314
Views
3
CrossRef citations to date
0
Altmetric
Review

Metastatic or Locally Recurrent Anal Squamous Cell Carcinoma (SCAC): Current Clinical Trial Landscape and Novel Approaches

, &
Pages 2065-2077 | Published online: 21 Jun 2022

References

  • National Comprehensive Cancer Network. Anal carcinoma. Version 2; 2021. Available from: www.nccn.org. Accessed February 23, 2022.
  • Boersma P, Black LI. Human papillomavirus vaccination among adults aged 18−26, 2013−2018. NCHS Data Brief, no 354. Hyattsville, MD: National Center for Health Statistics; 2020.
  • Pingali C, Yankey D, Elam-Evans LD, et al. National, regional, state, and selected local area vaccination coverage among adolescents aged 13–17 years — United States. MMWR Morb Mortal Wkly Rep. 2020;70:1183–1190. doi:10.15585/mmwr.mm7035a1external
  • Leeds IL, Fang SH. Anal cancer and intraepithelial neoplasia screening: a review. World J Gastrointest Surg. 2016;8(1):41–51. doi:10.4240/wjgs.v8.i1.41
  • National Cancer Institute. Surveillance, epidemiology, and end results program. cancer stat facts: anal cancer. Available from: https://seer.cancer.gov/statfacts/html/anus.html. Accessed February 23, 2022.
  • National Cancer Institute. Surveillance, epidemiology, and end results program. anus, anal canal & anorectum stage distribution of SEER incidence cases, 2009–2018. Available from: https://seer.cancer.gov/explorer/application.html?site=111&data_type=1&graph_type=4&compareBy=sex&chk_sex_3=3&chk_sex_2=2&race=1&age_range=1&advopt_precision=1&advopt_display=2. Accessed February 23, 2022.
  • Rogers JE, Eng C. Pharmacotherapy of anal cancer. Drugs. 2017;77:1519–1530. doi:10.1007/s40265-017-0792-3
  • Morris VK, Salem ME, Mimeiri 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
  • Ajani JA, Carrasco CH, Jackson DE, et al. Combination of cisplatin plus fluoropyrimidine chemotherapy effective against liver metastases from carcinoma of the anal canal. Am J Med. 1989;87(2):221–224. doi:10.1016/s0002-9343(89)80702-8
  • Faivre C, Rougier P, Ducreux M, et al. [5-fluorouracile and cisplatinum combination chemotherapy for metastatic squamous-cell anal cancer]. Bull Cancer. 1999;86(10):861–865. Danish.
  • 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
  • Abbas A, Nehme E, Fakih M. Single-agent paclitaxel in advanced anal cancer after failure of cisplatin and 5-fluorouracil chemotherapy. Anticancer Res. 2011;31(12):4637–4640.
  • Boland PM, Wang K, Kohen A. Systemic therapy for advanced anorectal squamous cell carcinomas: a single institutional experience. J Clin Oncol. 2016;34(4):728. doi:10.1200/jco.2016.34.4_suppl.728
  • 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
  • Eng C, Chang GJ, You YN, et al. The role of systemic chemotherapy and multidisciplinary management in improving the overall survival of patients with metastatic squamous cell carcinoma of the anal canal. Oncotarget. 2014;5(22):11133–11142. doi:10.18632/oncotarget.2563
  • 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, Francois E, Andre 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
  • Thomas MK, Pitot HC, Liem A, et al. Dominant role of HPV16 E7 in anal carcinogenesis. Virology. 2011;421(2):114–118. doi:10.1016/j.virol.2011.09.018
  • Marabelle A, Cassier PA, Fakih M, et al. Pembrolizumab for advanced anal squamous cell carcinoma (ASCC): results from the multicohort, phase II KEYNOTE-158 study. J Clin Oncol. 2020;38(4 _suppl):1. doi:10.1200/JCO.19.02105
  • Marabelle A, Cassier PA, Fakih M, et al. Pembrolizumab for previously treated advanced anal squamous cell carcinoma: pooled results from the KEYNOTE-028 and KEYNOTE-158 studies. J Clin Oncol. 2020;38(15):4020. doi:10.1200/JCO.2020.38.15_suppl.4020
  • Rao S, Capdevilla J, Gilbert D, et al. POD1UM-202: phase II study of retifanlimab in patients (pts) with squamous carcinoma of the anal canal (SCAC) who progressed following platinum-based chemotherapy. Ann Oncol. 2020. doi:10.1016/j.annonc.2020.08.2272
  • National Cancer Institute. Nivolumab with or without ipilimumab in treating patients with refractory metastatic anal canal cancer. Clinicaltrials.gov [Internet]. NLM Identifier: NCT02314169. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://clinicaltrials.gov/ct2/show/NCT02314169. Accessed June 13, 2022.
