271–1282. doi: 10.1001/jama.2023.4428
  • Rogers JE, Leung M, Johnson B. Metastatic or locally recurrent anal squamous cell carcinoma (SCAC): Current clinical trial landscape and novel approaches. Cancer Manage Res. 2022;14:2065–2077. doi: 10.2147/CMAR.S331429
  • Bedard PL, Hernando-Calvo A, Carvajal RD, et al. A phase 1 trial of the bifunctional EGFR/TGFβ fusion protein BCA101 alone and in combination with pembrolizumab in patients with advanced solid tumors. JCO. 2022;40(16_suppl):2513–2513. doi: 10.1200/JCO.2022.40.16_suppl.2513
  • Hanna GJ, Kaczmar JM, Zandberg DP, et al. Dose expansion results of the bifunctional EGFR/TGFβ inhibitor BCA101 with pembrolizumab in patients with recurrent, metastatic head and neck squamous cell carcinoma. JCO. 2023;41(16_suppl):6005–6005. doi: 10.1200/JCO.2023.41.16_suppl.6005
  • Trimble CL, Morrow MP, Kraynyak KA, et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Lancet. 2015;386(10008):2078–2088. doi: 10.1016/S0140-6736(15)00239-1
  • Harper DM, Nieminen P, Donders G, et al. The efficacy and safety of tipapkinogen sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3: randomized controlled phase II trial with 2.5 years of follow-up. Gynecol Oncol. 2019;153(3):521–529. doi: 10.1016/j.ygyno.2019.03.250
  • Yan F, Cowell LG, Tomkies A, et al. Therapeutic vaccination for HPV-Mediated cancers. Curr Otorhinolaryngol Rep. 2023;11(1):44–61. doi: 10.1007/s40136-023-00443-8
  • Eng C, Fakih M, Amin M, et al. A phase II study of axalimogene filolisbac for patients with previously treated, unresectable, persistent/recurrent loco-regional or metastatic anal cancer. Oncotarget. 2020;11(15):1334–1343. doi: 10.18632/oncotarget.27536
  • Morris VK, Jazaeri A, Westin SN, et al. Phase II trial of MEDI0457 and durvalumab for patients with recurrent/metastatic human papillomavirus-associated cancers. Oncology. 2023;28(7):618–623. doi: 10.1093/oncolo/oyad085
  • Youn JW, Hur SY, Woo JW, et al. Pembrolizumab plus GX-188E therapeutic DNA vaccine in patients with HPV-16-positive or HPV-18-positive advanced cervical cancer: interim results of a single-arm, phase 2 trial. Lancet Oncol. 2020;21(12):1653–1660. doi: 10.1016/S1470-2045(20)30486-1
  • Chung HC, Ros W, Delord JP, et al. Efficacy and safety of Pembrolizumab in Previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2019;37(17):1470–1478. doi: 10.1200/JCO.18.01265
  • Massarelli E, William W, Johnson F, et al. Combining immune checkpoint blockade and tumor-specific vaccine for patients with incurable human papillomavirus 16-related cancer: a phase 2 clinical trial. JAMA Oncol. 2019;5(1):67–73.
  • Ferris RL, Blumenschein G, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856–1867. doi: 10.1056/NEJMoa1602252
  • Mehra R, Seiwert TY, Gupta S, et al. Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012. Br J Cancer. 2018;119(2):153–159. doi: 10.1038/s41416-018-0131-9
  • Heinhuis KM, Ros W, Kok M, et al. Enhancing antitumor response by combining immune checkpoint inhibitors with chemotherapy in solid tumors. Ann Oncol. 2019;30(2):219–235. doi: 10.1093/annonc/mdy551
  • Roth MT, Catalano PJ, Ciombor KK, et al. A randomized phase III study of immune checkpoint inhibition with chemotherapy in treatment-naive metastatic anal cancer patients: a trial of the ECOG-ACRIN cancer research group (EA2176). JCO. 2021;39(15_suppl):TPS3614–TPS3614. doi: 10.1200/JCO.2021.39.15_suppl.TPS3614
  • Rao S, Jones M, Bowman J, et al. POD1UM-303/InterAACT 2: a phase III, global, randomized, double-blind study of retifanlimab or placebo plus carboplatin-paclitaxel in patients with locally advanced or metastatic squamous cell anal carcinoma. Front Oncol. 2022;12:935383. doi: 10.3389/fonc.2022.935383
  • Wah Hak CML C, Rullan A, Patin EC, et al. Enhancing anti-tumour innate immunity by targeting the DNA damage response and pattern recognition receptors in combination with radiotherapy. Front Oncol. 2022;12:971959. doi: 10.3389/fonc.2022.971959
