Is there still a role for talimogene laherparepvec (T-VEC) in advanced melanoma? An indirect efficacy comparison of T-VEC plus ipilimumab combination therapy versus T-VEC alone as salvage therapy in unresectable metastatic melanoma

ABSTRACT

Background

Talimogene laherparepvec (T-VEC) improves overall survival (OS) in unresectable stage IIIB/C-IV melanoma T-VEC may have synergistic effects with CTLA-4 inhibitors In the absence of a trial comparing T-VEC and ipilimumab (T-VEC + IPI) to T-VEC, we applied a novel indirect comparison method using extrapolated OS curves to estimate OS outcomes in a simulated trial comparing both regimens in stage IIIB/C-IV unresectable melanoma.

Research Design and Methods

Two trials with extractable OS curves for a T-VEC versus T-VEC + IPI comparison were identified. Outcomes were adjusted for heterogeneity in prognostic factors using a calculated adjustment factor. T-VEC and adjusted/unadjusted T-VEC+IPI curves were plotted with 95% CIs.

Results

Unadjusted indirect OS comparison of T-VEC versus T-VEC + IPI revealed no significant difference up to 15 months. Extrapolation beyond 15 months showed significant survival benefits for T-VEC + IPI over T-VEC, confirmed in adjusted analyses. The expected OS percentage at 48 months is 32.0% (95% CI = 26.6–37.3) for T-VEC, 60.0% (95% CI = 46.2–69.1) for unadjusted, and 81.1% (95% CI = 72.3–85.9) for adjusted T-VEC + IPI.

Conclusions

Our novel indirect comparison suggests that T-VEC + IPI may demonstrate a significantly improved OS versus T-VEC alone. Findings may portend a possible role for the addition of T-VEC to advanced melanoma treatment regimens in select patients as salvage therapy.

KEYWORDS:

• Talimogene laherparepvec
• T-VEC
• advanced melanoma
• indirect comparison
• ipilimumab
• CTLA-4 inhibitor

Declaration of Interests

Ivo Abraham is the Quantitative Methods Editor for JAMA Dermatology and the Deputy Editor in Chief of the Journal of Medical Economics. He is joint equity owner in Matrix45. By company policy, owners and employees are prohibited from owning equity in client and sponsor organizations (except through mutual funds or other independently administered collective investment instruments), contracting independently with client and sponsor organizations, or receive compensation independently from such organizations. Matrix45 provides similar services to other biopharmaceutical, diagnostics, and medical device companies on a non-exclusivity basis. Clara Curiel has served on the advisory board of Helsinn Therapeutics, Inc and Bristol-Myers Squibb.

The authors have no other relevant affiliations or financial involvement with an organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Author contributions

Mohammad Fazel, MD, PharmD: conception, design, interpretation of data, drafting and revision of paper content; Neda AlRawashdh PharmD: MSdesign, analysis of data, interpretation of data, drafting and revision of paper contents; Ahmad Alamer, PharmD: design, analysis of data, interpretation of data, drafting and revision of paper contents; Clara Curiel-Lewandrowski, MD: interpretation of data, revision of paper contents; Ivo Abraham, PhD: design, analysis of data, interpretation of data, revision of paper contents. All authors agree to be accountable for all aspects of the work.

Additional information

Funding

This paper is not funded.