Prospective study of biomarkers in squamous cell carcinoma of the anal canal (SCCAC) and their influence on treatment outcomes: Final results.

Abstract

3577 Background: While chemoradiation (CRT) is a curative treatment for SCCAC, many patients (pts) present primary resistance. As a rare tumor, the predictors of response in this setting remain unknown. Methods: Prospective cohort study aimed to evaluate predictive biomarkers (Ki-67, PD-L1, Human papillomavirus (HPV), HIV status and mutations in tumoral DNA) associated with complete response (CR) following standard CRT for localized SCCAC. Eligible pts had T2-4/N0-3/M0 disease and were candidates to standard CRT. CR at 6 months (m) measured by RECIST 1.1 was the primary endpoint. DNA mutations were analyzed by next-generation (NGS) TruSight Tumor26 panel. HPV positivity was tested by PapilloCheck Test. KI-67 and PD-L1 were evaluated by immunohistochemistry. Results: 78 pts were recruited from Jan/2011 to Dec/2015. 75 were evaluable for response. Median age 57 years; 49 (65%) were stage III, and 9 (12%) were HIV+. At 6m 47 (62.7%) had CR, 18 (24%) partial response (PR) and 10 (13.3%) disease progression. HPV was evaluated in 67 and found in 47 (70.1%), the majority HPV16. PD-L1 was tested in 61, 10 (16.4%) had > 1% positive expression. Ki-67 was performed in 65, a median was 50% (1-90%) per patient. Clinical stage, HIV status, median KI-67, HPV and PD-L1 positivity, and treatment interruption were tested as predictive factors of CR in 6m by logistic regression. On multivariable analyses, ECII patients were 4.7 more likely to achieve CR than ECIII (OR 4.70 CI95%1.36-16.30; p = 0.015). HIV was borderline significant (OR 2.53 CI95% 0.9-7.1; p = 0.079). Analyzing the patients with PR and CR HIV+ was significantly associated with poor response. Patients HIV- were 5.7 more likely to achieve CR or PR (OR 5.72 CI95%2.5-13.0; p < 0.001). 25 patients had tumor samples proper for NGS, 17 had at least one pathogenic mutation. The most common mutated genes were PIK3CA and MET in 6. There was no differences in CR rates according to MET (50% vs 47.3%, p = 1) or PIK3CA (33.3% vs 47.3%, p = 0.6) mutation status. TP53 codon 72 polymorphism was present in 72% (n = 18) and was not associated with CR (44% VS 57%, p = 0.6). Conclusions: Our study suggests that HIV+ pts are less responsive to CRT.