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

Haley Pritchard,Georgios Angelidakis,Harrys A Torres,Deeksha Jandhyala,Jeff Hosry

doi:10.1002/jgh3.12294

Abstract

Background and AimNo 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.MethodsPatients who failed initial DAAs (01/2015–01/2018) were analyzed. Resistance‐associated substitutions to NS5A and NS3 were investigated by population sequencing.ResultsOf 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.ConclusionsThis 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.

Highlights

The rate of sustained virologic response (SVR) to a regimen of at least two direct-acting antiviral (DAA) approaches 95–99% in treatment-naïve patients with Hepatitis C virus (HCV) infection across genotypes 1–6.1 Retreatment can be challenging as exposure to direct-acting antivirals (DAAs) can induce resistance-associated substitutions (RASs) that can persist for many months after initial exposure.[2]
All patients were started on DAA therapy after having their cancer stable or in remission for at least 3–6 months, except in one patient with progressed multiple myeloma who was treated with DAAs to allow access to potentially life-saving investigational cancer therapy
The rates of SVR after first and second DAA salvage therapies in this study, 64%, and 82%, respectively, are slightly lower than the SVR rates of 88–96% after DAA salvage therapy reported in HCV-infected patients without cancer.[3,7,8]

Summary

Introduction

The rate of sustained virologic response (SVR) to a regimen of at least two direct-acting antiviral (DAA) approaches 95–99% in treatment-naïve patients with Hepatitis C virus (HCV) infection across genotypes 1–6.1 Retreatment can be challenging as exposure to DAAs can induce resistance-associated substitutions (RASs) that can persist for many months after initial exposure.[2]. Elimination of HCV from infected cancer patients leads to better hepatic, virologic, and oncologic outcomes.[3,4]. No information exists regarding direct-acting antivirals (DAAs) salvage therapy for Hepatitis C (HCV)-infected patients with any type of cancer. 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.

Methods

Results

Conclusion