  • 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(4):S412. doi:10.1016/j.annonc.2020.08.514
  • National Comprehensive Cancer Network. Cervical cancer. Version 1; 2022. Available from: www.nccn.org. Accessed February 23, 2022.
  • National Comprehensive Cancer Network. Non-small cell lung cancer. Version 1; 2022. Available from: www.nccn.org. Accessed February 23, 2022.
  • Le LH, Chetty R, Moore MJ, et al. Epidermal growth factor receptor expression in anal canal carcinoma. Am J Clin Pathol. 2005;124(1):20–23. doi:10.1309/X4UADHVN317V2XMW
  • 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
  • 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. 2020;9(3):1008–1016. doi:10.1002/cam4.2722
  • 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. 2021:9e002996. doi:10.1136/jitc-2021-002996
  • Janku F, Hanna GJ, Carvajal RD, et al. First-in-human Phase I study of the bifunctional EGFR/TGFβ fusion protein BCA101 in patients with EGFR-driven advanced solid cancers. J Clin Oncol. 2021;39(15):3074. doi:10.1200/JCO.2021.39.15_suppl.3074
  • Bicara Therapeutics. Study of safety and tolerability of BCA101 monotherapy and in combination therapy in patients with EGFR-driven advanced solid tumors. ClinicalTrials.gov [Internet]. NLM Identifier: NCT04429542. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://clinicaltrials.gov/ct2/show/NCT04429542. Accessed June 13, 2022.
  • Altan M, Patnaik A, Barve MA, et al. NKTR-255 + cetuximab in patients with solid tumors: interim safety and efficacy results from the Phase 1b dose-escalation study. Doi: 10.1136/jitc-2021-SITC2021.957.
  • Nektar Therapeutics. Study of NKTR 255 in combination with cetuximab in solid tumors. ClinicalTrials.gov [Internet]. NLM Identifier: NCT04616196. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://clinicaltrials.gov/ct2/show/NCT04616196. Accessed June 13, 2022.
  • 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
  • Glisson B, Massarelli E, William WN, et al. 1136O - Nivolumab and ISA 101 HPV vaccine in incurable HPV-16+ cancer. Ann Oncol. 2017;28(5):403–404. doi:10.1093/annonc/mdx376.002
  • Morris VK, Jazaeri AA, Westin SN, et al. Phase II trial of MEDI0457 and durvalumab for patients with recurrent/metastatic HPV-associated cancers. J Clin Oncol. 2021;39(15):2595. doi:10.1200/JCO.2021.39.15_suppl.2595
  • Incyte Corporation. Carboplatin-paclitaxel with retifanlimab or placebo in participants with locally advanced or metastatic squamous cell anal carcinoma (POD1UM-303/InterAACT 2). ClinicalTrials.gov [Internet]. NLM Identifier: NCT04472429. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://www.clinicaltrials.gov/ct2/show/NCT04472429. Accessed June 13, 2022.
  • Centre Hospitalier Universitaire de Besancon. Combination of spartalizumab, mDCF and radiotherapy in patients with metastatic squamous cell anal carcinoma (SPARTANA). ClinicalTrials.gov [Internet]. NLM Identifier: NCT04894370. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://clinicaltrials.gov/ct2/show/NCT04894370. Accessed June 13, 2022.
  • National Cancer Institute. EA2176: Phase 3 clinical trial of carboplatin and pacliitaxel ± nivolumab in metastatic anal cancer patients. ClinicalTrials.gov [Internet]. NLM Identifier: NCT04444921. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://clinicaltrials.gov/ct2/show/study/NCT04444921. Accessed June 13, 2022.
  • Kim S, Buecher B, Andre T, et al. Atezolizumab plus modified docetaxel-cisplatin-5-fluorouracil (mDCF) regimen versus mDCF in patients with metastatic or unresectable locally advanced recurrent anal squamous cell carcinoma: a randomized, non-comparative phase II SCARCE GERCOR trial. BMC Cancer. 2020;352(2). doi:10.1186/s12885-020-06841-1
  • Cardiff University. Phase 1b/II trial of pembrolizumab plus IMRT in Stage III/IV carcinoma of anus (CORINTH). ClinicalTrials.gov [Internet]. NLM Identifier: NCT04046133. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://clinicaltrials.gov/ct2/show/NCT04046133. Accessed June 13, 2022.
  • Goethe University. Radiochemotherapy ± durvalumab for locally-advanced anal carcinoma. a multicenter, randomized, Phase II trial of the German anal cancer study group (RADIANCE). ClinicalTrials.gov [Internet]. NLM Identifier: NCT04230759. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://clinicaltrials.gov/ct2/show/NCT04230759. Accessed June 13, 2022.
  • National Cancer Institute. Nivolumab after combined modality therapy in treating patients with high risk Stage II-IIIB anal cancer. ClinicalTrials.gov [Internet]. NLM Identifier: NCT03233711. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://clinicaltrials.gov/ct2/show/NCT03233711. Accessed June 13, 2022.
