New approaches in palliative systemic therapy of anal squamous cell carcinoma

Czech version

Authors: R. Lohynská ^1,2; Z. Pechačová ²
Authors‘ workplace: Onkologická klinika 1. LF UK a FTN Praha ¹; Ústav radiační onkologie, 1. LF UK a FN Bulovka, Praha ²
Published in: Klin Onkol 2022; 35(3): 190-194
Category: Review
doi: https://doi.org/10.48095/ccko2022190

Overview

Background: Metastatic and locally recurrent inoperable anal squamous cell carcinoma (ASCC) belong to rare tumours – ASCC accounts for about 2% of gastrointestinal tumours. Synchronous metastatic involvement is usually confirmed in approximately 15% of patients and about 20 % of patients develop relapse in the form of distant metastases after curative treatment. The current standard palliative systemic treatment is a PF regimen composed of 5-fluorouracil (5-FU) with cisplatin (cDDP) or a combination of carboplatin with paclitaxel. Purpose: The aim of this study is to summarize other options for systemic palliative care in ASCC, including the results of relevant clinical trials performed with new or modified regimens. Triple combinations with taxanes have yielded promising treatment results, and in particular, the inclusion of the DCF regimen (cDDP + 5-FU + docetaxel) in first-line treatment results in a significant increase in treatment responses with good treatment tolerance. Another promising option for palliative care is immunotherapy with checkpoint inhibitors PD-1 or PD-L1, which can be successfully used in palliative systemic treatment or in curative regimens. Epidermal growth factor receptor inhibitors remain the subject of research, whose role in the primary or palliative treatment of ASCC is not entirely clear. Conclusion: Compared to standard chemotherapy, available data confirm the treatment outcomes improvement in the use of triple combination DCF with docetaxel or immunotherapy with checkpoint inhibitors in the treatment of metastatic ASCC.

Keywords:

cisplatin – immunotherapy – Chemotherapy – docetaxel – 5-Fluorouracil – anal cancer

Sources

1. Epidemiologie zhoubných nádorů v České republice. [online]. Dostupné z: http: //www.svod.cz.

2. Národní radiologické standardy – radiační onkologie. Věstník Ministerstva zdravotnictví České republiky 2/2016, Praha 2016.

3. Modrá kniha České onkologické společnosti, 28. aktualizace. [online]. Dostupné z: https: //www.linkos.cz/lekar-a-multidisciplinarni-tym/personalizovana-onkologie/modra-kniha-cos/aktualni-vydani-modre- knihy/.

4. Lohynská R, Nýdlová A, Drbohlavová T et al. Hematologická toxicita u IMRT/VMAT v kurativní léčbě análního karcinomu. Klin Onkol 2020; 33 (4): 288–294. doi: 10.14735/amko2020288.

5. Lohynska R, Mazana E, Novakova-Jiresova A et al. Improved survival in patients with FDG-PET/CT-based radiotherapy treatment planning for squamous cell anal cancer. Neoplasma 2020; 67 (5): 1157–1163. doi: 10.4149/neo_2020_191229N1350.

6. Lohynská R, Pechačová Z. Kapecitabin v léčbě análního spinocelulárního karcinomu. Klin Onkol 2022; 35 (1): 38–43. doi: 10.48095/ccko202238.

7. 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.

8. Anal Carcinoma, version 2.2021. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology. [online]. Available from: https: //www.nccn.org/professionals/physician_gls/pdf/anal.pdf

9. Sclafani F, Hesselberg G, Thompson SR et al. Multimodality treatment of oligometastatic anal squamous cell carcinoma: a case series and literature review. J Surg Oncol 2019; 119 (4): 489–496. doi: 10.1002/jso.25 320.

10. Faivre C, Rougier P, Ducreux M et al. Carcinome épidermoïde métastatique de l‘anus: étude rétrospective de l‘efficacité de l‘association de 5-fluoro-uracile en perfusion continue et de cisplatine [5-fluorouracile and cisplatinum combination chemotherapy for metastatic squamous-cell anal cancer]. Bull Cancer 1999; 86 (10): 861–865.

11. Moureau-Zabotto L, Venderely V, Abromwitz L et al. Anal cancer: French Intergroup Clinical Practice Guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SNFCP). Dig Liver Dis 2017; 49 (8): 831–840. doi: 10.1016/j.dld. 2017.05.011.

12. 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.

13. 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.

14. Rao S, Sclafani F, Eng C et al. InterAACT: a multicentre open label randomised phase II advanced anal cancer trial of cisplatin (CDDP) plus 5-fluorouracil (5-FU) vs carboplatin© plus weekly paclitaxel (P) in patients (pts) with inoperable locally recurrent (ILR) or metastatic treatment naive disease – an International Rare Cancers Initiative (IRCI) trial. [online]. Available from: https: //www.annalsofoncology.org/article/S0923-7534 (19) 50413-6/ fulltext.

15. 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; 38 (22): 2510–2518. doi: 10.1200/JCO.19.03266.

16. 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: 10.1177/1758835920975 356.

17. Martini G, Arrichiello G, Borrelli C et al. How I treat anal squamous cell carcinoma. ESMO Open 2020; 4 (Suppl 2): e000711. doi: 10.1136/esmoopen-2020-000711.

18. 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.

19. Yamaura M, Yamada T, Watanabe R et al. Anal canal adenocarcinoma with neuroendocrine features accompanying secondary extramammary Paget disease, successfully treated with modified FOLFOX6: a case report. BMC Cancer 2018; 18 (1): 1142. doi: 10.1186/s12885-018-5084-0.

20. Phuong L, Rajdev L. Immunotherapy in anal cancer. Curr Oncol Rep 2020; 22 (9): 94. doi: 10.1007/s11912-020-00946-3.

21. 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.

22. 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.

23. Kim S, Buecher B, André 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; 20 (1): 352. doi: 10.1186/s12885-020-06841-1.

24. Lukan N, Ströbel P, Willer A et al. Cetuximab-based treatment of metastatic anal cancer: correlation of response with KRAS mutational status. Oncology 2009; 77 (5): 293–299. doi: 10.1159/000259615.

25. Barmettler H, Komminoth P, Schmid M et al. Efficacy of cetuximab in combination with FOLFIRI in a patient with KRAS wild-type metastatic anal cancer. Case Rep Oncol 2012; 5 (2): 428–433. doi: 10.1159/000341371.

26. Leon O, Guren MG, Radu C et al. Phase I study of cetuximab in combination with 5-fluorouracil, mitomycin C and radiotherapy in patients with locally advanced anal cancer. Eur J Cancer 2015; 51 (18): 2740–2746. doi: 10.1016/j.ejca.2015.08.029.

27. 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.

28. 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.

29. Vendrely V, Lemanski C, Gnep K et al. Anti-epidermal growth factor receptor therapy in combination with chemoradiotherapy for the treatment of locally advanced anal canal carcinoma: results of a phase I dose-escalation study with panitumumab (FFCD 0904). Radiother Oncol 2019; 140: 84–89. doi: 10.1016/j.radonc.2019.05.018.

30. 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.