  • Levovitz C, Chen D, Ivansson E, et al. TGFβ receptor 1: an immune susceptibility gene in HPV-associated cancer. Cancer Res. 2014;74(23):6833–6844. doi: 10.1158/0008-5472.CAN-14-0602-T
  • Strauss J, Gatti-Mays ME, Cho BC, et al. Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies. J Immunother Cancer. 2020;8(2):e001395. doi: 10.1136/jitc-2020-001395
  • Strauss J, Gatti-Mays M, Cho BC, et al. 957O long-term follow-up of patients (pts) with human papillomavirus (HPV)–associated malignancies treated with bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1. Ann Oncol. 2021;32:S829. doi: 10.1016/j.annonc.2021.08.1342
  • Saúde-Conde R, Parisi A, Giunta EF, et al. The emerging role of immunotherapy in the treatment of anal cancer. Curr Opin Pharmacol. 2022;67:102309. doi: 10.1016/j.coph.2022.102309
  • Strauss J, Floudas C, Sater H, et al. Phase II evaluation of the triple combination of PDS0101, M9241, and bintrafusp alfa in patients with HPV 16 positive malignancies. J Clin Oncol. 2021;392501(15_suppl):10–1200. doi: 10.1200/JCO.2021.39.15_suppl.2501
  • Floudas CS, Strauss J, Redman JM, et al. Phase I evaluation of PRGN-2009 alone and in combination with bintrafusp alfa in patients (pts) with recurrent/metastatic (R/M) HPV-associated cancers (HPV-C). JCO. 2023;41(16_suppl):2628–2628. doi: 10.1200/JCO.2023.41.16_suppl.2628
  • Doran SL, Stevanović S, Adhikary S, et al. T-Cell receptor gene therapy for human papillomavirus-associated epithelial cancers: a first-in-human, phase I/II study. J Clin Oncol. 2019;37(30):2759–2768.
  • Nagarsheth NB, Norberg SM, Sinkoe AL, et al. TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers. Nat Med. 2021;27(3):419–425. doi: 10.1038/s41591-020-01225-1
  • Park JC, Baranda JC, Mita MM, et al. 48MO SQZ-PBMC-HPV-101: preliminary results of a first-in-human, dose-escalation study of a cell-based vaccine in HLA A*02+ patients with recurrent, locally advanced, or metastatic HPV16+ solid tumors. Ann Oncol. 2021;32:S1393. doi: 10.1016/j.annonc.2021.10.065
  • Jimeno A, Baranda J, Iams WT, et al. Phase 1 study to determine the safety and dosing of autologous PBMCs modified to present HPV16 antigens (SQZ-PBMC-HPV) in HLA-A*02+ patients with HPV16+ solid tumors. Invest New Drugs. 2023;41(2):284–295. doi: 10.1007/s10637-023-01342-x
  • Aldersley J, Lorenz DR, Mouw KW, et al. Genomic landscape of primary and recurrent anal squamous cell carcinomas in relation to HPV integration, copy number variation, and DNA damage response genes. Mol Cancer Res. 2021;19(8):1308–1321.
  • Cacheux W, Rouleau E, Briaux A, et al. Mutational analysis of anal cancers demonstrates frequent PIK3CA mutations associated with poor outcome after salvage abdominoperineal resection. Br J Cancer. 2016;114(12):1387–1394. doi: 10.1038/bjc.2016.144
  • Emancipator K, Huang L, Aurora-Garg D, et al. Comparing programmed death ligand 1 scores for predicting pembrolizumab efficacy in head and neck cancer. Mod Pathol. 2021;34(3):532–541. doi: 10.1038/s41379-020-00710-9
  • Mathias-Machado MC, Peixoto RD, Moniz CMV, et al. Biomarkers in anal cancer: Current status in diagnosis, disease progression and therapeutic strategies. Biomedicines. 2022;10(8):2029. doi: 10.3390/biomedicines10082029
  • Salem ME, Puccini A, Grothey A, et al. Landscape of tumor mutation load, mismatch repair deficiency, and PD-L1 expression in a large patient cohort of gastrointestinal cancers. Mol Cancer Res. 2018;16(5):805–812. doi: 10.1158/1541-7786.MCR-17-0735
  • Shao C, Li G, Huang L, et al. Prevalence of high tumor mutational burden and association with survival in patients with less common solid tumors. JAMA Netw Open. 2020;3(10):e2025109. doi: 10.1001/jamanetworkopen.2020.25109
  • Marabelle A, Le DT, Ascierto PA, et al. Efficacy of Pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair–deficient cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2020;38(1):1–10. doi: 10.1200/JCO.19.02105

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.