Salvage therapy in cancer patients with hepatitis C without sustained virologic response after direct-acting antivirals-A prospective study

Background and Aim No information exists regarding direct-acting antivirals (DAAs) salvage therapy for Hepatitis C (HCV)-infected patients with any type of cancer. We prospectively evaluated the safety and efficacy (SVR12) of salvage therapy in these patients. Methods Patients who failed initial DAAs (01/2015-01/2018) were analyzed. Resistance-associated substitutions to NS5A and NS3 were investigated by population sequencing. Results Of 164 patients enrolled, 16 (10%) experienced treatment failure. Of these, 11 patients received salvage therapy. The majority (91%) were men; 55% had genotype 1a, 45% had cirrhosis, and 45% had hepatocellular carcinoma. Four patients failed the first salvage therapy, and two of them required a second salvage therapy. Overall, 9 of 11 (82%) patients achieved SVR12. All four patients treated with sofosbuvir/velpatasvir/voxilaprevir (+/- ribavirin) achieved SVR12. The presence of resistance-associated substitutions did not impact response. Seven patients developed grade 1/2 adverse events. No patient had grade 3/4 adverse events. No patient required interruption of DAA therapy because of clinical or laboratory abnormalities. Conclusions This is the first prospective study in HCV-infected cancer patients failing DAAs. The efficacy of salvage therapy in this group appears to be lower than previously reported in non-cancer patients, but better response rates are observed with newer regimens. Salvage therapy is associated with minimal toxicity.