  • Alqahtani A, Ayesh HSK, Halawani H. PIK3CA gene mutations in solid malignancies: association with clinicopathological parameters and prognosis. Cancrs. 2019;12(1):93. doi:10.3390/cancers12010093
  • 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
  • Mondaca S, Chatila WK, Bastes 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
  • Kura Oncology Inc.. Combination trial of tipifarnib and alpelisib in adult recurrent/ metastatic head and neck squamous cell carcinoma (R/M HNSCC). ClinicalTrials.gov [Internet]. NLM Identifier: NCT04997902. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://clinicaltrials.gov/ct2/show/NCT04997902. Accessed June 13, 2022.
  • Dunn LA, Riaz N, Fury MG, et al. A Phase 1b study of cetuximab and BYL719 (Alpelisib) concurrent with intensity modulated radiation therapy in Stage III-IVB head and neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2020;106(3):564–570. doi:10.1016/j.ijrobp.2019.09.050
  • 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):2–13. doi:10.1186/s41199-018-0030z
  • Parseghian CM, Napolitano S, Loree JM, et al. Mechanisms of innate and acquired resistance to anti-EGFR therapy: a review of current knowledge with a focus on rechallenge therapies. Clin Cancer Res. 2019;25(23):6899–6908. doi:10.1158/1078-0432.CCR-19-0823
  • National Cancer Institute. HPV vaccine PRGN-2009 alone or in combination with anti-PDL1/TGF-beta trap (M7824) in subjects with HPV associated cancers. ClinicalTrials.gov. NLM Identifier: NCT04432597. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://clinicaltrials.gov/ct2/show/NCT04432597. Accessed June 13, 2022.
  • Cimino SK, Ciombor KK, Chakravarthy AB, et al. Safety considerations with new treatment regimens for anal cancer. Expert Opin Drug Saf. 2021;20(8):889–902. doi:10.1080/14740338.2021.1915281
  • Strauss J, Gatti-Mays M, 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:e001395. doi:10.1136/jitc-2020-001395
  • National Cancer Institute. Combination immunotherapy in subjects with advanced HPV associated malignancies. ClinicalTrials.gov [Internet]. NLM Identifier: NCT04287868. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://clinicaltrials.gov/ct2/show/NCT04287868. Accessed June 13, 2022.
  • National Cancer Institute. DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 and durvalumab in treating patients with recurrent or metastatic human papillomavirus associated cancers. ClinicalTrials.gov [Internet]. NLM Identifier: NCT03439085. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://clinicaltrials.gov/ct2/show/NCT03439085. Accessed June 13, 2022.
  • ClinicalTrials.gov. Centre hospitalier universitaire de besancon combination of UCPVax vaccine and atezolizumab for the treatment of human papillomavirus positive cancers (VolATIL) (VolATIL). NLM Identifier: NCT03946358. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://clinicaltrials.gov/ct2/show/NCT03946358. Accessed June 13, 2022.
  • Turnstone Biologics, Corp. This is a trial of MG1-E6E7 with Ad-E6E7 and atezolizumab in patients with HPV associated cancers (Kingfisher). ClinicalTrials.gov [Internet]. NLM Identifier: NCT03618953. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://clinicaltrials.gov/ct2/show/NCT03618953. Accessed June 13, 2022.
  • SQZ Biotechnologies. Study of SQZ-PBMC-HPV in patients with HPV16+ recurrent, locally advanced or metastatic solid tumors. ClinicalTrials.gov [Internet]. NLM Identifier: NCT04084951. Bethesda (MD): National Library of Medicine (US); 2000. Available from: https://clinicaltrials.gov/ct2/show/NCT04084951. Accessed June 13, 2022.
  • Bernanrd-Tessier A, Jeannot E, Guenat D, et al. Clinical validity of HPV circulating tumor DNA in advanced anal carcinoma: an ancillary study to the epitopes-HPV02 trial. Clin Cancer Res. 2019;25(7):2109–2115. doi:10.1158/1078-0432.CCR-18-2984
  • Morris VK, Thomas MK, Pitot HC, Liem A, Lambert PF. Circulating tumor DNA in advanced anal cancer: a blood biomarker goes viral. Clin Cancer Res. 2019;25(7):2030–2032. doi:10.1158/1078-0432.CCR-18-3982
  • Cabel L, Jeannot E, Bieche I, et al. Prognostic impact of residual HPV ctDNA detection after chemoradiotherapy for anal squamous cell carcinoma. Clin Cancer Res. 2018;24(22):5767–5771. doi:10.1158/1078-0432.CCR-18-0922
  • Lefèvre AC, Pallisgaard N, Kronborg C, et al. The clinical value of measuring circulating HPV DNA during chemo-radiotherapy in squamous cell carcinoma of the anus. Cancers. 2021;13(10):2451. doi:10.3390/cancers13102451