FOLFCIS treatment and genomic correlates of response in advanced anal squamous cell cancer Journal Article

Authors: Mondaca, S.; Chatila, W. K.; Bates, D.; Hechtman, J. F.; Cercek, A.; Segal, N. H.; Stadler, Z. K.; Varghese, A. M.; Kundra, R.; Capanu, M.; Shia, J.; Schultz, N.; Saltz, L.; Yaeger, R.
Article Title: FOLFCIS treatment and genomic correlates of response in advanced anal squamous cell cancer
Abstract: In a series of 53 patients with advanced anal squamous cell cancer, we demonstrate that a modified 5-fluorouracil and cisplatin schedule (FOLFCIS) with lower dose, more frequent administration of cisplatin is effective and well-tolerated. This regimen should be considered a standard treatment option. Human papillomavirus-negative anal squamous cell cancers were less sensitive to platinum-based therapy and exhibited a distinct molecular profile. Background: Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC. Patients and Methods: We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers. Results: Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations. Conclusions: FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients. © 2018 The Authors
Keywords: cisplatin; platinum; 5-fluorouracil; human papillomavirus; massively parallel sequencing
Journal Title: Clinical Colorectal Cancer
Volume: 18
Issue: 1
ISSN: 1533-0028
Publisher: Elsevier Inc.  
Date Published: 2019-03-01
Start Page: e39
End Page: e52
Language: English
DOI: 10.1016/j.clcc.2018.09.005
PROVIDER: scopus
PMCID: PMC6428631
PUBMED: 30316684
Notes: Article -- Export Date: 1 April 2019 -- Source: Scopus
Citation Impact
MSK Authors
  1. Leonard B Saltz
    671 Saltz
  2. Neil Howard Segal
    141 Segal
  3. Zsofia Kinga Stadler
    209 Stadler
  4. Marinela Capanu
    265 Capanu
  5. Jinru Shia
    535 Shia
  6. Rona Denit Yaeger
    124 Yaeger
  7. Nikolaus D Schultz
    269 Schultz
  8. Jaclyn Frances Hechtman
    164 Hechtman
  9. Ritika   Kundra
    33 Kundra
  10. Walid Khaled Chatila
    27 Chatila
  11. David Dawson Bartlett Bates
    14 Bates