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 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 April 2019 -- Source: Scopus |
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